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The genetic analysis of factors influencing the lethality associated with the scute inversions of Drosophila… Johnson, Carey 1981

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THE GENETIC ANALYSIS OF FACTORS INFLUENCING THE LETHALITY ASSOCIATED WITH THE SCUTE INVERSIONS OF DROSOPHILA MELANOGASTER.  by  CAREY BSc,  JOHNSON  U n i v e r s i t y o f B r i t i s h Columbia, 1978  A THESIS SUBMITTED I N P A R T I A L FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE  I n t h e Department o f Zoology '  We a c c e p t t h i s t h e s i s a s conforming to the required  standard  THE UNIVERSITY OF B R I T I S H COLUMBIA May, ©  1981  Carey Johnson, 1981  In p r e s e n t i n g  t h i s t h e s i s i n p a r t i a l f u l f i l m e n t o f the  requirements f o r an advanced degree a t the U n i v e r s i t y o f B r i t i s h Columbia, I agree t h a t  the L i b r a r y s h a l l make  it  and study.  f r e e l y a v a i l a b l e f o r reference  I further  agree t h a t p e r m i s s i o n f o r e x t e n s i v e copying o f t h i s t h e s i s f o r s c h o l a r l y purposes may be granted by the head o f my department o r by h i s o r her r e p r e s e n t a t i v e s . understood t h a t  copying or p u b l i c a t i o n of t h i s t h e s i s  f o r f i n a n c i a l gain  s h a l l not be allowed without my  permission.  Department o f The U n i v e r s i t y o f B r i t i s h 2075 Wesbrook P l a c e Vancouver, Canada V6T 1W5 Date  Iti s  3  s  Columbia  written  i  ABSTRACT  I t has been p r e v i o u s l y e s t a b l i s h e d t h a t i n v i a b i l i t y i s associated mosome. lethality  w i t h X/0 m a l e s c a r r y i n g a s c u t e  Explanations  explanation  chro-  o f t h i s phenomenon s u g g e s t t h a t t h e  may "be due t o a p o s i t i o n e f f e c t s u p p r e s s i o n  t h e rRNA c i s t r o n s .  for  inversion X  This  thesis provides  o f t h e s c u t e X/0 l e t h a l i t y  the primary f u n c t i o n of the scute  of  an a l t e r n a t i v e  and p r o v i d e s  support  locus.  These s t u d i e s i n d i c a t e t h a t t h e l e t h a l i t y  associated  w i t h t h e s c u t e X/0 g e n o t y p e i s c o n d i t i o n a l a n d d e p e n d e n t upon t h e p a r e n t a l  o r i g i n o f t h e X chromosome.  experiments i n d i c a t e that the l e t h a l i t y d i s f u n c t i o n o f the scute trons.  Numerous  r e s u l t s from a  l o c u s r a t h e r t h a n t h e rRNA  cis-  ii  TABLE OF CONTENTS Page ABSTRACT  i  TABLE OF CONTENTS  i i  L I S T OF TABLES  i  L I S T OF FIGURES  i  i iv  ACKNOWLEDGEMENT  '."  v i  1 .  GENERAL INTRODUCTION  5^-  MATERIALS AND METHODS RESULTS C h a p t e r 1.  Parental I. II.  C h a p t e r 2.  Source  Effect:  Paternally derived  X  62.  Maternally  X  78.  X/O V i a b i l i t y  derived  o f Recombinant 88.  Scute Inversions C h a p t e r 3*  Maternal Effects of  Inversion  Heterozygotes M o d i f i c a t i o n o f X/0 V i a b i l i t y b y X-chromosome H e t e r o c h r o m a t i c D u p l i c a t i o n a n d A l t e r e d YChromosomes  100.  C h a p t e r 5-  The Compound X E f f e c t  121.  C h a p t e r 6.  The T e m p e r a t u r e  127.  C h a p t e r 7-  The D e v e l o p m e n t a l  C h a p t e r 8.  The B r i s t l e  C h a p t e r 4.  DISCUSSION BIBLIOGRAPHY  Effect Delay  Phenotype  108.  136. 1-55• 165. 183-  iii  L I S T OF TABLES  TABLE  PAGE  1.  M u t a t i o n s used as g e n e t i c markers  2.  Paternally  d e r i v e d X-chromosome:  lethality  55' Scute  X/0 65 •  "."  3.  The s c u t e m a t e r n a l e f f e c t  ^«  X/0 m a l e v i a b i l i t y  79-  i n s c u t e X-chromosome 89.  recombinants 5.  X/0 v i a b i l i t y  6.  Alteration of paternal  from heterozygous scute females. e f f e c t by  duplications 109 •  and a l t e r e d Y ' s ( 7.  sc A x  x  C(1)RM yw/Dp )  Alteration of paternal  e f f e c t by  duplications 110.,  and a l t e r e d Y ' s ( C(1)RM yvpn/Dp 8.  101.  sc /Y x  x  A l t e r a t i o n o f m a t e r n a l e f f e c t by  ) duplications  and a l t e r e d Y ' s  11?.  9.  The compound-X e f f e c t . . . .  122.  10.  The p a t e r n a l  temperature  effect  128.  11.  The m a t e r n a l t e m p e r a t u r e  effect  133*  12.  The d e v e l o p m e n t a l d e l a y  138.  13.  Microchaetae frequency  156.  1^.  Scutellar bristle  l6l.  frequency  iv  L I S T OF FIGURES  FIGURE  1.  PAGE  Diagramatic representation v e r s i o n chromosomes  o f the scute i n -  56.  2.  D e s c r i p t i o n and s o u r c e o f s p e c i a l chromosomes...  58.  3.  M a t i n g scheme f o r g e n e r a t i n g s c u t e X / 0 m a l e s with d i f f e r e n t parental origins of the X-chromosome  63-  ^'  X/0 tal  5-  X/0 v i a b i l i t y o f s c u t e r e c o m b i n a n t X-chromosomes o f d i f f e r e n t p a r e n t a l o r i g i n  91-  V i a b i l i t y o f scute i n v e r s i o n X/0 males d e r i v i n g t h e i r X-chromosome f r o m h e t e r o z y g o u s and homozygous f e m a l e s o r h e m i z y g o u s m a l e s  10k.  E f f e c t o f Ybb", an a d d i t i o n a l s c u t e l o c u s , and h e t e r o c h r o m a t i c d u p l i c a t i o n s on t h e v i a b i l i t y o f scute X/0 males  111.  6.  7.  I 8.  v i a b i l i t y associated with d i f f e r e n t pareni n h e r i t a n c e o f t h e s c u t e X-chromosomes  :  Paternal sion  i n h e r i t a n c e o f scute  inver-  E f f e c t o f Ybb~, an a d d i t i o n a l s c u t e l o c u s , and h e t e r o c h r o m a t i c d u p l i c a t i o n s on t h e v i a b i l i t y o f scute X/0 males II  :  Maternal i n h e r i t a n c e o f scute  81.  118.  inver-  sion 9.  The compound-X e f f e c t  12^.  10.  The t e m p e r a t u r e e f f e c t  130.  I 11.  P a t e r n a l l y i n h e r i t e d X-chromosome  The t e m p e r a t u r e e f f e c t I I : M a t e r n a l l y i n h e r i t e d X-chromosome  I3A-.  V  FIGURE  12..  .  :  Raw d a t a  The d e v e l o p m e n t a l d e l a y . II  :  Cumulative percentage recovery p l o t s ' a)  lk.  x  C ( 1 ) R M yw/O  1^2.  A  x  C ( 1 ) R M yw/Y  1^3-  8  b)  s c  c)  sc /sc  8  x  X-Y/O  1^.  d)  sc /sc  8  x  X-Y/Y  1^5.  8  8  8  s  P r o b i t s analysis of data a)  sc /Y 8  x  C ( 1 ) R M yw/O  ^ '  b)  sc /Y  x  C ( 1 ) R M yw/Y  1^8.  c)  sc /sc  8  x  X-Y/O  1^9-  d)  sc /sc  8  x  X-Y/Y  150.  8  8  8  B r i s t l e frequency i n a s e r i e s of scute s i o n X/O m a l e s . I  16.  sc /Y  The d e v e l o p m e n t a l d e l a y . Ill  15-  139-  The d e v e l o p m e n t a l d e l a y I  13.  PAGE  :  inver-  The m i c r o c h a e t a e  158.  B r i s t l e frequency i n a series of scute invers i o n X/0 m a l e s . II  :  The s c u t e l l a r s  163.  vi  ACKNOWLEDGMENT  I would  like  t o t h a n k D r . D a v i d G. H o l m f o r h i s s u p -  p o r t and c o n t i n u i n g  i n t e r e s t i n these p r o j e c t s .  I must  e x p r e s s my s i n c e r e g r a t i t u d e t o Bob D e v l i n , who i n s p i r e d many o f t h e r e s e a r c h technical assistance.  s t r a t e g i e s and p r o v i d e d A l s o , I would  like  valuable  t o e x t e n d my  thanks t o a l l those people associated w i t h the f l y labs who  stimulated discussions a t our conference  Finally,  I would  like  sessions.  t o t h a n k S u z a n n e N o b l e , who c o n t r i -  buted g r e a t l y t o the p r e p a r a t i o n  of this  manuscript.  1.  INTRODUCTION  I t has profoundly  l o n g "been e s t a b l i s h e d t h a t a g e n e ' s e x p r e s s i o n i n f l u e n c e d by  i t s neighboring  genetic  In prokaryotes,  the p o l a r i t y of the g e n e t i c  that a specific  s p a c i a l arrangement m a i n t a i n s  efficiency.  genes i s not  information  infers  maximum f u n c t i o n a l  so o b v i o u s l y p o l a r and  have been c o m p e l l e d t o study g e n e t i c refined level. the  environment.  I n t h e more c o m p l e x e u k a r y o t i c genome, t h e  ment o f a d j a c e n t  U n t i l recent  arrange-  researchers  i n t e r a c t i o n s at a l e s s  advances i n b i o c h e m i c a l  genetics,  s t u d i e s o f e u k a r y o t i c gene e x p r e s s i o n h a v e i n v o l v e d  mental problems i n the  is  funda-  o r g a n i z a t i o n of the h e r e d i t a r y m a t e r i a l .  I n D r o s o p h i l a m e l a n o g a s t e r , t h e phenomenon o f p o s i t i o n e f f e c t has  provided  gene e x p r e s s i o n .  numerous r e s e a r c h  strategies involved with  P o s i t i o n e f f e c t s are d e f i n e d as a l l those  s i t u a t i o n s where s t a n d a r d  genetic  expression  i s disturbed  owing to changes i n chromosomal arrangement. first  coined  the phrase " p o s i t i o n e f f e c t "  s t a b l e phenomenon i n v o l v i n g t h e B a r s t u d i e s i n d i c a t e d t h a t f o r two phenotypic on t h e  e f f e c t was  X-chromosomes ( t r a n s ) .  i n reference  (B) m u t a n t l o c u s .  two  alleles  opposed to b e i n g  This cis-dominant  on  (1925)  to  a  His  d i f f e r e n t a l l e l e s o f B,  f a r g r e a t e r when t h e  same chromosome ( c i s ) as  Sturtevant  the were  separate  phenomenon  was  t e r m e d £3 o r s t a b l e - t y p e p o s i t i o n e f f e c t as t h e m u t a n t p h e n o t y p e was  s t a b l e or c o n s i s t e n t throughout the a f f e c t e d  indi-  2.  victual. A second type fied  o f p o s i t i o n e f f e c t t h a t has been  i s termed V-type  position effect.  associated with a variegated  Morgan  types  T h i s a n o m a l y was f i r s t  (1923).  who d e s c r i b e d  T h i s phenomenon i s  (V) o r m o s a i c e x p r e s s i o n  m u t a n t gene o w i n g t o s p e c i f i c ments.  identi-  o f chromosomal  of a  rearrange-  r e p o r t e d by B r i d g e s and  a weak e x p r e s s i o n  o f the  plexus  ( p x ) p h e n o t y p e a s s o c i a t e d w i t h a chromosome r e a r r a n g e m e n t . Sturtevant  (1925)  commented t h a t t h e i n c o m p l e t e  o f t h e p_x m u t a t i o n px  +  c o u l d be a r e s u l t o f t h e p r o x i m i t y o f t h e  locus to thebreakpoints  speculated  t h a t the p a r t i a l  o f t h erearrangement. expression  f u n c t i o n o f the a l t e r e d g e n e t i c vicinity  expression  o f the breakpoint.  He f u r t h e r  o f t h e l o c u s was a  environment i n the  Thus, S t u r t e v a n t  immediate  first  proposed  t h e a s s o c i a t i o n o f chromosomal r e a r r a n g e m e n t s w i t h p o s i t i o n effect variegation. The  discovery that X - r a d i a t i o n induced  chromosomal r e a r -  r a n g e m e n t s p r o v e d t o be a m a j o r i m p e t u s t o t h e s t u d i e s o f position effect generation to  X-rays.  (Muller,  1930a).  Muller  o f "eversporting displacements" He o b s e r v e d t h e i n c o m p l e t e  (y;) a n d a c h a e t e  (1930b)  reported the  i nstocks  expression  of yellow  (ac) and a t t r i b u t e d t h e r e s u l t t o a  gene i n s t a b i l i t y .  Patterson  (1932c)  exposed  somatic  a l s o u s e d X - r a y s t o gen-  e r a t e a s t o c k v a r i e g a t i n g f o r numerous genes n e a r t h e t i p o f t h e X-chromosome.  He e x p l a i n e d  t i o n as a r e s u l t o f a s p e c i f i c  t h i s multiple-mutant somatic  condi-  l o s s of "unstable"  3-  genetic was  material.  associated  to the  M o r e o v e r , he  f r a g m e n t may  be  Patterson  l o s t during  s m a l l X-chromosome r e g i o n .  mosaic  The  s o m a t o g e n e s i s and  coexistence  Gay  (1933a)  first  the  of the d e f i c i e n t  engaged i n s t u d i e s  or  (Gowan and  Gay,  1933a,b).  The  t o Y-chromosomal  white-mottled stocks  X-chromosomal i n v e r s i o n s w i t h b r e a k p o i n t s  validity  (w)  locus.  of Patterson's  somatic c e l l  This  i n the  be  (1932c)  t h i s disturbance Gay,  carrying  proximity  generated from the  i n the  vicinity  of the  somehow i n f l u e n c e s n o r m a l gene  the  aneuploid inversion  Gay  t h a t t h e m e c h a n i s m o f v a r i e g a t i o n must i n v o l v e t h e hereditary material  generated  as  as v i a b l e  V i e w i n g t h i s e v i d e n c e , Gowan and  was  material  f a c t greatly jeopardized  theory  l i n e s could not  cells.  (Gowan and  the  phenotypes.  t h e s e a u t h o r s were c y t o l o g i c a l l y c h a r a c t e r i z e d  white  on  e x p e r i m e n t s s u g g e s t e d t h a t t h e phenomenon  s e n s i t i v e t o t e m p e r a t u r e c h a n g e s and  of the  a  phenotype.  These o r i g i n a l  bearing  as  deficient for  modifying factors involved with variegating  of the  trans-  the normal c e l l s would r e s u l t i n a v a r i e g a t e d  Gowan and  by  material  suggested t h a t the  c o n s e q u e n c e , a l l d e s c e n d a n t c e l l s w o u l d be  c e l l s with  phenotype  w i t h a t r a n s l o c a t i o n o f X-chromosomal  f o u r t h chromosome.  located  observed t h a t the  theorized disruption  gene  and  expression  193^)•  A f t e r t h e s e s t u d i e s , d a t a were a c c u m u l a t e d r a p i d l y concerning  the  S h o r t l y , an  factors involved with position effect variegation. a b u n d a n c e o f v a r i e g a t i n g g e n e s were  identified  k.  and,  i n a l l c a s e s , t h e r e l a t i v e p o s i t i o n o f t h e gene h a d "been  altered with respect to neighboring l o c i . observed  The phenomenon was  i n many t y p e s o f c h r o m o s o m a l r e a r r a n g e m e n t s s u c h a s  i n v e r s i o n s , d u p l i c a t i o n s and t r a n s l o c a t i o n s ( D u b i n i n and Siderov,  1935;  Panshin,  1935;  Goldschmidt  1939).  et al.,  T h i s d i s c o v e r y l e d t o many new t h e o r i e s c o n c e r n e d i n t e r p r e t a t i o n o f t h e phenomenon o f p o s i t i o n Patterson  (1931c),  Stern  (1935)  tained the suggestion that l o c i  with the  effect.  (1936)  and S c h u l t z  i ntheproximity o f rearrange-  ment b r e a k p o i n t s w e r e somehow s o m a t i c a l l y u n s t a b l e .  Citing  o b v i o u s p r o b l e m s w i t h t h i s t h e o r y , many o t h e r a u t h o r s t h a t t h e mosaicism  was a r e s u l t  T h e s e two a l t e r n a t i v e for  G r u n e b e r g , 1937;  E p h r u s s i and S u t t o n , a number o f a u t h o r s  19^]4;  193^;  S u r r a r r e r , 1938)  e x p l a n a t i o n s remained w e l l  schools o f thought  into  (Gowan a n d Gay,  (Stern et a l . ,  Gersh and E p h r u s s i ,  evidence  19^5;  19^6).  Finally,  s o u g h t t o show t h a t t h e v a r i e g a t i n g p h e n o -  t y p e s c o u l d be r e v e r s e d b y r e i n v e r t i n g t h e w h i t e - m o t t l e d o r roughest  (rst) inversions.  T h i s would s t r o n g l y imply  that  t h e gene i t s e l f h a d n o t b e e n p e r m a n e n t l y a l t e r e d a n d t h e mut a n t phenotype r e s u l t e d from t h e d i s t u r b e d environment. Panshin  (1938)  r e p o r t e d t h e "complete r e v e r s a l "  o f the white-  m o t t l e d p h e n o t y p e a n d t h i s o b s e r v a t i o n was s u p p o r t e d cytological identification of thereinversion.  .  supported  many y e a r s a s i n v e s t i g a t o r s c o n t i n u e d t o p r o d u c e  supporting both  reasoned  o f t h e new e n v i r o n m e n t  w h i c h t h e n o r m a l gene h a d b e e n p l a c e d Demerec a n d S l i z y n s k a , 1937;  main-  by t h e  Similar re-  5-  s u i t s f o r the Gradually,  r s t inversions  were r e p o r t e d b y Kaufmann  e v i d e n c e mounted s u p p o r t i n g the  s o m a t i c gene s t a -  bility  h y p o t h e s i s a n d i t h a s now become a n a c c e p t e d  of the  position-effect variegation  Gersh,  1957)•  Previous t o t h i s conclusion, on  the  association  o f the  model ( L e w i s ,  1936;  apparent that  "inert"  a r e s u l t o f the  variegating  1937).  i n t o the  effect variegation  I t s o o n became  prox-  processes involved DNA w i t h  with  the  compaction  respect to position-  ( P r o k o f y e v a - B e l g o v s k a y a , 19^7;  19^9;  Gersh,  1959)•  variegating  position effects.  t y p e gene m u s t c o e x i s t  on the  clones o f somatic c e l l s . the  b o t h n o r m a l and mutant  I n contrast,  allow  and mutant c e l l l i n e s .  w i l d type a l l e l e ,  wild  same chromosome ( c i s ) a s t h e  m u t a n t gene l i n k e d t o t h e  T h i s s i t u a t i o n does not  f o r a l l true  The r e a r r a n g e m e n t a n d t h e  p r o d u c t i o n o f mosaic t i s s u e r e q u i r e s  mal  primarily  T h i s evidence prompted  A c i s - t r a n s r e l a t i o n s h i p c a n be e s t a b l i s h e d  involves  por-  1936;  r e l o c a t i o n o f euchromatic genes i n t o the  or h e t e r o c h r o m a t i z a t i o n o f the  Spofford,  Dubinin,  p o s i t i o n e f f e c t s were  imity o f a heterochromatic region. many s t u d i e s  with  or heterochromatic  Demerec a n d S l i z y n s k a , the  1950;  gene e x p r e s s i o n  t i o n s o f chromosomes ( D o b z h a n s k y , 1936; Schultz,  component  many a u t h o r s h a d commented  variegated  rearrangements i n v o l v i n g the  (19^2).  f o r the  the.trans rearranged  arrangement chromosome.  production o f both nor-  The c i s - t r a n s t e s t i n v o l v e s  a^, a mutant a l l e l e ,  a  a, a b r e a k p o i n t , bp,  6.  and  a. n o r m a l chromosome, hp .  The a  h p / a hp  individual  e x h i b i t v a r i e g a t i o n f o r the a l o c u s as t h ew i l d type and  thebreakpoint  a r e c i s t o each other.  An a  d i v i d u a l has t h e t r a n s arrangement and normal  will  allele  bp / a bp i n -  complementation  r e s u l t s i na w i l d phenotype. Experiments i n v o l v e d w i t h r e v e r t i n g the mosaic phenotype s t r o n g l y i n d i c a t e t h a t t h e change i s b r o u g h t about o n l y b y f u r t h e r chromosome b r e a k a g e . and  Novitski  (1961)  Gruneberg  have a l l r e c o v e r e d  (1937)>  Kaufmann  (19^2)  r e v e r s i o n s o f the r s t  phenotype by i r r a d i a t i n g r s t h e t e r o z y g o t e s .  These  authors  h a v e shown . t h a t t h e r e v e r s i o n s f r o m t h e m u t a n t p h e n o t y p e were all  a c c o m p a n i e d b y new r e a r r a n g e m e n t s w h i c h t r a n s f e r r e d a  great  d e a l o f the d i s p l a c e d heterochromatin  t o a new p o s i t i o n .  O t h e r a u t h o r s h a v e shown t h a t t h e i n c o m p l e t e c y t o l o g i c a l r e v e r s i o n c a n r e s u l t i n a change i n e x p r e s s i o n phenotype i n the  1950)•  d i r e c t i o n o f w i l d type  of the variegated  (Hinton and Goodsmith,  A t t e m p t s t o p r o d u c e r e v e r t a n t s o f some v a r i e g a t i n g  systems such as scute and M u l l e r ,  (.sc)  have been u n s u c c e s s f u l  (Raffel  19^0).  Numerous f a c t o r s a r e known t o m o d i f y t h e e x p r e s s i o n o f position-effect variegation. reported by  Gowan a n d G a y  (1933a)  first  t h a t v a r i e g a t i o n f o r t h e w h i t e gene was s u p p r e s s e d  a n e x t r a Y-chromosome.  A variety of studies investigating  t h e u b i q u i t y o f t h i s phenomenon h a v e r e v e a l e d  that  variega-  t i o n i s d e c r e a s e d a s t h e number o f Y-chromosomes i s i n c r e a s e d . Experiments generating  X/0 m a l e s h a v e s u g g e s t e d t h a t t h e mu-  7-  (X/0  tant progression  o f t h e Y - c h r o m o s o m e (Gowan a n d Gay,  modifying feature Schultz,  1936;  i sa direct result ofa  > X / Y > X/Y/Y)  1936). -  Noujdin,  L i n d s l e y _et a l .  1933a;  (i960)  X - r a y i n d u c e d a l a r g e number o f  s e x - l i n k e d r e c e s s i v e m u t a n t s t h a t were v i a b l e a s X / Y m a l e s but  l e t h a l as X/0 i n d i v i d u a l s .  bobbed l e t h a l s ,  Excluding  the induction of  a l l o f t h e s e m u t a n t s were a s s o c i a t e d  euchromatic-heterochromatic rearrangements, thus one  of the c r i t e r i a for position effect.  with  fulfilling  Lindsley  suggests  t h a t these mutants a r e v a r i e g a t i n g f o r l e t h a l mutations a l t h o u g h no s o m a t i c p h e n o t y p e i s v i s i b l e . More r e c e n t  studies  shown s i g n i f i c a n t correlated with  o f v a r i e g a t i n g gene p r o d u c t s h a v e  increases  increases  w i t h i n a s e x (Bahn,  1971;  i n v a r i e g a t i n g enzyme  activity  i n t h e number o f Y - c h r o m o s o m e Gerazimova e t a l . ,  1972).  I n many  v a r i e g a t i n g s y s t e m s , t h e m o s a i c i s m i s so e x t r e m e t h a t  normal  t i s s u e c a n be o b s e r v e d o n l y when e x t r a Y - c h r o m o s o m a l  material  i s present  (Gersh,  I963)•  This  t a i n mutants t h a t c a n s u r v i v e s o r y Y-chrdmosomes ( K e r s c h n e r , Ben  Zeev and F a l k ,  jority  1966).  i s w e l l i l l u s t r a t e d by cer-  only  19^+9;  L i n d s l e y _et a l . ,  i960;  T h u s , i t a p p e a r s f o r t h e v a s t ma-  o f v a r i e g a t i n g systems t h a t  Y-chromosomal m a t e r i a l  i n the presence o f acces-  the effect ofadditional'  i s a potent suppression  o f t h e mutant  phenotype. T e m p e r a t u r e i s a l s o known t o be a m o d i f i e r e f f e c t v a r i e g a t i o n i n somatic t i s s u e .  ofposition-  I n general,  mosaic  8.  stocks r a i s e d a t lower temperatures e x h i b i t a l a r g e r proport i o n o f mutant t i s s u e t h a n those r a i s e d a t h i g h e r t e m p e r a t u r e s . Thus, t h e t y p i c a l phenotypic response t o l o w temperature i s i n c r e a s e d mutant e x p r e s s i o n .  The p h e n o t y p e  wards w i l d type as temperature ability  o f temperature  i smodifiedt o -  i s increased.  The m o d i f y i n g  i s a phenomenon t h a t h a s b e e n  extensively  s t u d i e d f o r many v a r i e g a t i n g m u t a n t s (Gowan a n d Gay, 193^» K a u f m a n n , 19^2; S t e r n a n d K o d a n i , 1955; S c h a l e t , 1 9 6 9 ) . e f f e c t has a l s o been extended 1971)  t o t h e enzymatic l e v e l  and most o f t h e v a r i e g a t i n g l e t h a l systems  (Bahn,  (Ben Zeev  1966).  and F a l k , The  This  e x p l a n a t i o n o f the temperature  e f f e c t has been ap-  p r o a c h e d b y many a u t h o r s ( P r o k o f y e v a - B e l g o v s k y a , 19^5; S t e r n and K o d a n i , 1955)> a n d a common d e d u c t i o n i s made b y a l l . They suggest t h a t l a r g e r a r e a s o f g e n e t i c m a t e r i a l a r e s u b j e c t to  i n a c t i v a t i o n a t lower temperatures.  This i s strongly  sup-  p o r t e d by experiments i n v o l v i n g mutants t h a t v a r i e g a t e f o r numerous l o c i . phenotypes  A t lower temperatures, t h es e v e r i t y o f the  increases i n relation to their proximity to the  heterochromatic breakpoint. variegating loci  A l s o , a t reduced  temperatures,  c a n be i d e n t i f i e d t h a t h a v e p r e v i o u s l y e x -  h i b i t e d a w i l d phenotype. t h a t the temperature  These e x p e r i m e n t s s t r o n g l y  suggest  e f f e c t i n v o l v e s a mutant g r a d a t i o n de-  p e n d e n t u p o n t h e p r o x i m i t y o f t h e w i l d t y p e gene t o t h e b r e a k p o i n t o f the rearrangement. One w o u l d n o t e x p e c t t e m p e r a t u r e t o be a s c o n s i s t e n t a s  9.  o t h e r m o d i f i e r s o f v a r i e g a t i o n - a s many m u t a n t s  derive  phenotype  protein  from thermal i n s t a b i l i t y  o f abnormal  S h o u l d a m u t a n t enzyme be h e a t l a b i l e , mutant e x p r e s s i o n a t t h e r e s t r i c t i v e  their forms.  one w o u l d  e x p e c t a more  temperature.  T h i s type  o f e x p r e s s i o n has been observed f o r t h e mutant l i g h t  ( I t ) and  f o r b r i s t l e number i n I n ( l ) s c u t e - 4 ( G e r s h , 19^9; M a m p e l l , 1956b).  A s v a r i e g a t i o n i s a phenomenon a s s o c i a t e d w i t h  proximity  to a euchromatic-heterochromatic junction,  one e x p e c t s  adjacent'.to t h e b r e a k p o i n t s t o v a r i e g a t e .  However, owing t o  t h e chromosomal breakage  and r e a r r a n g e m e n t ,  the normal  loci  inter-  g e n i c r e l a t i o n s h i p may be r a d i c a l l y a l t e r e d a n d t h e r e s u l t i n g phenotype  may r e a c t u n c o n v e n t i o n a l l y t o t e m p e r a t u r e  T h i s i s e x e m p l i f i e d by t h e complex i m p a i r e d by t h e s c u t e - 8 i n v e r s i o n . i n a phenotype wing  (Hw).  result  mosaic  l o c u s s c u t e (_sc) , w h i c h i s T h i s rearrangement  f o r s c u t e (_sc) , a c h a e t e  results  (ac) and H a i r y  The v a r i e g a t i o n o f t h e s c u t e a n d a c h a e t e  locus  i n a r e d u c t i o n o f b r i s t l e number a t l o w e r t e m p e r a t u r e s .  The m u t a n t f o r m o f Hw,  however, r e s u l t s i n a c c e s s o r y b r i s t l e s  a t l o w e r t e m p e r a t u r e s ( C r e w a n d Lamy, 19^0; It  changes.  i s o b v i o u s t h a t t h e compound e f f e c t  g e n e s may p r o d u c e expected form. of variegated  a phenotype  Temperature  differing  Sutton,.1943b).  o f numerous v a r i e g a t i n g s i g n i f i c a n t l y from t h e  a p p e a r s t o be a n i m p o r t a n t m o d i f i e r  e x p r e s s i o n b u t one m u s t e x e r c i s e c a u t i o n when  i n t e r p r e t i n g d a t a d e r i v e d from complex The t e m p e r a t u r e  mosaic  systems.  s e n s i t i v e p e r i o d has been s t u d i e d f o r a  10.  number o f v a r i e g a t i n g m u t a n t s . a s s o c i a t e d w i t h the  scute-8,  The  the  mosaic b r i s t l e  s c u t e - ^ and  v e r s i o n s i s s e n s i t i v e to temperature i n s t a r l a r v a e and  two  Lamy, 19^-0; S u t t o n ,  days a f t e r puparium f o r m a t i o n  19^3b; G e r s h ,  ture  S c h u l t z , 1956;  scute-Sl i n -  changes between l a t e  19^9)-  The  s i m i l a r to t h a t seen w i t h the w h i t e - m o t t l e d 19^8;  the  Hartmann-Goidstein,  t h e a f f e c t e d l o c u s w o u l d be  expected  c i a t e d w i t h t h i s phenomenon a r e l a c k i n g and to e x p l a i n the developmental  sition-effect variegation.  Future  (Crew  mutants  1967)•  t o be  third and  observation i s (Chen,  The  s e n s i t i v e p e r i o d appears to precede the time  failed  phenotype  at  active. these  or molecular  temperawhich Data  asso-  s t u d i e s have b a s i s of  i n v e s t i g a t i o n s must  po-  vary  the research s t r a t e g i e s to provide f u r t h e r valuable  informa-  t i o n concerning  through  the r e g u l a t i o n o f v a r i e g a t i n g genes  development. The  most p r o f o u n d  heterochromatin effect  content.  The  most o b v i o u s  melanogaster,  localize  specific  i s genomic  example o f  i s the v a r i e g a t i o n - s u p p r e s s i n g a c t i v i t y  Y-chromosome w h i c h h a s D.  m o d i f i e r of p o s i t i o n e f f e c t  this  of  the  been d i s c u s s e d p r e v i o u s l y .  In  many e x p e r i m e n t s  have been u n d e r t a k e n  to  r e g i o n s o f t h e Y-chromosome w h i c h m e d i a t e  the mosaic  suppression  R e i n , 1962;  Brosseau,  (Baker 196^).  and  S p o f f o r d , 1959;  Baker  T h e s e s t u d i e s h a v e b e e n hampered  by problems i n v o l v e d w i t h d e f i n i n g h e t e r o c h r o m a t i c t h e Y-chromosome h a s  and  only the f e r t i l i t y  c l e o l u s o r g a n i z e r as r e f e r e n c e p o i n t s .  f a c t o r s and The  authors  content the  as  nu-  concluded  t h a t the  ability  suppression R'  could not  be  correlated with i t s size.  h y d e i > H e s s ( 1 9 7 0 ) r e p o r t s t h a t two  sing regions A similar and  of a Y-chromosomal fragment to mediate mosaic  s i t u a t i o n has  Spofford, The  e x i s t at very  specific  s i t e s on t h e  b e e n i m p l i e d f o r D.  results.  i n f l u e n c e the  data  the  and  ex-  this  therefore I  characteristic  shall  features  Y-chromosome.  O r i g i n a l l y , Bridges some was  responsible  I n h i s s t u d i e s on discovered male, but  f o r male f e r t i l i t y  sex  although  t h a t the  i n D.  and  X/Y  f o r m e r c l a s s was  flies  sterility  sterile.  Safir  s h o r t arm  o b s e r v e d i n X/0  (K ) and  the  sperm,  L a t e r work r e -  f a c t o r s present  l o n g arm  the  males i s a r e s u l t  (K-, ) o f t h e  S  mosome ( B r o s s e a u ,  ( 1 9 2 0 ) was  m a l e s do n o t p r o d u c e m o t i l e  o f a d e f i c i e n c y of a group of f e r t i l i t y both the  Bridges  were p h e n o t y p i c a l l y  t h e i r g e n i t a l i a a p p e a r t o be n o r m a l .  v e a l e d .that the  Y-chromo-  melanogaster.  chromosome n o n - d i s j u n c t i o n ,  t h a t b o t h X/0 the  (1913) d i s c o v e r e d  t o e s t a b l i s h t h a t X/0  on  Y-chro-  -L  1960b).  I n a d d i t i o n to the f e r t i l i t y  f a c t o r s , the  b e e n shown t o c a r r y a b o b b e d l o c u s the  (Baker  thesis  There are.numerous p r o p e r t i e s of  d i g r e s s a t ..this p o i n t t o r e v i e w  is  melanogaster  a f a c t o r that g r e a t l y i n f l u e n c e s the  chromosome w h i c h may  has  Y-chromosome.  Y-chromosome i s o f s p e c i a l i n t e r e s t t o t h i s  perimental  first  v a r i e g a t i o n suppres-  1959)•  a s i t a p p e a r s t o be  of the  In  Y-chromosome  ( S t e r n , 1927),  s i t e o f t h e rRNA g e n e s ( R i t o s s a and  Spiegelman,  that 1965).  The b o b b e d s i t e h a s b e e n i d e n t i f i e d  on t h e s h o r t arm o f t h e  Y-chromosome a n d i s h o m o l o g o u s t o t h e b o b b e d l o c u s s i t u a t e d i n the proximal  heterochromatin  o f t h e X-chromosome.  I t has  a l s o been d e t e r m i n e d t h a t t h e bobbed phenotype ( d e l a y e d opment,  s h o r t , t h i n b r i s t l e s and a b d o m i n a l e t c h i n g )  by a r e d u c t i o n i n t h e numbers o r Y bobbed l o c u s  the  The b o b b e d  locus  c y t o l o g i c a l l y and b i o c h e m i c a l l y as  s i t e of the nucleolus organizer region  S p i e g e l m a n , 1965; P e r r y ,  i s caused  o f rRNA g e n e s a t e i t h e r t h e X  ( R i t o s s a e_t a l . , 1966) .  has a l s o been i d e n t i f i e d  devel-  1967).  ( R i t o s s a and  Owing t o t h e r e d u n d a n c y a t  t h e Y bobbed l o c u s and i t s s i m i l a r i t y t o t h e homologous X-chromosome s i t e ,  t h e Y bobbed l o c u s m u t a n t s have been ex-  t e n s i v e l y s t u d i e d and t h i s has p r o v i d e d t a i n i n g t o t h e r e g u l a t i o n o f rRNA Initially,  and  regions  stained darkly  appeared condensed throughout the m a j o r i t y o f m i t o s i s These a r e a s were termed h e t e r o c h r o m a t i c  s o o n i t was d e m o n s t r a t e d t h a t t h e s e  fied  regions  were d i s t i n g u i s h e d b y t h e i r s t a i n i n g  I t was a p p a r e n t t h a t t h e s e  ( H e i t z , 1933)*  the  per-  synthesis i n Drosophila.  t h e Y-chromosome a n d t h e c e n t r o m e r i c  o f t h e o t h e r chromosomes properties.  much i n f o r m a t i o n  so-called "genetically inert"  regions  corresponded to  regions previously  i n D. m e l a n o g a s t e r chromosomes  and  identi-  ( M u l l e r and P a i n t e r , 1932).  E v i d e n c e q u i c k l y mounted t o s u g g e s t t h a t t h e p r o p e r t i e s of heterochromatin euchromatin.  were much d i f f e r e n t t h a n t h o s e  of the  I n e a r l y s t u d i e s , t h e Y-chromosome w a s . u s e d e x -  t e n s i v e l y t o m o d i f y genomic h e t e r o c h r o m a t i n  content.  These  works i d e n t i f i e d  a host o f p r o p e r t i e s  chromatic content: modification  19^7;  (Darlington, and  Gay, 1933;  Grell,  Hannah,  Schultz,  1959)>  of specific  1951)>  1939;  a t t r i b u t a b l e to heterogene  variegation  action  control  B a k e r and S p o f f o r d ,  (Gowan  1959;  and s u p p r e s s i o n o f l e t h a l m u t a t i o n s  (Lindsley  et a l . , I 9 6 0 ) . A l t h o u g h most s t u d i e s  on h e t e r o c h r o m a t i c c o n t e n t  Y-chromosome m o d i f i c a t i o n s , features basal  associated  with  there  a r e many e x a m p l e s o f s i m i l a r  other heterochromatic regions.  ported that  Noujdin  of yellow  (v;) , a n d l a t e r  scute-8 i n d i v i d u a l s c a r r y i n g  small  19^*0  •  1938;  a full  1959).  X-hetero-  variegation I t i s also  evident  T h i s i s apparent viewing the  i n v o l v i n g comparisons o f v a r i e g a t i o n  centromeric regions  variegation  f o r these  complement o f X - h e t e r o c h r o m a t i n h a s a s i m i l a r e f -  m a l e s a n d X/Y m a l e s ( G r e l l , The  t o enhance  Baker and S p o f f o r d ,  f e c t a s a s i n g l e Y-chromosome. many s t u d i e s  individuals  Deficiencies of the basal  c h r o m a t i n have a l s o been r e p o r t e d  that  X-heterochromatic  l a c k i n g t h e d u p l i c a t i o n commonly w e r e v a r i e g a t e d genes (Noujdin,  re-  sup-  determined  d u p l i c a t i o n s w e r e r a r e l y m o s a i c f o r y_ o r a c w h i l e  (Panshin,  (1938)  addition of X-heterochromatin successfully  pressed variegation  that  The  h e t e r o c h r o m a t i n o f t h e X-chromosome a l s o h a s b e e n shown  t o be a p o t e n t s u p p r e s s o r o f v a r i e g a t i o n .  In(l)  involve  1958;  Bahn,  1971).  o f t h e autosomes a l s o  suppressing function.  t h i s a r e a i n v o l v e s D f ( 2 R ) M-S2  i n X/X f e -  exhibit a  The b u l k o f t h e w o r k i n  10 w h i c h i s a l a r g e d e l e t i o n o f  lk.  c e n t r o m e r i c h e t e r o c h r o m a t i n on Holm, 1 9 7 5 ) .  ( H i l l i k e r and  the  o f chromosome 2  r i g h t arm  Schultz(1939)  observed that  the  p r e s e n c e of t h i s d e f i c i e n c y g r e a t l y enhanced v a r i e g a t i o n the  white  (w) , y e l l o w  cent studies  (y_) and  b r o w n (bw)  mutants.  for  More r e -  i n v o l v i n g o t h e r m o s a i c systems have  corroborated  t h i s phenomenon ( B r o s s e a u , I960; L i n d s l e y _et a l . , i960) . Numerous e x p e r i m e n t s now ing  of the  exist suggesting that  fundamental b a s i s  an  understand-  of heterochromatization  will  u l t i m a t e l y l e a d t o a c o m p r e h e n s i o n o f t h e phenomenon o f tion-effect The  variegation.  a s s o c i a t i o n b e t w e e n p o s i t i o n e f f e c t and  matization  i s s t r o n g l y i m p l i e d by  The  great  majority  the  rearrangement of the  matin within  of the  the  genetic  genome h a s  observations. found to  Also,  the  following i s a  c y t o l o g i c a l l y as  staining, Feulgen p o s i t i v e material  that remains  throughout the m a j o r i t y  cycle  of the  i s contrasted  cytologically visible a t metaphase. c h r o m a t i n and  The  expres-  synopsis reference  to p o s i t i o n e f f e c t .  Heterochromatin i s defined  region  heterochro-  a p r o f o u n d e f f e c t on t h e The  involve  proximity  amount o f  of heterochromatin with p a r t i c u l a r  to those f a c e t s relevant  This  heterochro-  e u c h r o m a t i c gene i n t o t h e  variegating locus.  subject  two  of v a r i e g a t i n g mutants are  o f a h e t e r o c h r o m a t i c segment.  s i o n of the  posi-  with  cell  densely visible  (Heitz,  1933)-  e u c h r o m a t i n w h i c h becomes  i n l a t e p r o p h a s e and  d i s t i n c t i o n of the  e u c h r o m a t i n on t h e  only  stains well  elements of  hetero-  b a s i s of c y t o l o g i c a l e v i -  15-  dence does n o t s e r v e t o a d e q u a t e l y d e f i n e t h e s e genetically.  The  variability  development suggests  elements  of regional s t a i n i n g  throughout  s t r o n g l y t h a t the c y t o l o g i c a l  definition  w i l l not c o r r e l a t e d i r e c t l y w i t h the g e n e t i c d e f i n i t i o n . This point i s well i l l u s t r a t e d heterochromatin v a r i a t i o n .  i n the d i s c u s s i o n  I n mammalian f e m a l e s , t h e  o f L y o n i z a t i o n i n v o l v e s t h e random i n a c t i v a t i o n o f a X-chromosome t h r o u g h o u t system  of  the somatic t i s s u e  a c h i e v e s dosage compensation  process single  ( L y o n , 1962).  f o r females  as h a l f  of  t h e i r c e l l s h a v e one X-chromosome i n a c t i v a t e d w h i l e t h e h a l f have the homologous X i n e r t . menon i s r e c o g n i z e d by t h e p r e s e n c e  somatic  X euchromatin  cells.  The  i n t o an i n e r t  o f h i g h l y condensed  s t r u c t u r e i s termed  h e t e r o c h r o m a t i z a t i o n and t h i s phenomenon  X-chro-  are p e c u l i a r  h e t e r o c h r o m a t i z a t i o n of the  to  entire  facultative  characteristically  i n v o l v e s the i n a c t i v a t i o n of n o r m a l l y a c t i v e chromatin. u l t a t i v e h e t e r o c h r o m a t i n c a n be c o n t r a s t e d w i t h h e t e r o c h r o m a t i n w h i c h makes up  other  C y t o l o g i c a l l y , t h i s pheno-  mosomal m a t e r i a l known a s B a r r b o d i e s w h i c h female  This  the remainder  Fac-  constitutive  of the  condensed  chromatin.. C o n s t i t u t i v e h e t e r o c h r o m a t i n i s t h a t e l e m e n t commonly observed  i n t h e c e n t r o m e r i c r e g i o n s , a t chromosome t i p s o r i n  the v i c i n i t y  of the n u c l e o l u s organizer r e g i o n .  There  also i s o l a t e d regions of i n e r t chromatin dispersed the euchromatin  which are termed i n t e r c a l a r y  are  throughout  heterochromatin.  C o n s t i t u t i v e heterochromatin i s the m a t e r i a l c u s t o m a r i l y asso-  16.  dated  with position-effect  variegation.  In Drosophila melanogaster,  the genomic c o n t e n t o f h e t 25% ( P e a c o c k  e r o c h r o m a t i n h a s b e e n e s t i m a t e d t o be 1973).  The  m a j o r i t y of t h i s m a t e r i a l i s found  Y-chromosomes b u t t h e r e a r e autosomes as w e l l .  on t h e X  s i g n i f i c a n t p o r t i o n s found  Euchromatic  r e g i o n s has been observed  et a l . ,  on  i n t e r c h a n g e s w i t h any  to e l i c i t  or the  of  these  v a r i e g a t e d gene e x p r e s s i o n .  Much e f f o r t has b e e n a p p l i e d t o t h e d i s t i n c t i o n o f h e t erochromatin from  euchromatin.  T h e r e .are c y t o l o g i c a l t e c h -  niques that s t a i n these•regions d i f f e r e n t i a l l y ing technique i s s p e c i f i c S e v e r a l authors suggest sition  for constitutive  t h a t t h e DNA  and  the  heterochromatin.  a s s o c i a t e d p r o t e i n compo-  i n heterochromatin i s fundamentally d i f f e r e n t  t h a t observed B r u t l a g , 1979;  ( B e r l o w i t z , 1965;  i n euchromatin Blumenfeld,  1979).  C-band-  The  DNA  than  Hsien.and  constitution  of  h e t e r o c h r o m a t i c r e g i o n s h a s b e e n s t u d i e d t h o r o u g h l y and p e a r s t o be c o m p o s e d p r i m a r i l y o f r e p e t i t i v e ( Y a s m i n e h and Y u n i s , 1969; e t a l . 1 1972;  Blumenfeld  Peacock et a l . ,  1973).  d i f f e r e n c e s should produce i n s i g h t chromosome c o n d e n s a t i o n and The  most p r o f o u n d  gene  1971;  s t u d i e s of  satellite  sequences.  constitutive heterochromatin.  these  euchro-  t o be t h e e x i s t e n c e o f  T h i s t y p e o f DNA  s e q u e n c e s and  Kram  the mechanisms o f  b i o c h e m i c a l d i f f e r e n c e between  heterochromatin appears  in  into  DNA  regulation.  m a t i n and  highly repetitive  satellite  and F o r r e s t , The  ap-  i s composed o f s h o r t ,  are found I n D.  the  almost  exclusively  melanogaster,  Peacock  17-  e t a l . (1973) h a v e i d e n t i f i e d f o u r m a j o r s a t e l l i t e t h a t make up  the vast m a j o r i t y  sequences  of the h i g h l y r e p e t i t i v e  These a u t h o r s a l s o l o c a l i z e d the  d i s t r i b u t i o n of the  satellite  s e q u e n c e s by h y b r i d i z i n g l a b e l l e d cDNA t o d e n a t u r e d chromosomes o r m i t o t i c p r e p a r a t i o n s  central region  i n the polytene  heterochromatic s i t e s are  i n the  chromosomes w h i l e  defined  polytene  from b r a i n c e l l s .  a l l y a l l o f t h e s e sequences were i d e n t i f i e d  by  DNA.  Virtu-  chromo-  very  specific  t h e m i t o t i c chromosomes  ( P e r r a u l t et a l . , 1978). T h e r e i s good e v i d e n c e t h a t sequences have a h i g h l y s p e c i f i c  each of the major  satellite  d i s t r i b u t i o n i n the  genome.  P e r r a u l t e t a l . (1978) f o u n d d i f f e r e n c e s b e t w e e n X/Y t e m p l a t e DNA  and  e_t a l . (1975)  Goldring  sequence i s s i t e - s p e c i f i c . mate t h a t 80fo o f t h e major sequences.  and  suggest t h a t  Peacock e t - a l .  X/X  each  (1973) a l s o  esti-  h e t e r o c h r o m a t i n i s composed o f t h e  This  observation  has  involved with d e f i n i n g possible coding  four  promoted i n v e s t i g a t i o n s regions  within  the  heterochromatin. The  genetic  questioned.  i n e r t n e s s o f h e t e r o c h r o m a t i n has  I n r e p o r t i n g the  structed, Sturtevant way  factors."  actual relative He  l i n k a g e map  (1913) r e m a r k e d t h a t  of knowing whether or not  sent the  first  a t one  end  of the  i s no  as drawn  apart  of  o b s e r v e d i n h i s work t h a t t h e X - l i r i k e d  were crowded t o g e t h e r  been  ever con-  "...there  these distances  spacial distances  long  chromosome.  repre-  these genes The  X-ray i n d u c t i o n of i n v e r s i o n s with heterochromatic breaks  was  18.  f o u n d t o t r a n s f e r l a r g e b l o c k s o f c h r o m a t i n i n t o new e n v i r o n m e n t s ( M u l l e r a n d P a i n t e r , 1929)• little  Recombination  d a t a show t h a t  exchange o c c u r s i n t h e c e n t r o m e r i c r e g i o n o r h e t e r o c h r o -  m a t i c r e g i o n s t h a t have been t r a n s f e r r e d (Offerman  e t a l . , 1931)'  into the  euchromatin  The i n d u c t i o n o f m u t a n t s m a p p i n g i n  the heterochromatic r e g i o n s has proven  t o be v e r y  difficult.  A number o f g e n e s h a v e b e e n a s s o c i a t e d w i t h h e t e r o c h r o m a t i c regions but these serve t o i n d i c a t e the lowgenetic d e n s i t y in  such a r e a s .  Data  such a s these s t r o n g l y support t h e n o t i o n  of  genetic inertness of heterochromatic regions. Fine s t r u c t u r a l analysis o f the basal heterochromatin o f  t h e X-chromosome s u g g e s t s t h a t t h e t r a n s i t i o n f r o m to  heterochromatin i s gradual r a t h e r than abrupt  1978).  Numerous c o m p l e m e n t a t i o n  euchromatin (Lifschytz,  g r o u p s c a n be i d e n t i f i e d  w i t h i n t h e t r a n s i t i o n zone a n d i t i s b e l i e v e d t h a t t h e s e s i t e s are separated by i n t e r c a l a r y heterochromatin.  coding  I n the  a r e a p r o x i m a l t o t h e bobbed l o c u s , t h e r e a r e o n l y l o n g h e t e r o chromatic gions.  sequences a p p a r e n t l y u n i n t e r r u p t e d by coding r e -  O t h e r a u t h o r s have s u g g e s t e d  that the cytological  o b s e r v a t i o n o f " d i f f u s e " h e t e r o c h r o m a t i n i n p o l y t e n e chromosomes r e p r e s e n t s a v i s u a l i z a t i o n o f t h e t r a n s i t i o n a l r e g i o n between t r u e euchromatin L a k h o t i a and Jacob,  and t r u e heterochromatin  197*0.  (Gall,  A t t h i s time, the d i f f u s e  1973;  hetero-  c h r o m a t i n was t e r m e d B w h i l e t h e more c o n d e n s e d f o r m was t e r m e d A.  A v a r i e t y o f experiments  have s i n c e enhanced  this  a s s o c i a t i o n a n d i t seems l i k e l y t h a t t h e B h e t e r o c h r o m a t i n  a c t u a l l y r e p r e s e n t s the t r a n s i t i o n The almost  zone.  p r o x i m a l h e t e r o c h r o m a t i n o f the major autosomes are  e n t i r e l y v o i d of mutable l o c i .  p o u n d a u t o s o m e s and  subsequent  l o c a t i o n o f the genes l i g h t  The  d e t a c h m e n t o f com-  a n a l y s i s has  confirmed  ( i t ) and r o l l e d  the  ( r l ) i n the  i m a l h e t e r o c h r o m a t i n o f chromosome 2 ( H i l l i k e r  prox-  and H o l m , 1975)'  F u r t h e r s t u d i e s o f chromosome 2 h e t e r o c h r o m a t i n i n v o l v e d t h e i n d u c t i o n of p o i n t mutations w i t h i n heterochromatin u s i n g the m u t a g e n e t h y l methane s u l f o n a t e (EMS). identified  Numerous l o c i  on e i t h e r s i d e o f t h e c e n t r o m e r e  d e n s i t y was  still  but the g e n e t i c  e s t i m a t e d t o be l e s s t h a n 1%  ved i n euchromatin  (Hilliker,  1976).  were  of t h a t obser-  A number o f c o m p l e m e n t -  a t i o n g r o u p s have been r e c o v e r e d from t h e c e n t r o m e r i c r e g i o n s of  chromosome  assignment some l o c i  but u n f o r t u n a t e l y t h e i r  i s speculative  ( B a l d w i n and  heterochromatic  S u z u k i , 1971)-  Although  a p p e a r t o be p r e s e n t i n t h e l a r g e b l o c k s o f a u t o -  s o m a l h e t e r o c h r o m a t i n , i t seems t h a t t h e m a j o r i t y o f t h i s m a t i n i s i n e r t and The  serves a non-coding  function.  e x i s t e n c e o f s p e c i f i c X-chromosome l o c i w i t h i n h e t e r o -  c h r o m a t i n has been i m p l i c a t e d  i n s t u d i e s i n v o l v e d w i t h the  h e t e r o c h r o m a t i c i n f l u e n c e on c e r t a i n a u t o s o m a l (197^) r e p o r t s t h a t t h e m a t e r n a l oocyte  chro-  (abo)  the presence fragments.  loci.  e f f e c t mutants,  Sandler  abnormal  and d a u g h t e r l e s s ( d a ) , a r e p a r t i a l l y r e v e r t e d i n of e x t r a copies of p a r t i c u l a r X He  s u g g e s t s t h a t t h e s e l o c i may  t h e s i s o f a h e t e r o c h r o m a t i c gene p r o d u c t  heterochromatic r e g u l a t e the  ( P a r r y and  syn-  Sandler,  20.  1975)•  Recently,  (1977) h a s  Sandler  o u t l i n e d a group  of  t i g h t l y l i n k e d autosomal markers t h a t i n t e r a c t w i t h the heterochromatin. between these area  He  regions  of proximal Procunier  w i t h i n the  a l l u d e s t o a more g e n e r a l  X  and  as t h e m u t a n t s a r e  (1978) r e p o r t  same r e g i o n may  regions may  The  tenance of t h e i r t o 80%  repeats  structure.  o f 600  "inert  certain  regions" undefined.  of  The  satellite and  are  of a f i v e  to twelve  compaction of the  and,  main-  s e q u e n c e s compose  a r r a n g e d i n homoge-  I t seems l i k e l y  region into  t h a t the  proces-  condensed b l o c k s  c h r o m a t i n i n t o an  a t t h e moment, t h e  tan-  b a s e p a i r u n i t ( P e a c o c k _et a l . ,  specific  h i s t o n e components appears t o mediate the  invol-  inactive state.  Numerous t h e o r i e s h a v e b e e n a d v a n c e d a s t o t h e n a t u r e process  and  the  k i l o b a s e s , r e p r e s e n t i n g thousands of  Endow e t a l . , 1 9 7 5 ) -  the  rDNA  the mechanisms i n v o l v e d i n the  sing of t h i s d i s t i n c t i v e ves  compen-  and  must i n v o l v e t h e p e c u l i a r c h e m i s t r y  of the heterochromatin  neous b l o c k s  1973;  compensa-  a s s o c i a t i o n between p o s i t i o n - e f f e c t v a r i e g a t i o n  c o m p a c t e d c h r o m a t i n and  dem  suggest t h a t the  the  of the  r e g u l a t o r y f u n c t i o n s w h i c h , as y e t , are  heterochromatin  up  The  i n t e r a c t i o n between s p e c i f i c l o c i  locus  of  to c o n t r o l the  individual i s deficient  of heterochromatin  serve  evidence that a  organizer region.  ( c r ) , i s reported  s a t i o n o f rRNA when an -The  s e n s i t i v e to a l a r g e  c o n t r o l the m u l t i p l i c i t y  rRNA g e n e s i n t h e n u c l e o l u s  cistrons.  interaction  heterochromatin. Tartof  t o r y response locus  X  binding of  of  this  modified  compaction of  chro-  21 .  matin (Blumenfeld  jet a l . , 1 9 7 8 ) .  t e i n s a r e " b e l i e v e d a l s o t o be of i n a c t i v e chromatin The  Numerous n o n - h i s t o n e  i n v o l v e d w i t h the  i n g p r o t e i n s may  determination  s t r u c t u r e d u r i n g development  r e g i o n a l c o m p a c t i o n o f DNA provide  m e d i a t e d by  pro-  ( P a u l , 1970)-  specific  a t e s t a b l e e x p l a n a t i o n o f t h e mech-  anism of p o s i t i o n e f f e c t .  I t has  been p r e v i o u s l y observed  t h a t the d e r i v a t i o n of a v a r i e g a t e d phenotype i n v o l v e d i n a c t i v a t i o n o f e u c h r o m a t i c genes i n t r o d u c e d of heterochromatin.  Spofford  g a t i n g gene a p p e a r s t o be  i n a c t i v a t e d by  Zuckerkandl  (197*0 h a s  f e c t may  e x p l a i n e d by a l o c a l i z e d  by  i n t o the  the proximity  (1976) comments t h a t t h e  a s s o c i a t e d - w i t h i t s p r o x i m i t y to the  be  bind-  a "spreading  effect"  heterochromatin.  a l s o suggested t h a t the  spreading  ef-  i n a c t i v a t i o n of the  d i f f u s i o n of a substance n a t i v e to the  S p e c i f i c histones or non-histone  varie-  condensed  p r o t e i n s may  gene  chromatin.  represent  this  f a c t o r as e u c h r o m a t i c genes t r a n s f e r r e d i n t o the v i c i n i t y heterochromatin  may  be  i n f l u e n c e d by t h e D N A - b i n d i n g p r o t e i n s  that act to i n a c t i v a t e chromatin. hypothesis the  Evidence supporting  i s r e p o r t e d by M o o r e e t a l . , (1979) who  e f f e c t o f h i s t o n e gene d e f i c i e n c i e s on t h e  v a r i e g a t i n g genes.  These a u t h o r s  mosaicism i n v a r i e g a t i n g mutants. and  provide  explored  extent  The.data support  condensation  developmental stage  at which  or  of  reduction of  their  f u r t h e r e v i d e n c e t h a t h i s t o n e s may  the v e h i c l e of chromatin The  this  expression  predicted that a  o f c e l l u l a r amounts o f h i s t o n e w o u l d r e d u c e t h e  hypothesis  of  be  heterochromatization.  heterochromatization  22.  o c c u r s i s o f i n t e r e s t a s t h i s may d e t e r m i n e locus to variegate.  Chromatin  able a t the blastoderm  stage  the a b i l i t y  condensation i s f i r s t  i a t i o n have n o t been i n i t i a t e d  ( I l l m e n s e e , 1973).  p a r e n t t h a t most g e n e s i n i t i a t e  differentI+- i s a p -  As t h e f i r s t  heterochroma-  s t a g e , most g e n e s w o u l d be  ject to heterochromatin-induced  icism,  1968).  t h e i r function after the blas-  toderm stage has been completed.  In  detect-  ( H u e t t n e r , 1933; M a h o w a l d ,  P r i o r t o t h i s p e r i o d , gene a c t i v i t y a n d chromosome  tization coincides with this  of a  sub-  variegation.  r e v i e w i n g t h e many e x a m p l e s o f p o s i t i o n e f f e c t mosai t i s apparent  t h a t t h e e x t e n t o f mutant t i s s u e i s  d i f f e r e n t f o rseparate mutations. t i s s u e appears  I n many c a s e s , t h e m u t a n t  a s l a r g e , homogeneous c l o n e s o f c e l l s w h i l e  a n o t h e r m u t a n t may p r e s e n t a v e r y f i n e - g r a i n e d  mosaicism.  This difference i s attributed to the timing of the o r i g i n a l i n a c t i v a t i o n event.  A n e a r l y d e c i s i o n a l l o w s numerous  tic  d i v i s i o n s and s u b s e q u e n t l y , a l a r g e c l o n e o f mutant  sue  i s formed.  and  t h e s e a r e seen as " s a l t and pepper"  Late decisions r e s u l t  From t w i n s p o t e x p e r i m e n t s  tis-  i n much s m a l l e r c l o n e s mosaicism.  involving mitotic  t i o n , many a u t h o r s h a v e a t t e m p t e d  mito-  recombina-  t o e s t i m a t e t h e number o f  p r o g e n i t o r c e l l s present a t v a r i o u s developmental  stages.  F o r t h e mesonotum, t h e r e seems t o be l e s s t h a n 10 p r o g e n i t o r c e l l s i n newly hatched  l a r v a e a n d t h i s e s t i m a t e i s a l s o ob-  served a t the blastoderm n u c l e i Merriam,  1969, 1971)-  stage  Experiments  ( G a r c i a - B e l l i d o and  such as these suggest  that  23-  the d e t e r m i n a t i o n pathways are f i x e d the blastoderm  stage  s o c i a t e d w i t h any  onward and  cell  i n numerous c e l l s  from  t h a t i n a c t i v a t i o n c a n be  division  as-  after.  From t h i s d i s c u s s i o n o f h e t e r o c h r o m a t i n  and  a t i o n w i t h p o s i t i o n - e f f e c t v a r i e g a t i o n , one  can  i t s associsee t h a t  the  complexities involved i n maintaining chromatin s t r u c t u r e throughout  development l i k e l y  i s apparent istic  i n f l u e n c e gene e x p r e s s i o n .  that s p e c i a l i z e d , non-coding f u n c t i o n s character-  of heterochromatin  do n o t p r o v i d e a s u i t a b l e  ment f o r c l a s s i c gene f u n c t i o n .  be v e r y s p e c i a l i z e d i n f u n c t i o n . e v o l v e d two  s i t u a t i o n but they  The  euchromatin  that provide  structurally promoting  separated  and  one  such c o m p a r t m e n t a l i z a t i o n .  would expect  and  r e p r e s e n t s an example o f such t h i s phenomenon h a s One  obvious  Owing t o t h e  structural  selection strict  heterochromatic  a b e r r a n t phenomena t o be  r e o r g a n i z a t i o n of the chromatin.  the  These o p e r a t i o n s have been  t h e r e w o u l d be  c o n s e r v a t i o n of the euchromatic  provides  has  necessary  p r o v i d e s most o f  coding r e g i o n s w h i l e the heterochromatin other non-coding f u n c t i o n s .  may  D r o s o p h i l a melanogaster  separate types of chromatin  cellular functions.  environ-  T h e r e a r e . a number o f g e n e s  t h a t can t o l e r a t e the heterochromatic  and  It  regions,  associated with  the  Position-effect variegation  an a n o m a l y and  consequently,  a t t r a c t e d much a t t e n t i o n r e c e n t l y .  of the important  c o n s i d e r a t i o n s i n t h i s t h e s i s must  be t h e m e c h a n i s m s o f b r i s t l e  development.  The  phenotype t h a t  i s a s s o c i a t e d w i t h the scute i n v e r s i o n s i n v o l v e s the  improper  2k.  expression  o f g e n e s t h a t c o n t r o l t h e d e v e l o p m e n t and  bution of b r i s t l e s lethality  on t h e  epidermal  a s s o c i a t e d w i t h these  r e l a t e d w i t h the b r i s t l e it  s u r f a c e of the f l y .  scute  i n v e r s i o n s may  d e v e l o p m e n t d e f e c t and,  The  be  cor-  therefore,  i s a d v a n t a g e o u s t o e x a m i n e t h e p a t h w a y s by w h i c h t h e  tles  are  of the b r i s t l e formation migrate  development i n v o l v e s the  ognizable  c e l l s a t a b o u t 15  forming  (APF)  (Lees  and  to a s p e c i f i c  nearest  p o i n t on t h e  c o m p l e x a t 25  to the  tormogen l i e s  t o 30  a second c e l l  their  epidermis  socket  linear  tion  nuclei.  puparium  A p a i r of and  The  cell  lying  of the b r i s t l e 1933)-  B e t w e e n 30  and  d i m e n s i o n s by  kO  cells  form a r e c -  and  Beneath  termed the t r i c h o g e n which  gone t h r o u g h n u m e r o u s e n d o m i t o t i c ploid  hours a f t e r  h o u r s APF.  surface forms the  c r e t e s the b r i s t l e m a t e r i a l . enlarge  differentiation  Waddington, 1 9 ^ 2 ) .  i s known a s t h e t o r m o g e n ( W i g g l e s w o r t h ,  cells  bris-  formed.  Normal b r i s t l e  hours,  ten times  and  the sethe have  d i v i s i o n s to produce poly-  A s s o c i a t e d w i t h the p o l y p l o i d y i s the  forma-  of prominent n u c l e o l i which presumably f u n c t i o n to i n -  crease  rRNA p r o d u c t i o n  Initially  (30  b r i s t l e production tormogen begins  later  than the  formation.  the t r i c h o g e n s e c r e t e s a  and  colorless.  bristle  Simultaneous with  i s the development of the b r i s t l e s e c r e t i o n of the  initial  maximum a c t i v i t y  for bristle  hours),  m a t e r i a l which i s s o l i d  The  distri-  socket m a t e r i a l  trichogen activity  a t a b o u t kO  hours.  socket.  The  but b o t h  slightly  reach  t r i c h o g e n and  tor-  25.  mogen a r e a c t i v e l y slightly of  g r o w i n g and s e c r e t i n g m a t e r i a l s  a f t e r 4-0 h o u r s .  After this  time, the large  c y t o p l a s m e s t a b l i s h e d by t h e s e c e l l s  bristle The  complete.  s o c k e t s t r u c t u r e i s c o m p l e t e l y formed i s n o t completed  volume  i s d i m i n i s h e d as the  a n d s o c k e t s t r u c t u r e s become more  while the b r i s t l e  until  a t 48  hours  u n t i l 60 h o u r s . A l l  s e c r e t i o n s f r o m t h e tormogen and t r i c h o g e n have c e a s e d by 70 h o u r s a n d t h e s e c e l l s h a v e now become from t h e o t h e r e p i d e r m a l The  cells.  maturation of the b r i s t l e  a h o l l o w i n g o f t h e immature s o l i d that the hollowing of the b r i s t l e s and c o n t r a c t i o n o f t h e c h i t i n ( L e e s a n d W a d d i n g t o n , 194-2) . 10 h o u r s , t h e b r i s t l e s  indistinguishable  i n v o l v e s p i g m e n t a t i o n and structure.  I t i s suggested  r e s u l t s from t h e hardening  o f which the b r i s t l e  i s made  A f t e r a period of approximately  have a t t a i n e d t h e i r  fully  mature  s t r u c t u r e and a r e p r e p a r e d f o r t h e a d u l t environment. apparent t h a t b r i s t l e of  I ti s  development i n v o l v e s a complex c h a i n  events t h a t i s determined by s t r i c t  genetic controls.  I n v e s t i g a t i o n s o f t h e mutants o f the b r i s t l e  development  pathway p r o v i d e s f u r t h e r i n s i g h t s i n t o t h e mechanisms o f genetic  regulation.  A classic  paper  concerning the d i s s e c t i o n of the b r i s t l e  d e v e l o p m e n t a l p a t h w a y s was w r i t t e n b y L e e s and W a d d i n g t o n  (194-2).  In this  study, the authors investigated a v a r i e t y  o f m u t a n t s t h a t w e r e known t o e f f e c t b r i s t l e determined the developmental  e x p r e s s i o n and  stage a t which the mutation acted.  26.  They d e f i n e d t h e s e d e v e l o p m e n t a l  s t a g e s and  tants:  cell  cell  determination of b r i s t l e  division - split  Dichaete  of c e l l s  (sp_l); a r r i v a l a t epidermal s u r f a c e -  - spineless  (JESS)  trichogen - Stubble  ; chitin  secretion -  singed  ( s n ) , f o r k e d ( f ) ; d a r k e n i n g and h a r d e n i n g - t h e  color"  genes.  The  authors completed  d i f f e r e n t m u t a n t s and  the study w i t h twelve  s u p p o r t i n g the- e x i s t e n c e  a complex pathway c o n t r o l l i n g b r i s t l e d e t e r m i n a t i o n . Of p a r t i c u l a r i n t e r e s t t o t h i s  of  "body  they a l l f i t i n t o these seven c a t e g o r i e s .  T h e i r data provide strong evidence of  mu-  - s c u t e (ssc) ; b r i s t l e  ( D ) ; a r r a n g e m e n t o f t o r m o g e n and  (Sb) j g r o w t h  associated  t h e jsc p h e n o t y p e .  are d e f i c i e n t stage  study i s the  I t has been found  development  t h a t scute mutants  of h a i r c e l l s from the e a r l i e s t p o s s i b l e  ( L e e s and W a d d i n g t o n , 1 9 ^ 2 ) .  pupal  T h i s suggests t h a t the -  i n h e r e n t d e f e c t i n the scute mutants i n v o l v e s the  determina-  t i o n and/or m i g r a t i o n of the b r i s t l e c e l l s .  Further inves-  t i g a t i o n s of the scute developmental  indicate that  profile  t h e t e m p e r a t u r e - e f f e c t i v e p e r i o d o c c u r s a t t h e end larval period.  of the  T h u s , t h e a c t i o n o f t h e w i l d t y p e gene must  o c c u r b e t w e e n t h e end  o f t h e l a r v a l p e r i o d and 1 6 t o 2 0  hours  a f t e r puparium f o r m a t i o n . The was  a s s o c i a t i o n of the b r i s t l e s w i t h the nerve  f i r s t p o i n t e d o u t by S t e r n ( 1 9 3 8 ) .  m a c r o - and m i c r o c h a e t a e  He  observed  network t h a t the  on t h e t h o r a x w e r e i n t i m a t e l y  c i a t e d w i t h a network of p e r i p h e r a l nerve  cells.  asso-  This i s  c o n s i s t e n t w i t h the sensory f u n c t i o n of the b r i s t l e s  and  27.  p o i n t s t o a p o s s i b l e a s s o c i a t i o n "between nervous d i f f e r e n t i a t i o n and t h e s c u t e m u t a t i o n .  C l e v e r (I960) found t h a t  when p e r i p h e r a l n e r v e s were p o i s o n e d by methylene b l u e , t h e tormogen and t r i c h o g e n c e l l s f a i l e d t o d i f f e r e n t i a t e .  It is  p o s s i b l e t h a t t h e f a i l u r e o f nervous growth may i n f l u e n c e the normal g e n e r a t i o n o f t h e b r i s t l e f o r m i n g complex.  Other  d a t a suggest t h a t t h e a c t i o n o f t h e s c u t e - a c h a e t e system i s even e a r l i e r t h a n t h i s s t a g e . C e l l s d e f i c i e n t f o r t h e s c u t e l o c u s can be produced a t d i f f e r e n t t i m e s o f development by i n d u c e d m i t o t i c  exchange.  I t has been observed t h a t t h e s e s c u t e d e f i c i e n t c e l l s a r e a b l e t o d i f f e r e n t i a t e t h e b r i s t l e f o r m i n g complex i f t h e i n d u c t i o n o c c u r s l a t e r t h a n 4-0 t o 4-8 hours (macrochaetae) o r 16 t o 24- hours ( m i c r o c h a e t a e ) b e f o r e puparium f o r m a t i o n ( G a r c i a - B e l l i d o and S a n t a m a r i a , 1978).  There i s some e v i -  dence which s u g g e s t s t h a t t h e mother e p i d e r m a l c e l l  initiates  d i f f e r e n t i a l d i v i s i o n s g i v i n g r i s e t o n e r v o u s and e p i d e r m a l pathways a t t h i s s p e c i f i c t i m e ( G a r c i a - B e l l i d o and M e r r i a m , 1971a; G a r c i a - B e l l i d o and S a n t a m a r i a , 1978). There a r e a number o f mutants w h i c h map t o t h e s c u t e r e g i o n t h a t a r e d e f i n e d as embryonic l e t h a l s .  Histological  d e s c r i p t i o n o f t h e s e mutants r e v e a l e d a b n o r m a l i t i e s i n gast r u l a t i o n w i t h a n o m a l i e s i n s e g r e g a t i o n o f nervous t i s s u e and hypodermis (Ede, 1956b).  Gynandromorph s t u d i e s c a r r i e d  out by G a r c i a - B e l l i d o and S a n t a m a r i a (1978) i n d i c a t e t h a t v i a b l e gynanders o n l y o c c u r when _sc d e f i c i e n c y t i s s u e  does  28.  n o t e x t e n d a c r o s s t h e v e n t r a l m i d l i n e o f t h e embryo f r o m which, presumably,  the nervous  system  i s derived.  I t i s this  evidence that s t r o n g l y suggests that the r e g u l a r f u n c t i o n  of  the achaete-scute l o c u s i n v o l v e s the d i f f e r e n t i a t i o n of nerve elements. I n a r e c e n t s e r i e s o f s t u d i e s , t h e g e n e t i c and  develop-  m e n t a l c h a r a c t e r i s t i c s o f t h e a c h a e t e - s c u t e system have been investigated Bellido,  ( G a r c i a - B e l l i d o and S a n t a m a r i a , 1 9 7 8 ;  1979)-  Garcia-  I n the developmental s t u d i e s , the authors  d e f i n e d t h e p h e n o e f f e c t i v e p h a s e and d e f i n e d s p e c i f i c  pheno-  t y p e s i n g y n a n d r o m o r p h s and m i t o t i c r e c o m b i n a t i o n c l o n e s . The  developmental r e s u l t s suggest t h a t the normal  o f t h e a c h a e t e - s c u t e c o m p l e x i n v o l v e s two  functions;  v o l v e d w i t h the d i f f e r e n t i a t i o n o f the embryonic nervous  s y s t e m and t h e o t h e r i n v o l v e d w i t h  of a d u l t p e r i p h e r a l nervous The  function one i n -  central  differentiation  elements.  l e t h a l phase a s s o c i a t e d w i t h a c - s c d e f i c i e n c i e s were  d e t e r m i n e d by e x a m i n i n g v i a b i l i t y p u p a l and a d u l t s t a g e s .  a t t h e egg,  embryo,  larval,  I t i s evident t h a t a l l of the  defi-  c i e n c i e s a r e h e m i z y g o u s l e t h a l s b u t t h e r e a p p e a r s t o be  two  separate l e t h a l i t y p r o f i l e s d i s t i n g u i s h i n g the mutants.  One  g r o u p h a s b e e n shown t o be d e f i c i e n t f o r a r e g i o n known a s l e t h a l o f s c u t e ( 1 ' s c ) w h i c h maps p r o x i m a l l y f r o m t h e m a t i c b r e a k s o f s c u t e - 4 and i n v a r i a b l y embryonic The  o t h e r group  scute-Si.  euchro-  These i n d i v i d u a l s  l e t h a l s and a r e e n t i r e l y  scute  are  mutants.  shows d e f i c i e n c i e s f o r b o t h _sc and ac b u t  not  29.  1'sc  and d i e i n a d v a n c e d  s t a g e s o r e v e n emerge a s  debilitated  adults. These a u t h o r s a l s o n o t e d t h e c h a r a c t e r i s t i c motor p r o b lems a s s o c i a t e d w i t h a d u l t s u r v i v o r s c a r r y i n g the scute ciencies.  I t was  observed that I n ( l ) y ^ ^  f u l l y m o t i l e and f e r t i l e w h i l e s c  sc  n o n - m o t i l e and  The  s t r o n g l y ac and  sc.  w e r e o b s e r v e d t o emerge a n d r e m a i n  defi-  s c ^ males are 8  and D f ( l ) s c non-motile  immobile  are  individuals  on t h e f o o d , o r  f r e q u e n t l y , w e r e f o u n d t o d i e when a t t e m p t i n g t o emerge f r o m the  p u p a r i a l case.  T h i s abnormal  developmental phenotype  has  a l s o b e e n o b s e r v e d i n many o t h e r r e c o m b i n a n t s c o n s t r u c t e d from v a r i o u s scute i n v e r s i o n s Different lethal viability was  ( i n preparation).  d e f i c i e n c i e s were s t u d i e d f o r t h e i r  i n male s p o t s i n gynanders.  o b s e r v e d o v e r a l l a r e a s o f t h e e p i d e r m i s and  dorsal medial l i n e frequently. gynanders the  D e f i c i e n c y male  crossed the  H o w e v e r , t h e r e were no  o b s e r v e d t h a t had male d e f i c i e n c y t i s s u e  ventral medial l i n e ,  s u g g e s t i n g t h a t gynanders  vous t i s s u e of the d e f i c i e n c y type are i n v i a b l e 1950).  with ner-  (Poulson,  i n v o l v i n g the D f ( l ) s c u t e - 8 .  study are the  Garcia-Bellido  (1978) d e t e r m i n e d t h a t t h e l e t h a l i t y n o t due  flies  problems.  Of s p e c i a l i n t e r e s t t o t h i s  t i s s u e was  viable  crossing  I n t h e s e s t u d i e s , t h e r e w e r e a l s o a number o f  observed w i t h m o b i l i t y  tissue  experiments  and  Santamaria  associated w i t h scute-8/0  t o v a r i e g a t i o n o f t h e rRNA g e n e s b u t ,  rather variegation of a v i a b i l i t y  gene n e a r t h e b r e a k p o i n t  30.  of scute-8.  These a u t h o r s a l s o  established  genes d i s t a l  t o ac  f o r chaete d i f f e r e n t i a t i o n .  Studies  are  required  morph s t u d i e s .  Results  i n the  established  distal  scute  The allele  the  absence of b r i s t l e - a f f e c t i n g  genes  r e m o v a l , by m i t o t i c r e c o m b i n a t i o n , o f a w i l d  e f f e c t of the  and  phenotype of the  of the  l o c u s may  M e r r i a m , 1971c)•  The  the  initial  of the  be  complete  hours f o r the  as  (Garciawith  of these experiments i s the  authors  estimate  ac-sc complex o c c u r s p r i o r  t o 4-0 h o u r s p r e p u p a r i u m f o r m a t i o n f o r t h e p r i o r t o 16  may  r e s u l t i n g clones  From t h e i r s t u d i e s ,  function  type  i n development  phenomenon i n v o l v e d  s p e c i f i c developmental p r o f i l e  c a l l e d perdurance. that  This  ( G a r c i a - B e l l i d o , 1979)-  major f u n c t i o n  Bellido the  the  be  also  studied.  o f some g e n e s a f t e r a g i v e n p o i n t  h a v e no  gynandro-  p r e v i o u s e x p e r i m e n t s and  showed t h a t much l a r g e r d e f i c i e n c i e s c o u l d work a l s o  exam-  f r o m t h e s e e x p e r i m e n t s c o n f i r m e d much  data produced i n the  to  the  i n v o l v i n g m i t o t i c recombination permit the  i n a t i o n of t i s s u e clones normally l e t h a l  of the  t h a t none o f  macrochaetae  and  microchaetae.  T h e s e w o r k s h a v e u n c o v e r e d a number o f i n t e r e s t i n g o b s e r v a t i o n s r e l a t i n g to the t i o n s h i p has  been e s t a b l i s h e d  nervous t i s s u e d i s f u n c t i o n .  achaete-scute region. between the  A  scute mutants  This observation  is  tence of s u r v i v i n g mutant a d u l t s w i t h  severely  tor functions.  of the  original function  and  strongly  s u p p o r t e d by m i t o t i c r e c o m b i n a t i o n e x p e r i m e n t s and  The  rela-  the  exis-  abnormal  ac-sc  locus  mo-  31-  a p p e a r s t o "be e x e r t e d p r i o r t o p u p a r i u m f o r m a t i o n w i t h s e condary f u n c t i o n s appearing The d e v e l o p m e n t a l  somewhat l a t e r i n d e v e l o p m e n t .  a n a l y s i s of the scute mutation  has  p r o d u c e d many i n t e r e s t i n g r e s u l t s b u t i t h a s b e e n t h e f u n d a mental g e n e t i c a n a l y s i s o f t h i s l o c u s t h a t has generated majority of research interest. the  the  The o r i g i n a l d i s c o v e r y o f  s c u t e gene o c c u r r e d i n 1 9 1 6 " when B r i d g e s s t u d i e d t h e  occurrence  o f spontaneous mutants i n D r o s o p h i l a .  on t h e e f f e c t s o f X - r a y s t e n y e a r s l a t e r , M u l l e r  In studies isolated  a c o l l e c t i o n o f b r i s t l e v a r i a n t s w h i c h mapped t o t h e same locus.  From t h e s e v a r i a n t s , a g r o u p o f S o v i e t  separated  a specific  geneticists  s e t o f a l l e l e s which they termed  scute  ( s c ) a n d mapped t h e s e m u t a n t s t o t h e t i p o f t h e X-chromosome. I n v e s t i g a t i o n s of these  scute mutants r e v e a l e d t h a t  they  e x i s t e d a s a h e t e r o g e n e o u s g r o u p w i t h t h e common p h e n o t y p e of reduced  b r i s t l e number.  to i d e n t i c a l p o s i t i o n s , phenotype.  Although  a l l the a l l e l e s  mapped  each a l l e l e p r o v i d e d a c h a r a c t e r i s t i c  This information provided the f i r s t  indication  t h a t t h e component d i s s e c t i o n o f a gene c o u l d be p o s s i b l e . The s t u d y o f p a r t i a l c o m p l e m e n t a t i o n c o u l d p r o v i d e  evidence  of the complexity of the scute l o c u s . The S o v i e t g r o u p was t h u s p r o m p t e d t o a c c e l e r a t e t h e i r r e s e a r c h i n t o t h e s c u t e " a l l e l o m o r p h s " and g e n e r a t e d a l l e l e s by X - i r r a d i a t i o n o f standard et a l . ,  1928).  stocks  further  (Serebrovsky  S u b s e q u e n t r e s e a r c h i n t o t h e phenomenon o f  step-allelomorphism or partial-complementation provided the  32.  first  evidence f o r t h e e x i s t e n c e o f "complex" genes and p r o -  duced t h e f i r s t  l i n e a r gene map c o r r e l a t i n g a n i n t r a - g e n e  position with a specific of t h e i r 1.  function.  The p r e d o m i n a n t  results'  s t u d i e s c a n he s u m m a r i z e d a s f o l l o w s : a l a r g e number o f s c u t e a l l e l e s c a n be i d e n t i f i e d , each showing b r i s t l e r e d u c t i o n b u t d i f f e r i n g i n the s p e c i f i c  2.  l o c a t i o n o f phenotype.  studies of heterozygotes  indicate that  phenotypic  c h a r a c t e r i s t i c s common t o s c u t e a l l e l e s w i l l n o t complement, w h i l e d i s t i n g u i s h i n g - revert to wild 3-  characteristics  type.  there exists a series of allelomorphs that repres e n t a g r a d i e n t w i t h i n t h e s c u t e gene.  There i s  a t r a n s i t i o n from v e r y s i m i l a r a l l e l e s t o those t h a t show f e w s i m i l a r k.  characteristics.  comparison o f t h e v a r i o u s allelomorphs t h e d i s s e c t i o n o f t h e s c u t e gene i n t o a t i o n u n i t s o r "gene c e n t r e s . " o f t h e s e gene c e n t r e s w i l l in  facilitates complement-  The a r r a n g e m e n t  subsequently  result  t h e c o n s t r u c t i o n o f a l i n e a r map o f t h e s c u t e  gene. ( D u b i n i n , 1929b, 1930b, 1930d; A g o l , 1929; S h a p i r o , 1930; Serebrovsky, The  193°a).  accumulation  o f these  d a t a r e p r e s e n t e d a n enormous  b o d y o f work a n d when t h r e e p r o m i n e n t g e n e t i c i s t s t h e work, c o n f i d e n c e  criticized  i n t h e p r o j e c t was d r a m a t i c a l l y u n d e r -  33-  m i n e d and  i n v e s t i g a t o r s were a v e r s e  t o f u r t h e r s t u d i e s on  the complex s c u t e l o c u s . The  critics  sitivity  of the  of the  s c u t e mutants t o m o d i f y i n g f a c t o r s as  of the inadequacy Schultz  " c o m p l e x " gene t h e o r y c i t e d t h e  of the  sub-gene h y p o t h e s i s .  senevidence  Sturtevant  (1931) u t i l i z e d X - d u p l i c a t i o n s o f v a r i o u s s i z e s  cover the  scute-1  allelomorph.  The  authors  observed  to  variant  b r i s t l e phenotypes w i t h each d u p l i c a t i o n d e s p i t e the f a c t t h e d u p l i c a t i o n s were a p p a r e n t l y c a r r y i n g t h e w i l d t y p e allele. ent  I t seems p o s s i b l e t h a t t h e w i l d t y p e  on t h e - d u p l i c a t i o n may  be  subject to  T h i s seems more l i k e l y  in light  such  heterochro-  of the f a c t t h a t  These a u t h o r s  and  a l s o s t u d i e d the e f f e c t  a chromosome _2 d o m i n a n t g e n e , H a i r l e s s scute-1  these  "dominant" phenotype has been r e p o r t e d f o r s c u t e  since t h i s study.  the  scute  position-effect  s t u d i e s were b a s e d on d a t a o b t a i n e d e n t i r e l y f r o m m a l e s t h a t no  that  s c u t e gene p r e s -  v a r i e g a t i o n o w i n g t o t h e p r o x i m i t y o f t h e gene t o matin.  and  allele.  They o b s e r v e d  of  (H), w i t h r e s p e c t to  a r e d u c t i o n of  n o t p r e d i c t e d b y t h e " s u b - g e n e " t h e o r y and  bristles  concluded  t h e s e r e s u l t s undermined the whole l o g i c a l b a s i s of  that the  hypothesis. Goldschmidt  (1930)  and  (1935)  Child  also c r i t i c i z e d  the  w o r k on t h e b a s i s o f t h e o b s e r v e d  e f f e c t o f a number o f mod-  ifying factors.  t h a t the b r i s t l e s  scute-1  Child  determined  i n d i v i d u a l were t e m p e r a t u r e  temperatures,  different  sensitive.  g r o u p s o f b r i s t l e s were  At  i n the different  affected.  34.  It  was  not mentioned t h a t at a l l temperatures, the  a f f e c t e d b r i s t l e s p o s t u l a t e d f o r scute-1 A n o t h e r segment o f t h e scute-1  stock  critique  authors  remained a f f e c t e d .  i n v o l v e d a s e l e c t i o n from  a f f e c t to other b r i s t l e  suggested t h a t these  development of the b r i s t l e s  genome and  w o r k by  the S o v i e t g e n e t i c i s t s .  concluding  "...these  the  p a t t e r n of d i s t r i b u t i o n i n scute  scute  l o c u s as i n -  show t h a t t h e  the  opmental processes  and  i s b a s e d on n o t h i n g  i n the  does not  correspond  individual fly."  Soviet  concept  t h a n d i f f e r e n c e s i n t h e mean n u m b e r s , i n a g r o u p o f of d i f f e r e n t b r i s t l e s  the  genetic  Child dismisses  data  pres-  showed t h a t  i s dependent upon the  system as a whole r a t h e r t h a n m e r e l y the  of  groups.  results revealed  ence o f m o d i f i e r s e l s e w h e r e i n the  f e r r e d by  the  of a s e r i e s of mutants i n v o l v i n g r e d u c t i o n  single b r i s t l e s without The  major  of  more flies,  t o any  Although  develChild  d e m o n s t r a t e d t h a t a v a r i e t y o f f a c t o r s were i n v o l v e d i n t h e development of the b r i s t l e s , and  the  other  c r i t i c i s m s were l e s s e r  only c o n s t i t u t e d grounds f o r m o d i f i c a t i o n of the  original  hypothesis. Unfortunately, these  prominent g e n e t i c i s t s ,  were d i s c o n t i n u e d for  as a consequence o f t h e  and  f u r t h e r s t u d i e s of  t h i s mass o f d a t a h a s  over f o r t y years  without  Recent progress  i n the  Ratner,  197^)•  of  step-allelism  been  neglected  subsequent c o n s i d e r a t i o n . field  of molecular  e l u c i d a t e d a number o f c o m p l e x g e n e t i c 1964;  admonishment  loci  genetics  (Jacob  Methods of complementation,  and  has Monod,  recombin-  35-  a t i o n and  gene s e q u e n c i n g  have been u t i l i z e d  t i o n o f g e n e t i c t o p o g r a p h y and karyotes.  S i m i l a r techniques  c o n t r o l mechanisms i n p r o have o n l y v e r y r e c e n t l y been  u s e d t o s t u d y e u k a r y o t i c genomes b u t t h e  study of  m e c h a n i s m s and p r o p e r t i e s o f c o m p l e x l o c i refractory. loci  The  i n the d i s s e c -  rapid progress  control  r e m a i n s somewhat  i n the a n a l y s i s of complex  i n t h e p r o k a r y o t i c genome h a s  regenerated  interest  in  t h e phenomenon o f s t e p - a l l e l i s m a t t h e s c u t e l o c u s . R e c e n t s t u d i e s by a S o v i e t r e s e a r c h g r o u p i n d i c a t e  that  t h e p r e v i o u s r e s u l t s o b t a i n e d b y D u b i n i n ejb a l . , (1929) a r e in  a c c o r d w i t h an o p e r o n - l i k e s y s t e m , composed o f t h r e e  four cistrons,  each r e s p o n s i b l e f o r b r i s t l e  d e v e l o p m e n t on  d o m a i n o f t h e f l y ( F u r m a n e t a l . , 1979)-  specific  these authors  or  Originally,  s t u d i e d a group of r e c e n t l y i s o l a t e d  scute  m u t a n t s f o r c o n f i r m a t i o n o f t h e o r i g i n a l w o r k by D u b i n i n The  r e s u l t s a r i s i n g from the newly d e r i v e d l i n e s  a p p r e c i a b l y from the i n i t i a l mentation locus  tests resulted  s t u d i e s but  a  est a l .  differed  subsequent comple-  i n an i d e n t i c a l map  f o r the  scute  ( R a t n e r e t a l . , I969). :  The  a u t h o r s p r o p o s e d two  the complex n a t u r e each b r i s t l e  of the scute l o c u s .  grouping  groupings  The  two  model  recognizes cistron  second model c o r r e s p o n d s  the  with overlapping recognition sites within  the operator of the scute operon. between these  One  as r e p r e s e n t a t i v e o f a s i n g l e  w i t h i n the scute operon. bristle  o p e r o n - l i k e models t o e x p l a i n  I n order to  theses, the authors found  distinguish  i t necessary  to  36.  a s s i g n the  s c u t e m u t a n t s t o a number o f c a t e g o r i e s  a n t w i t h r e s p e c t t o known m o d i f y i n g phenotype  ( F u r m a n and  f o u r complementation groups, the modifying the  scute  This approach s u p p l i e d  each having unique responses  to  T h i s i s t h e b a s i c d a t a upon w h i c h  operon models are t e s t e d . The  of the to  factors.  f a c t o r s of the  1977)-  Ratner,  invari-  authors  then i n v e s t i g a t e d the e x p l i c i t  c o m p l e m e n t a t i o n g r o u p s by  modifying  f a c t o r s and  similarity t i o n s on ted  of each group  bristle  a n a l y s i s has  (Furman e t a l . ,  t y p e , a m a t r i x c a n be information.  that there are at l e a s t  scute l o c u s .  Evidence  mutaconstruc-  multifac-  suggesting also  suggests  i n d i c e s w i t h i n t h e m a t r i x and  the authors  blocks  have  a s t r o n g c o r r e l a t i o n between scute f u n c t i o n a l u n i t s  and  on t h e f l y  t h o r a x , head, s c u t e l l u m ) . The  e s s e n t i a l products  v a t i o n o f map  linearity,  respect to temperature tion  the  three, possibly four, invariant  the t o p o g r a p h i c a l arrangement o f the b r i s t l e s (i.e.  This  provided compelling evidence  a p o l a r s t r u c t u r e of the  found  bristles  or d i f f e r e n c e of the m a n i f e s t a t i o n s of the  each s p e c i f i c  of b r i s t l e  responses  U s i n g a computer a n a l y s i s i n v o l v i n g o n l y  which includes a l l a v a i l a b l e  torial  typical  f o c u s s i n g a t t e n t i o n on t h e  deemed p r o x i m a l t o t h e l i m i t s 1977a,b,c).  examining  boundaries  zygotes.  This study  the  and  of the v a r i a b i l i t y  of t h i s  r e s e a r c h are the  obser-  i n v a r i a n c e of the c l u s t e r s  s c u t e gene d o s a g e and  an  o f e x p r e s s i o n i n s c u t e gene  of mapping-invariants  of scute  with  explanaheterohas  37-  g r e a t l y expanded the t h i s locus. data  The  evidence supporting  research  has  a c o m p l e x gene  also furnished a  significant  h a s e and  a testable hypothesis  that provides  work f o r f i n e  structural analysis.  The  b a s e and  the  f u r t h e r t e s t i n g of the  use  fine  plex by  l o c u s has  the  revealed  a n a l y s i s of the r e s u l t s very  e a r l y S o v i e t w o r k e r s and  Bellido, there  genetic  1979).  The  1979)  .  locus.  a c h a e t e - s c u t e com-  s i m i l a r to those  their  successors  1930d; M u l l e r , 1955;  (Dubinin,  (Hw)  l o c u s t o an  scute-8  euchromatic break.  (1'sc),  has  been a s s i g n e d  (Garcia-  A  area very  The  of the  ments s u g g e s t s t h a t the mirror scute  p o s i t i o n of  close to  data  scute  sc  vere scute phenotype w h i l e mutant.  These p r o p o s a l s  system i s c o n s t r u c t e d  the  dis-  experias  lethal  a  of  Those r e a r r a n g e m e n t s  of the  1'sc  l o c u s have a  t h o s e b r o k e n more d i s t a l l y  of genetic  scute  .  compiled i n these  ( G a r c i a - B e l l i d o , 1979).  having breaks i n the p r o x i m i t y  of  4-  image d u p l i c a t i o n a t b o t h s i d e s o f t h e locus  the  r e g i o n d e l i m i t e d by  i n v e r s i o n s s c ^ and  o r g a n i z a t i o n of the  discussions  second l o c u s , l e t h a l  to the  ac-sc  Furman e t a l . ,  the  9 t a l breakpoints  reported  f u n c t i o n a l c i s t r o n s w i t h i n the  These s t u d i e s have a l s o a s s i g n e d  the H a i r y wing  scute  molecular  r e g i o n which i s e n t i r e l y c o n s i s t e n t w i t h previous subject  data  f i n d i n g s from these s t u d i e s i n d i c a t e t h a t  i s at l e a s t three  of the  ground-  topography of the  structural organization within this  More r e c e n t  the  of t h i s  gene w i l l u l t i m a t e l y l e a d t o a k n o w l e d g e o f t h e and  at  o r g a n i z a t i o n and  se-  are  less  function  38.  are  still  highly speculative  Very e a r l y i n the it  became v e r y  t y p e was terial  with  of the  1935)-  Upon a n a l y s i s o f t h e t h a t m o s t o f 'the  This  scute  observation  gene l o c u s  f o s t e r e d the  d i f f e r e n c e between t r u e mutations" w i t h i n the i n t e r e s t are  the  near the Muller  scute  and  t h i s thesis... the  Soviet  (1930b).  a  locus  scute  ma-  Patterson,  first  allele  studies  ( R a f f e l and  interest i n defining  series.  Muller,  Of p a r t i c u l a r phenotypic  1940;  Gersh,  breaks 1949;  1947).  scute-8  was  f o u n d by H. T.G.  mutants c e n t r a l to  were o r i g i n a l l y r e p o r t e d  characterized  f o u n d by  as  i n v e r s i o n s by  L e v y i n T e x a s i n 1932  Scute-V2  characterized  as  was  of the  by  Muller  Sinitskaya i n Leningrad i n  ( M u l l e r e t a l . , 1937)• was  a  "position effect  examining the  organization  and  their  1940).  r e a r r a n g e m e n t s w e r e c o n f i r m e d i n t h e s e chromosomes  1946  and  mutants,  a l l e l e s owed  ( R a f f e l and.Muller,  study i n v o l v i n g the  in  genetic  a number o f X i n v e r s i o n s w i t h  S c u t e - 4 and  Scute-L8  pheno-  reattachment i n the v i -  f r o m t h e s e s t u d i e s were the  g r o u p and  s c u t e - S i was The  with  Valencia,  Evolving  scute  scute  a v a i l a b l e scute  "gene m u t a t i o n s " and  original  changes a s s o c i a t e d  o f t e n the  series,  Muller, Prokofyeva  p h e n o t y p e t o chromosome b r e a k a g e and of the  allelomorph  1 9 3 0 a , b , 1932;  Muller,  P r o k o f y e v a , 1934;  and  became e v i d e n t  cinity  scute  a rearrangement of the  ( S e r e b r o v s k y , 1930;  Raffel, it  studies  await f u r t h e r i n v e s t i g a t i o n .  obvious to workers that  associated  1932b; M u l l e r  and  and  1934. during  X-heterochromatin  discovered  by  Valencia  a simple i n v e r s i o n i n  39-  M u l l e r ' s l a b i n 1947 of these s p e c i f i c  ( M u l l e r and V a l e n c i a , 194-7).  chromosome r e a r r a n g e m e n t s  The  report  p r o m p t e d a number  o f s t u d i e s i n v e s t i g a t i n g t h e r e l a t i o n s h i p b e t w e e n t h e map s i t i o n of the d i f f e r e n t  chromosome b r e a k s  and  the k i n d s  poof  s c u t e p h e n o t y p e a s s o c i a t e d w i t h them. A l t h o u g h many o f t h e p r e v i o u s l y showed g r e a t d i v e r s i t y  i n phenotypic  strong c o r r e l a t i o n observed inversions  studied scute  e x p r e s s i o n , t h e r e was  between t h r e e p a r t i c u l a r  ( R a f f e l and M u l l e r , 1 9 4 0 ) .  t h a t the phenotypic  expressions of scute-4,  The  i n g phenotypes.  similar  observed  scute-Si  and  o f t h e numerous o t h e r  authors a l s o a l l u d e d to the  between the s t r i k i n g l y  i n v e r s i o n s and  the  association correspond-  A t t h i s t i m e , s u c h o b s e r v a t i o n s were  p r e t e d as s t r o n g e v i d e n c e  of a novel phenotypic  as p o s i t i o n - e f f e c t v a r i e g a t i o n  a  scute  These a u t h o r s  s c u t e - L 8 w e r e more c o m p a r a b l e t h a n any scute mutations.  alleles  inter-  c h a n g e known  ( M u l l e r and P r o k o f y e v a ,  1934,  1935a).  Further i n v e s t i g a t i o n of these three s i m i l a r i n v o l v e d the study of the phenotypic recombinants suggested  o f t h e s e chromosomes.  e x p r e s s i o n observed R e s u l t s of t h i s  t h a t t h e p h e n o t y p e s w e r e much a l i k e , b u t  d i f f e r e n t to unambiguously c h a r a c t e r i z e evidence  accumulated  in  technique sufficiently  e a c h chromosome.  s t r o n g l y i n d i c a t e s t h a t both  of the i n v e r s i o n a f f e c t  scutes  The  breakpoints  the development of the b r i s t l e s a l -  though the d a t a demonstrates  t h a t the i n f l u e n c e s of the  r e g i o n s are c l e a r l y the p r e v a l e n t source  left  o f t h e s c u t e pheno-  40.  t y p e ( R a f f e l a n d M u l l e r , 194-0). Another important mination  result o f t h i s research  o f a phenotypic  "gradient."  Wherever  d i f f e r e n c e s were o b s e r v e d between t h e s e  was t h e d e t e r significant  s t o c k s , t h e most  s e v e r e p h e n o t y p e was a l w a y s o b s e r v e d i n t h e s c u t e - L 8 while  stock  t h e s c u t e - 4 - s t o c k was l e a s t a f f e c t e d a n d s c u t e - S i was  intermediate  i n phenotype.  I t was o b s e r v e d t h a t t h e s e  mu-  t a n t s p r i m a r i l y a f f e c t e d those b r i s t l e s t h a t p r e v i o u s l y had been a s s o c i a t e d w i t h t h e scute  locus  ( D u b i n i n , 1930d).  Those  b r i s t l e s a s s o c i a t e d with t h e achaete locus a r e l a r g e l y unaff e c t e d w i t h one m a j o r e x c e p t i o n .  The v e n t r a l a n d d o r s a l  s t e r n i t e s were s u b s t a n t i a l l y a f f e c t e d a n d showed t h e d i s t i n c t i v e phenotypic  s e r i e s mentioned above.  d i f f e r e n c e between t h e s t o c k s p r o v i d e d  This very a convenient  obvious phenotypic  c h a r a c t e r w i t h w h i c h t h e s t o c k s c o u l d be d i f f e r e n t i a t e d . I t has p r e v i o u s l y been determined t h a t t h e rearrangements i n these the  t h r e e m u t a n t s do n o t a c t u a l l y a l t e r t h e p o s i t i o n o f  scute l o c u s , t h e r e f o r e , the euchromatic breaks are a l l  proximal 1934,  with respect  1935a).  t o t h e centromere ( M u l l e r and P r o k o f y e v a ,  I t seems r e a s o n a b l e  t o presume t h a t t h e s c u t e  phenotype i s a r e s u l t o f a d i s r u p t i o n o f t h e f u n c t i o n o f t h e s c u t e gene a n d t h i s must a r i s e a s a c o n s e q u e n c e o f t h e a l t e r e d chromosomal c o n s t i t u t i o n i n t h e p r o x i m i t y o f t h e scute  locus.  T h i s c o n c l u s i o n was a l s o r e a c h e d b y M u l l e r a n d P r o k o f y e v a (1934) who f i r s t  suggested t h a t t h e phenotypes e x h i b i t e d by  s c u t e - 4 a n d s c u t e - L 8 were a r e s u l t o f " p o s i t i o n e f f e c t . "  The  41.  euchromatic almost  " b r e a k p o i n t o f t h e s e t h r e e i n v e r s i o n s must he  i d e n t i c a l as a l l o f t h e recombinants  t h e s t o c k s a r e v i a b l e and f e r t i l e .  c o n s t r u c t e d from  Should the breakpoints  d i f f e r w i t h r e s p e c t t o a n y e s s e n t i a l g e n e , one o f t h e r e c o m b i n a n t s w o u l d be s t e r i l e  or l e t h a l .  Authors  have t h u s  gested t h a t the phenotypic d i f f e r e n c e s observed  sug-  i n these  stocks are a r e s u l t of the d i f f e r i n g breakpoints i n the proximal heterochromatin of  ( R a f f e l and M u l l e r , 1 9 4 0 ) .  Discussion  t h e e f f e c t s o f d i f f e r e n t a r e a s o f h e t e r o c h r o m a t i n and  t h e i r r e l a t i o n s h i p to p o s i t i o n - e f f e c t v a r i e g a t i o n are presented elsewhere  i n the text.  The two o t h e r i n v e r s i o n s s i g n i f i c a n t t o t h i s s t u d y a r e s c u t e - V 2 and s c u t e - 8 .  F a r l e s s e f f o r t has been expended t o  study t h e scute phenotype i n these i n d i v i d u a l s as a r e s u l t of  the o r i g i n a l r e p o r t s which  suggested  that the b r i s t l e  p h e n o t y p e was i r r e g u l a r a n d u n p r e d i c t a b l e ( S i d o r o v , 1931; Prokofyeva-Belgovskaya, of  1947; G e r s h ,  1949).  The  instability  t h e phenotypes has been r e c e n t l y c o r r o b o r a t e d i n a  i n v o l v i n g the complementation ( F u r m a n jet a l . , 1 9 7 9 ) -  study  groups o f the scute l o c u s  I n many s i t u a t i o n s , f l i e s  carrying  t h e s e i n v e r s i o n s p r o d u c e a c c e s s o r y m a c r o c h a e t a e a t some w h i l e reduced  number o f m a j o r b r i s t l e s o c c u r a t o t h e r  There i s a l s o profound v a r i a t i o n o f the microchaetae appears  sites  sites. which  t o be a t t r i b u t a b l e t o a p o s i t i o n e f f e c t on t h e a c h a e t e  locus. The o r i g i n a l  s t u d i e s o f u s i n g scute-8 i n v o l v e d a study  42.  of the exact  l i m i t s o f t h e i n v e r s i o n ( P a t t e r s o n , 1932b).  f a c t that the heterochromatic  The  p o r t i o n of the inversion carried  t h e b o b b e d r e g i o n and t h a t a l l e u c h r o m a t i c g e n e s p r o x i m a l the  s c u t e l o c u s w e r e i n v e r t e d was e s t a b l i s h e d b y r e c o m b i n a n t ( P a t t e r s o n , 1932b).  analysis  euchromatic break i n scute-8 and  to  achaete,  centromeric  I t was a l s o shown t h a t t h e occurred  between the l o c i  scute  with the scute locus being r e l o c a t e d to the end o f t h e X-chromosome ( P a t t e r s o n and S t o n e ,  1934).  In scute-8  the study  of mosaic f o r m a t i o n  ( P a t t e r s o n , 1933)>  m a l e s w e r e X - r a y e d a n d i t was f o u n d t h a t t h e r e g i o n  extending  from the l e f t  b r e a k t o t h e t i p c o u l d be e l i m i n a t e d .  This created a d e f i c i e n c y f o r those the t i p .  loci  b e t w e e n a c h a e t e and  These a b e r r a t i o n s were i d e n t i f i e d  as y e l l o w hypo-  p l o i d f e m a l e s and were t h e n mated t o bobbed m a l e s i n an e f f o r t t o d e m o n s t r a t e t h e p o s i t i o n o f t h e bobbed l o c u s i n t h e inversion.  Of p a r t i c u l a r  i n t e r e s t t o t h i s p a p e r i s t h e ob-  servation that the great majority of breaks occurred t h e l o c u s o f y e l l o w and b o b b e d w h i c h i n d i c a t e s t h a t  between there  m u s t be a c o n s i d e r a b l e p i e c e o f p r o x i m a l  heterochromatin  l o c a t e d t o t h e t i p o f t h e X-chromosome.  The u s e o f a  technique  to characterize the heterochromatic  the v a r i o u s scute  similar  breakpoints  of  inversions i s presently i n progress.  The i r r a d i a t i o n o f t h e s c u t e - 8 heterochromatic  re-  males a l s o produces  d u p l i c a t i o n s c a r r y i n g the w i l d type  y e l l o w a n d a s m a l l number o f o t h e r  euchromatic l o c i .  small  allele These  of  ^3.  r e s u l t f r o m two h e t e r o c h r o m a t i c  b r e a k s and. e l i m i n a t i o n o f  the m a j o r i t y o f the X-euchromatin. e x p e r i m e n t , one w o u l d e x p e c t y e l l o w and t h e bobbed l o c u s .  Based upon t h e p r e v i o u s  most b r e a k s t o o c c u r  between  The r e a s s o c i a t i o n o f t h e c h r o -  mosome p i e c e s s h o u l d p r o d u c e d u p l i c a t i o n s c a r r y i n g no b o b b e d locus.  R a r e l y , one s h o u l d r e c o v e r a d u p l i c a t i o n c o n t a i n i n g  a n o r m a l bobbed l o c u s w h i c h r e s u l t e d from a  heterochromatic  b r e a k t o t h e r i g h t o f t h e bobbed l o c u s and a n o t h e r the centromeric  region.  break i n  The r e s u l t s o f P a t t e r s o n a n d S t o n e  (1935) a r e i n d i r e c t c o n f l i c t w i t h t h i s r e a s o n i n g .  Although  87$ o f a l l . b r e a k s o c c u r r e d b e t w e e n t h e y e l l o w l o c u s a n d t h e bobbed l o c u s i n t h e f i r s t  experiment, t h e d u p l i c a t i o n exper-  i m e n t s i n d i c a t e t h a t o n l y 8% o f t h e b r e a k s o c c u r region. The  The a u t h o r s  d i d n o t comment on t h i s  i n this  discrepancy.  d u p l i c a t i o n experiments also e s t a b l i s h e d that the  euchromatic breakpoint s c u t e and a c h a e t e l o c i .  i n s c u t e - 8 was l o c a t e d b e t w e e n t h e T h i s r e s u l t i s b a s e d upon t h e ob-  s e r v a t i o n that the scute locus i s always a s s o c i a t e d w i t h the rearranged  genes i n t h e c e n t r o m e r i c  region.  I n contrast,  t h e achaete l o c u s i s always a s s o c i a t e d w i t h t h e genes ing  retain-  t h e i r n o r m a l s e q u e n c e n e a r t h e t i p o f t h e chromosome.  T h i s work f i r s t  demonstrated the d i v i s i b i l i t y  s c u t e complex and t h a t t h e a c t i o n o f t h e s e  o f the achaete-  genes were n o t  cis-contiguous. The in  e x p r e s s i o n o f p o s i t i o n e f f e c t s has a l s o been s t u d i e d  scute-8 w i t h r e l a t i o n s h i p t o t h e h e t e r o c h r o m a t i z a t i o n o f  44.  euchromatic Many a u t h o r s euchromatic opposing  loci  have s u g g e s t e d  genes a r e a r e s u l t  heterochromatin  of a "spreading  ( S c h u l t z , 194l;  fect and  i s m a x i m i z e d a t 25°C w h i l e l4°C  suggest  loci  rearrangement i s temperature  sensitive.  1947)•  of temperature  1949).  JO°C  observations  to the  The s t u d y i n v e s t i g a t e d t h e e f f e c t  on t h e v a r i e g a t i n g e x p r e s s i o n o f t h e H a i r y i n the scute-8  i n p o l y t e n e b a n d s 1B1.2  inversion.  The  t o 1 B 3 . 4 ( L i n d s l e y and  1968) w h i c h a r e v a r i a b l y h e t e r o c h r o m a t i z e d scute-8  at  e x p r e s s i o n o f v a r i e g a t i n g g e n e s known t o  w i n g and s c u t e m u t a t i o n s reside  The e f -  T h i s s t r a t e g y was  r e s i d e i n the v a r i a b l y condensed r e g i o n s adjacent (Gersh,  1976).  associated with  p u r s u e d f u r t h e r by c o r r e l a t i n g t h e c y t o l o g i c a l  breakpoints  of the  that  s i g n i f i c a n t l y reduced  (Prokofyeva-Belgovskaya,  with the phenotypic  effect"  S p o f f o r d , 1959.  chromosomes  h e t e r o c h r o m a t i z a t i o n of the euchromatic scute-8  1949).  Gersh,  that the p o s i t i o n e f f e c t s of  C y t o l o g i c a l studies of polytene  the  194?;  (Prokofyeva-Belgovskaya,  grown a t d i f f e r e n t t e m p e r a t u r e s .  genes  Grell,  i n stocks of Gersh  (1949)  theor-  i z e d t h a t i f t h e r e e x i s t s a d i r e c t r e l a t i o n s h i p between p o s i t i o n e f f e c t a n d h e t e r o c h r o m a t i z a t i o n , one s h o u l d be a b l e t o r e g u l a t e t h e e x p r e s s i o n o f a v a r i e g a t i n g gene b y the  altering  extent o f h e t e r o c h r o m a t i z a t i o n w i t h temperature  Prokofyeva-Belgovskaya  (1945)  observed  c h r o m a t i z a t i o n a t 25° a n d a r e d u c e d treme temperatures.  change.  a maximum o f h e t e r o -  e f f e c t a t t h e more ex-  One w o u l d e x p e c t  s i o n o f t h e m u t a n t s t o be m o s t s e v e r e  the phenotypic a t 25° and l e s s  expresdrama-  45-  tic  at other  temperatures.  The d a t a ,  however, suggest  an i n v e r s e r e l a t i o n s h i p e x i s t s between b r i s t l e and t e m p e r a t u r e , t h e r e f o r e t o r s are not c l a s s i c a l l y  that  expression  implying that the b r i s t l e  variega-  affected or that the r e l a t i o n s h i p  between h e t e r o c h r o m a t i z a t i o n  and p h e n o t y p i c e x p r e s s i o n i n -  v o l v e s more t h a n m e r e l y t h e c o n d e n s a t i o n o f p r e v i o u s l y matic s i t e s .  S i m i l a r r e s u l t s are reported  who s t u d i e d t h e b r i s t l e tem.  expression  by C h i l d  (1935)  i n a non-variegating  I t seems l i k e l y t h a t t h e m a n i f e s t a t i o n  as  sys-  of b r i s t l e  t y p e s a s a r e s u l t o f p o s i t i o n e f f e c t may i n v o l v e many o f b r i s t l e -development.  euchro-  phenosteps  S u c h a c o m p l e x s y s t e m may n o t r e a c t  e x p e c t e d when s u b j e c t e d  to classical  t e s t s of p o s i t i o n -  effect variegation. A n o t h e r o f t h e s i g n i f i c a n t phenomena a s s o c i a t e d w i t h t h e scute  i n v e r s i o n s i s the maternal e f f e c t which r e s u l t s i n  g r e a t l y i n c r e a s e d v i a b i l i t y o f s c u t e X/0 m a l e s ( J o h n s o n , Generally,  t h e v i a b i l i t y o f s c u t e X/0 i n d i v i d u a l s i s a p p r o x i -  m a t e l y 10% o f c o n t r o l s when t h e s c u t e from t h e male p a r e n t .  inversion i s inherited  When t h e same s c u t e X-chromosome i  i n h e r i t e d from the female parent, ten-fold.  1979)-  s  t h e v i a b i l i t y i s enhanced  The b a s i s o f a l l m a t e r n a l e f f e c t s i s t h e d i f f e r e n c e  i n phenotype o f g e n e t i c a l l y i d e n t i c a l i n d i v i d u a l s as a r e s u l t of the parental  s o u r c e o f t h e chromosomes.  Reciprocal crosses  have o f t e n been o b s e r v e d t o p r o d u c e  d i f f e r e n t r e s u l t s and c l a s s i c a l r e s u l t s as evidence s u p p o r t i n g  a n a l y s t s have q u o t e d cytoplasmic  such  inheritance.  46.  There are  obvious f a l l a c i e s with  adequately dealt with t a n c e has  s i n c e the  been adopted.  t h i s theory  chromosomal t h e o r y  I n more r e c e n t  h a v e b e e n more i n t e r e s t e d i n t h e a c r u e d by the  egg  transmission  or  The  t h a t have been of  years, g e n e t i c i s t s  d i f f e r e n c e s i n phenotype  of i d e n t i c a l  hereditary material via  sperm.  first  i n d i c a t i o n s of p a r e n t a l m o d i f i c a t i o n s  t y p e t h a t were a s s o c i a t e d w i t h p o s i t i o n e f f e c t can t o i n v e s t i g a t i o n s of the  white-mottled w /w m  (w_^)  Schultz  (194-1) who  T h i s was  and  a l s o the  yellow  s c u t e - 8 i n v e r s i o n and  paternal  a n d  w a s  v e r s i o n was  transmitted-from  transmitted  through the  v a r i e g a t i o n was  forma-  eyes than  Noujdin  the by  associated  established specific  maternal  Noujdin determined  r e d u c e d when t h e  He  (1)  (1941)  achaete l o c i  the mother but  father.  In  h o m o z y g o t e s a l w a y s show  and  e f f e c t s f o r both l o c i .  v a r i e g a t i o n o f b o t h x.  traced  case observed  heterozygotes.  s t u d i e d v a r i e g a t i o n of the the  lighter  remarked t h a t the  more v a r i e g a t i o n t h a n t h e  with  be  S l i z y n s k a noted t h a t the  h o m o z y g o t e s had  heterozygotes.  of pheno-  fundamental b a s i s of mosaic  I n 1 9 3 7 i Demerec and  tion.  inheri-  that  scute-8 i n -  increased  also determined  when  that  more e x t r e m e i n m a l e p r o g e n y f r o m h e t e r o z y g o u s  females. To  date,  t h e most e x t e n s i v e l y s t u d i e d m a t e r n a l e f f e c t s  have been t h o s e a s s o c i a t e d w i t h maroonlike  (mal)  and  h a v e b e e n many o t h e r s  the  tumerous head  the w h i t e - m o t t l e d described  i n the  (w^)  (tuh),  mutants.  literature  There  as f o l l o w s :  47-  and W i l l i a m s o n , 1 9 7 6 ) ; d a u g h t e r l e s s  cinnamon ( c i n ) - (Browder (da) - ( C l i n e ,  1976);  deep o r a n g e  maternal effect l e t h a l abnormal oocyte  (mat(3)  1977);  et a l . ,  1975);  - ( R i c e and G a r e n ,  - ( S a n d l e r , 1970)  (abo)  unnamed m u t a n t s ( M o h l e r , The  3)  (dor) - (Marsh  and many o t h e r  1976).  most o b v i o u s d i f f e r e n c e between p a r e n t a l s o u r c e s  genes i s the environment o f t h e egg c e l l  o f t h e gamete.  Physically,  i s many t i m e s t h a t o f t h e sperm and  t e n t s a r e f a r more c o m p l e x .  E a r l y embryonic  the the  of size  con-  development i s  m a i n t a i n e d by t h e l a r g e amount o f c y t o p l a s m w h i c h c o n t a i n s p r o d u c t s o f t h e m a t e r n a l genome.  Thus, e a r l y  embryogenesis  i s p r o f o u n d l y i n f l u e n c e d by t h e c h a r a c t e r o f t h e genome a n d  cytoplasm  maternal  ( K h e s i n , 194-7; D a v i d s o n , 1 9 7 6 ) .  More r e c e n t i n v e s t i g a t i o n s o f t h e s e t y p e s o f m a t e r n a l . e f f e c t s i n d i c a t e t h a t t h e phenomenon may  be  due  to  proteins  o r mRNAs r e s u l t a n t f r o m t h e o o c y t e m a t u r a t i o n p r o c e s s and  Shaw, 1970;  Hough-Evans e t a l . ,  1977).  Exclusive  (Wright protein  s y n t h e s i s f r o m m a t e r n a l t e m p l a t e h a s b e e n shown f o r some o f the p r o d u c t s e s s e n t i a l i n e a r l y embryogenesis 1972;  L i f t o n and K e d e s , 1 9 7 6 ) .  ( R a f f e_t a l . ,  L o n g - l i v e d , s t a b l e mRNA m o l e -  c u l e s c o d i n g f o r a number o f m a t e r n a l enzymes h a v e a l s o discovered opmental  (Gerasimova  and  Smirnova,  1980).  phenomenon o f m a t e r n a l e f f e c t  been  Thus, the d e v e l -  i s based upon the  e q u a l c o n t r i b u t i o n o f m a t e r i a l t o t h e z y g o t e by t h e egg  unand  sperm. The  g e n e t i c phenomenon o f m a t e r n a l e f f e c t  i s less  well  4-8.  d e f i n e d b u t may w e l l be i n t i m a t e l y opmental p r o c e s s e s p r e v i o u s l y have s t u d i e d  associated  discussed.  with the  Most  experiments  the d i f f e r e n t l e v e l s of variegating  r e s u l t i n g from a d i f f e r e n t p a r e n t a l  devel-  phenotype  source o f the rearrange-  ment ( L u n i n g , 1954; S p o f f o r d , 1958; H e s s l e r ,  1961).  These  e x p e r i m e n t s were u n d e r t a k e n t o d e t e r m i n e w h e t h e r t h e i n f l u ential factor  involved  w i t h g e n e t i c m a t e r n a l e f f e c t s was t h e  chromosomal c o n s t i t u t i o n o r t h e mechanism via  transmission  e g g o r v i a sperm. (1961)  Spofford  observed strong parental  study of white-mottled variegation. a small  X-chromosome d u p l i c a t i o n  white locus.  The f r e e  that  duplication  d u p l i c a t i o n was t r a n s l o c a t e d  effects i n the  The e x p e r i m e n t s carried a  yielded  l e s s m u t a n t p h e n o t y p e when t r a n s m i t t e d the  of  a  involved  variegating  significantly  t h r o u g h t h e egg.  When  i n t o an autosomal e n v i r o n -  m e n t , h o w e v e r , t h e o p p o s i t e r e s u l t was o b s e r v e d :  i . e . the  m o s t w i l d t y p e p h e n o t y p e was o b s e r v e d when t h e d u p l i c a t i o n was t r a n s m i t t e d  v i a t h e sperm.  these r e s u l t s considering  I t was d i f f i c u l t  t h e number o f f a c t o r s t h a t a r e  known t o a f f e c t p o s i t i o n - e f f e c t v a r i e g a t i o n . that  these data are uniquely a f u n c t i o n  or a p h y s i o l o g i c a l mechanism  phenomenon t h a t  of position  to interpret  effect.  I t i s possible  of the white  i s associated  locus  with the  T h e s e e x p e r i m e n t s do n o t d e -  t e r m i n e a g e n e r a l r e l a t i o n s h i p between m a t e r n a l e f f e c t s and position-effect variegation new v a r i e g a t i n g  a n d i t w i l l be n e c e s s a r y t o  maternal e f f e c t mutants t o e s t a b l i s h  define  this  49.  association.  The the  o r i g i n a l purpose of t h i s  s t u d y was  p o s i t i o n e f f e c t l e t h a l i t y t h a t was  s c u t e i n v e r s i o n X/0 (1962) t h a t  condition.  s c u t e - 8 and  I t was  to  investigate  associated  with  d e t e r m i n e d "by H e s s  Base males e x h i b i t e d g r e a t l y  v i a b i l i t y when l a c k i n g a Y-chromosome. m e n t s , H e s s showed t h a t  the  the  reduced  In p a r a l l e l  experi-  s c u t e males were r e s c u e d i n  the  p r e s e n c e o f a Y-chromosome o r a number o f Y-chromosome f r a g ments. with  Hess p o s t u l a t e d  that  the  a p o s i t i o n e f f e c t of the  genes i n the  euchromatic b r e a k p o i n t of the From t h e an ity  scute  r e s u l t s of a l a t e r  alternative interpretation. o b s e r v e d i n s c u t e X/0  s u p p r e s s i o n of the bance of the point.  m a l e s was  Baker's f i n d i n g corroborated  made by H e s s and  extended the  of  the  inversions. (1971)  offered  suggested t h a t the due  of the the  study to  lethal-  to a p o s i t i o n e f f e c t  genes r a t h e r  proximity  associated  proximity  study, Baker He  r i b o s o m a l RNA  genes i n the  l e t h a l i t y was  than a d i s t u r -  euchromatic  original  include  break-  observations  other  scute  inversions. I n an  e f f o r t to  genes i n the  study the  vicinity  of the  c o n t r i b u t i o n of  breakpoints,  Baker u t i l i z e d  d u p l i c a t i o n s w h i c h were g e n e r a t e d from the mosome.  Baker observed t h a t a l l of the  increased inversions  viability  i n the  s c u t e - 8 and  variegating  t i p of the  X-chro-  scute i n d i v i d u a l s  presence of the  duplications.  scute-V2 were e x c l u d e d from  small  had The  consider-  50.  ation after t h i s point  a s t h e i r v i a b i l i t y was  h a n c e d by t h e d u p l i c a t i o n s . scute-8/0  and  scute-V2/0  i n the presence  greatly  However, t h e v i a b i l i t y  males never r e t u r n s  of the  to c o n t r o l l e v e l s  o f t h e d u p l i c a t i o n s and t h e a u t h o r d o e s n o t  comment on t h i s d i s c r e p a n c y .  The  d a t a prompted Baker  to  8  elude that the l e t h a l i t y a s s o c i a t e d individuals located The  was  with  a r e s u l t of a l e t h a l  remaining scute inversions,  the d u p l i c a t i o n s .  V 2  s c / 0 and  the l e t h a l i t y  The  observed w i t h  by g e n e s l o c a t e d  scute-Si  in viability  insensitivity  these X/0  i n association o f t h e s e two  m a l e s must be  a t t h e b a s e o f t h e X-chromosome.  Y-chromosome p r o m p t s two  The  l i n e s of thought.  r e s u l t from the v a r i e g a t i o n  o f t h e Y-chromosome o r c o m p l e m e n t a t i o n bobbed l o c u s  Baker used  sc  of the  r e s u l t s suggest that  The  re-  normal  locus.  hypotheses, which  carried  rDNA.  the v i a b i l i t y  o f sc  O  "I  / 0 d i d not r e t u r n to c o n t r o l values i n the presence  many Y - c h r o m o s o m a l f r a g m e n t s the r i b o s o m a l genes.  Baker  which  via-  variegating  a number o f Y - c h r o m o s o m a l f r a g m e n t s  Baker's  caused  suppressing action  b e t w e e n t h e s e two  a m o u n t s o f h e t e r o c h r o m a t i n and  that  rescued  by t h e s t a n d a r d Y-chromosome b o b b e d  I n an e f f o r t t o d i s c r i m i n a t e  geno-  suggesting  of a  b i l i t y may  scute-L8,  and  covery of these i n d i v i d u a l s i n the presence  L8  /0  sc  s u p p r e s s i o n o f genes  types to the d u p l i c a t i o n s p r o v i d e d evidence  varying  con-  a t t h e t i p o f t h e X-chromosome.  showed o n l y a m o d e s t i n c r e a s e with  en-  lack a f u l l  /0  or  of  complement o f  i n t e r p r e t s these d a t a as  suppor-  51.  t i v e of a hypothesis of suppression of the ribosomal  cistrons.  T h e r e a r e many f l a w s a s s o c i a t e d w i t h t h e e x p e r i m e n t a l methods i n t h e s e  studies.  The d a t a w e r e a l l c o l l e c t e d  one-way c r o s s e s a n d a number o f d i f f e r e n t compound somes w e r e u s e d t h r o u g h o u t fragments  the studies.  from  X-chromo-  The Y - c h r o m o s o m a l  have n o t been a c c u r a t e l y d e f i n e d as t o t h e i r  erochromatic  c o n t e n t a n d t h e rDNA r e d u n d a n c i e s  termined p r i o r to the experiments. i n c r e a s e s i n X/0 v i a b i l i t y  het-  were n o t de-  I t i s apparent  that large  are associated with the heterochro-  m a t i c d u p l i c a t i o n s a n d one must c o n s i d e r o t h e r s o u r c e s o f l e t h a l i t y t o account  f o r the d i s c r e p a n c i e s i n these  exper-  iments. The t h i r d p a r t o f B a k e r ' s viability  a s s o c i a t e d w i t h recombinants  inversions.  of the various scute  The i n v e s t i g a t i o n f o c u s s e d u p o n t h e v i a b i l i t y  t h e s c u t e X/0 r e c o m b i n a n t s extent of heterochromatic ation.  study i n v o l v e d a r e p o r t of the  of  with p a r t i c u l a r reference to the a n e u p l o i d y r e s u l t i n g from  recombin-  The i n t e r p r e t a t i o n o f t h e s e r e s u l t s i s n e c e s s a r i l y  s p e c u l a t i v e as the d e f i n i t i o n o f the h e t e r o c h r o m a t i c i n t h e s c u t e i n v e r s i o n s h a s b e e n somewhat major o b j e c t i v e of the present numerous s h o r t c o m i n g s  breaks  subjective.  s t u d i e s has been t o  i n t h e "unambiguous" e v i d e n c e  The  illustrate presented  by B a k e r and t o p r e s e n t d a t a s u p p o r t i n g an a l t e r n a t i v e  hypoth-  esis. A number  of authors provided biochemical evidence  sup-  p o r t i n g t h e s u p p r e s s i o n o f rRNA i n s c u t e - S i i n d i v i d u a l s .  52.  (1973) i n v e s t i g a t e d t h e  Nix  rRNA q u a n t i t i e s p r e s e n t i n  S1 sc  /O  larvae.  the  18s  and  Nix  28s  /0  rRNA i n sc  third  author a l s o e s t a b l i s h e d that the a full  15$  reported a consistent SI  reduction  instar larvae.  scute-Si  The  chromosome r e t a i n e d  c o m p l e m e n t o f rDNA by RNA:DNA h y b r i d i z a t i o n .  gested t h a t the  decreased synthesis  of t r a n s c r i p t i o n of the  disturbances  biochemical  development.  rDNA  15  - 20$  or  processes involved  d e c r e a s e i n rRNA c o n t e n t b u t  mention the v i a b i l i t y associated S1 f a c t t h a t the  /0  sc  with  with  v i n c i n g evidence that the  does  associated  T h e s e d a t a do n o t  reduction  show not  these i n d i v i d u a l s or  i n d i v i d u a l s are not  bobbed phenotype.  sug-  re-  N i x m e n t i o n s t h a t e x t r e m e l y bobbed f l i e s  a consistent  detectable  Nix  of ribosomes could  s u l t from suppression of other  of  with  produce  o f rRNA c o n t e n t  the  a con-  in  SI sc in  /0  larvae  i s c a u s a l l y r e l a t e d to the  lethality  observed  adults. I n a s e r i e s o f s t u d i e s o f rRNA s y n t h e t i c r a t e ,  and  S n y d e r (1973)  d e m o n s t r a t e d a 10$  reduction S1  XJ8  m a t u r e o o c y t e s f r o m homozygous sc to the is  developmental delay  entirely likely  from experimental bias. an  t h a t the and  w i t h rRNA. contain  associated  The  females.  Owing  w i t h these females, i t eggs  c o n t r o l i n d i v i d u a l s would r e s u l t i n a c o n t r o l sample would  eggs w h i c h have been m a x i m a l l y SI  sample o f eggs from the  l e s s s t a g e 14  o f rRNA i n  simultaneous sampling of  I t i s p o s s i b l e that the  e x c e s s o f s t a g e 14  o r sc  Puckett  e g g s and  sc  female  contain supplied could  c o n s e q u e n t l y , l e s s rRNA.  53-  I n a s u b s e q u e n t p a p e r , P u c k e t t and  S n y d e r (1973a)  repor-  Sl /0 m a l e e m b r y o s had  t e d t h a t sc  rRNA d u r i n g t h e f i r s t a n o r m a l r a t e was  g r e a t l y reduced  synthesis of  f i v e hours of embryogenesis a f t e r  established.  be a l t e r e d by a s i m p l e  Again,  sample b i a s .  these  which  experiments  may  E g g s were s e l e c t e d e a r l y  i n d e v e l o p m e n t and  samples were removed a t d i f f e r e n t d e v e l o p S1 m e n t a l s t a g e s up t o t h i r d i n s t a r . The s a m p l e o f sc / 0 e m b r y o s c o n t a i n e d a l l i n d i v i d u a l s t h a t were o f t h i s genotype. There i s a s i g n i f i c a n t l e t h a l i t y a s s o c i a t e d w i t h the embryonic phase SI and  the  sc  /0  g e n o t y p e and  t h u s , samples taken i n the  s t a g e s r e p r e s e n t a h i g h l y s e l e c t e d sample.  The  larval  comparison  SI /0  o f e m b r y o n i c sc t o show s u c h  c o n t r o l i n d i v i d u a l s w o u l d be  a d i f f e r e n c e should the inherent scute  r e s u l t i n reduced r e s u l t s may  and  be  rRNA c o n t e n t  i n t h e embryo.  Thus,  e x p l a i n e d i n terms of a b a s i c d e f e c t  expected defect these associ-  ated w i t h the s c u t e - S l i n v e r s i o n . While  s t u d y i n g t h e s e g r e g a t i o n o f compound a u t o s o m e s ,  H a r g e r (1974) o b s e r v e d s c u t e X/0 source  a marked i n c r e a s e i n the v i a b i l i t y  i n d i v i d u a l s w h i c h was  of rearrangement.  of  dependent upon the p a r e n t a l  This maternal  effect  suppression  o f t h e l e t h a l i t y p r o v i d e s an e n t i r e l y n o v e l a p p r o a c h t o  the  s t u d y o f t h e phenomena a s s o c i a t e d w i t h t h e s c u t e i n v e r s i o n s . T h e s e s t u d i e s may  also provide further insight into  m e c h a n i s m s o f p o s i t i o n e f f e c t and m a t e r n a l  effects.  the  54.  MATERIALS AND  M u t a t i o n s and  METHODS  Chromosome R e a r r a n g e m e n t s :  A d e s c r i p t i o n of mutations used i n T a b l e 1. utilized  The  in this  v a r i o u s i n v e r s i o n s and  special  F u r t h e r d e t a i l s o f t h e s e chromosomes may  General Mating  of  x 95 mm  cornmeal,  be  shell vial  female  and  two m a l e s m a t e d i n a  c o n t a i n i n g s t a n d a r d medium composed  s u g a r , y e a s t and  agar w i t h p r o p i o n i c  p a r e n t s of the d e s i r e d genotype  F o r most  3 and  The  the temperature  All  e v e r y day)  studies.  were c o u n t e d  and  An  and  a t 25°C f o r t h e  classified  F o l l o w i n g the  every second according to  v i a l s w e r e s c o r e d t o e x t i n c t i o n and  period  suc-  development, w i t h the e x c e p t i o n of  sensitivity  e c l o s i o n , a l l progeny  experiments,  separately for  e x p e r i m e n t s were c o n d u c t e d  d u r a t i o n o f e g g - l a y i n g and  phos-  3 day p e r i o d s  t h e o f f s p r i n g o f each f e m a l e were m o n i t o r e d interval.  and  were t r a n s f e r r e d t h r o u g h  c e s s i v e egg l a y i n g i n t e r v a l s o f 4-,  studies,  from  Procedures:  p h o r i c a c i d added as mold i n h i b i t o r s .  each  obtained  2.  (1968).  C r o s s e s i n v o l v e d one 25 mm  chromosomes  a r e d e p i c t e d i n F i g u r e s 1 and  i n the experiments  L i n d s l e y and G r e l l  study i s provided  observed  day  initial ( i n some  phenotype. f o r a short  thereafter. important d e f i n i t i o n  i n t e r p r e t a t i o n of the term  i n t h e s e s t u d i e s has been t h e  " s u r v i v i n g progeny."  For the  pur-  55.  TABLE 1  MUTATIONS USED  Symbol  Name  Map Position  Phenotype  yellow  0.0  body  ac  achaete  0.0  hairs  missing  Hw  Hairy-winged  0.0  extra  bristles  sc  scute  0.0  bristles  pn  prune  0.8  eyes p u r p l e - b r o w n  white-apricot  1-5  eyes  y  a w cv sn v m f B car mal bb  yellow  missing  orange  crossveinless  13-7  crossveins  missing  singed  21 .0  bristles  vermilion  33-0  eyes  miniature  36.1  wings  forked  56.7  bristles  Bar  57-0  eyes narrow  carnation  62.5  eyes dark ruby  maroonlike  64.8  eyes  bobbed  70.0  bristles  twisted  scarlet small forked  purple short,  thin  56.  FIGURE  Diagramatic  1  representation of  the  s c u t e i n v e r s i o n chromosomes.  (C - c e n t r o m e r e , NO The  heterochromatic  matin  i s n a r r o w and  - nucleolus  organizer)  r e g i o n s a r e o p e n and  wide w h i l e  closed.  euchro-  57-  type  •  -H-r—  + +  NO  .L8 SC  + +  sc  sc  S1  •  NO  + + w sc  su-f  -+4  y  +•  NO  y sc  SC  su -f  •H  8  V2  su-f  NO  ySC  +  sc  NO  su-f  yscw  wild  su-r  su-f  w  + + + scNO  +-+  f  w -4-  •  NO  •  58.  FIGURE 2  D e s c r i p t i o n and s o u r c e o f Special  Chromosomes.  59.  Chromosome  Abbreviation  In(l  sc +S y B  In(l  sc  In(l  sc  In(l In(l In(l In(l In(l  sc  S 1  j  49 B f v  +dl  S 1  O  m  5  m  sc  3 1 d  8  dm B  bb~ f v c v  8  sc +  D.G. H o l m  s c - FM6  D.G. H o l m  s c f v cv  J.B. S p o f f o r d  In(l In(l  sc  In(l  sc  S 1 L  sc  8 R  +S B w  In(l  sc  S 1 L  sc  8 R  +S w  In(l  sc  In(l  sc  8  s c + d l 49 V2 sc  D.G. H o l m  4  8  8  49 y B f v -  sc +dl V2 sc  8  4  Bowling Green  sc  D.G. H o l m  Base  D.G. H o l m  a  asc  D.G. H o l m  49 B f v  vinscy  D.G. H o l m  S 1 L L8R  Generated  Ybb"  J.D. P r o c u n i e r  Dp ( l ; f ) 1187  Dp 1187  J.D. P r o c u n i e r  Dp ( l ; f ) 1337  Dp 1337  J.D. P r o c u n i e r  Dp ( l ; f ) 856  Dp 856 .  J.D. P r o c u n i e r  Df  y  Bowling Green Bowling Green  8  FM6 y  D.G. H o l m  Q  sc  8  J.B. S p o f f o r d  o  sn-  T  sc  49  +dl  sc  3  T O  sc  S 1  T O  O  sn-  sc  sc  +S y B  S 1  Source  sc  S 1 L  S  1  L  8 R  sc  L  +dl 8  R  (Y) bb"  Df  (1) bb -452  Df  ( 1 ) bb 2  y  su-w  bb  1  l  "  3  Y - YV  1  bb  452 2  r  l  "  J.D. P r o c u n i e r 3  J.D.  Procunier  X-Y  D.G. H o l m  C ( l ) RM y w  C(1)RM y w  D.G. H o l m  C ( l ) RM y v p n  C(1)RM y v p n  La J o l l a  2  a  w  r  a  a  s  60.  poses o f t h i s r e s e a r c h , an i n d i v i d u a l f l y w i t h f r e e o f l e g and wing p a r t s i s c o n s i d e r e d a s u r v i v o r .  mobility  Often during  t h e s e s t u d i e s , e x t r e m e l y f e e b l e f l i e s were o b s e r v e d m i r e d i n t h e medium.  As these i n d i v i d u a l s l a c k e d f r e e m o b i l i t y ,  they  h a v e n o t b e e n i n c l u d e d i n t h e r e s u l t s a n d t h i s e x c l u s i o n may s l i g h t l y bias the data. prominent  When t h e s e weak i n d i v i d u a l s w e r e a  f e a t u r e o f an experiment,  mate t h e i r f r e q u e n c y a n d p h e n o t y p e .  a n e f f o r t was made t o e s t i I n v a r i a b l y i t was f o u n d  t h a t t h e v a s t m a j o r i t y o f t h e s e i n v a l i d f l i e s were o f t h e scute X/0 genotype.  N e g l e c t i n g t h e s e i n d i v i d u a l s may  slightly  p r e j u d i c e the data but a l l values are thus conservative i n d i cations of v i a b i l i t y .  I t s h o u l d be p o i n t e d o u t t h a t i n no  c a s e d i d t h e s e d e a d a d u l t s r e p r e s e n t more t h a n 1$ o f t h e t o t a l progeny i n s p e c t e d . I n a number o f t h e e x p e r i m e n t s  r e p o r t e d , i t has been  n e c e s s a r y t o v a r y t h e r e s e a r c h t e c h n i q u e s from t h e p r e c e d i n g protocol.  Specific  changes a r e n o t e d a t t h e s t a r t o f each  c h a p t e r a l o n g w i t h an e x p l a n a t i o n f o r t h e d e v i a t i o n . line  An out-  o f s p e c i f i c mating p r o t o c o l s i s also provided w i t h  each  chapter. For the purposes ity  o f t h i s entire manuscript, the v i a b i l -  o f t h e s c u t e X/0 i n d i v i d u a l s w i l l be e x p r e s s e d a s a s e x  ratio.  T h i s number i s d e r i v e d b y d i v i d i n g t h e number o f m a l e  p r o g e n y b y t h e number o f f e m a l e p r o g e n y . o f 1.00  Thus, a sex r a t i o  r e p r e s e n t s an e q u a l f r e q u e n c y o f male and female  geny w h i l e a s e x r a t i o  o f 0.05  indicates a ratio  pro-  o f one m a l e  61.  to twenty females.  I n the heterozygote experiments, i t i s  n e c e s s a r y t o compare t h e number o f X/0 m a l e s , w i t h t h e a v e r a g e r e c o v e r y o f one f e m a l e g e n o t y p e .  The c o n t r o l s i t u a t i o n s s u g -  g e s t t h a t t h i s mechanism does n o t i n f l u e n c e t h e r e s u l t s t o a s i g n i f i c a n t extent.  I n these experiments, the comparison of  v i a b i l i t i e s w i t h i n an experiment  a r e more v a l i d t h a n compar-  i s o n s between s t u d i e s as i t i s apparent i n f l u e n c e t h e X/0  viability.  t h a t many f a c t o r s may  62.  RESULTS  - Chapter 1 P a r e n t a l Source E f f e c t :  I.  P a t e r n a l l y Derived X  I n t h e f i r s t p a r t o f t h i s s t u d y , m a l e f l i e s c a r r y i n g one of t h e scute  i n v e r s i o n X h r o m o s o m e s a n d a m a r k e d Y-chromosome _ c  w e r e m a t e d t o compound-X f e m a l e s l a c k i n g a f r e e Y.  The r e -  s u l t i n g p r o g e n y were compound-X/Y f e m a l e s a n d s c u t e X/0 m a l e s ( F i g u r e 3)'  The c o n t r o l , w h i c h was r u n s i m u l t a n e o u s l y ,  dif-  f e r e d only .in that t h e p a r e n t a l female c a r r i e d a f r e e Y-chromosome.  The d i f f e r e n c e s i n v i a b i l i t y i n t h i s e x p e r i m e n t a r e  presumably a r e s u l t o f t h e presence o r absence o f t h e Y-chromosome i n m a l e p r o g e n y . The r e s u l t s o f t h i s s e c t i o n a r e p r e s e n t e d will  be d e s i g n a t e d  "thepaternal effect."  i n Table  The most  striking  observation i s the l e t h a l i t y associated with the scute condition. to nal  Normally,  X/0 m a l e s a r e p h e n o t y p i c a l l y  t h e i r X/Y c o u n t e r p a r t s e f f e c t experiments,  except f o r s t e r i l i t y .  2 and  X/0  identical  I n the pater-  X/0 m a l e s e x h i b i t a p r o n o u n c e d  decrease  i n v i a b i l i t y a s c o m p a r e d t o t h e i r X/Y c o n t r o l s . The f i r s t  s c u t e i n v e r s i o n s t u d i e d was s c u t e - 8 , a n i n v e r -  s i o n w i t h break p o i n t s i n t h e heterochromatin  proximal  to the  n u c l e o l u s o r g a n i z e r and d i s t a l t o t h e s c u t e l o c u s i n t h e euchromatin.  The s c u t e - 8 X/0 i n d i v i d u a l s showed a t e n - f o l d  r e d u c t i o n i n v i a b i l i t y a s c o m p a r e d t o X/Y c o n t r o l s .  There  63-  FIGURE 3  M a t i n g scheme f o r generating  s c u t e X/0 m a l e s w i t h  d i f f e r e n t parental o r i g i n s of the X-chromosome.  64.  Paternal  sc /Y  Inheritance  ®  x  C(DRM/0  1 C(1)RM/  Y  sc / o x  + sc / X-Y x  A  sc /sc x  x  Maternal  ®  x-y/o  Inheritance  65. TABLE 2  Paternally  d e r i v e d X-chromosome: CONTROL Female  8  sc  sc  8  8  sc sc  8  sc  sc  S 1  sc  1  SI  sc  sc  S 1  SI  sc sc sc s  c  L8 L8  L8  sc sc  +  V 2  4  EXPERIMENT  Male  Sex Ratio  Female  Male  Sex Rati<  ^  1138  1173  1.03  2413  193  0.08  + dl49  1587  1682  1.06  2290  0.12  981  962  O.98  3647  275 0  1086  998  0.92  836  26  0.03  739  790  1.07  1681  223  0.13  734  682  0.93  1431  106  0.07  626  616  O.98  1340  54  0.04  1048  966  O.92  3812  198  0.05  617  551  0.89  2192  0  0.00  834-  711  -0.85  2608  0  0 .00  1072  0.96  1317  54  0 .04  672  0.79  2509  77  0.03  84-9  0.84  1984  81  0  O.72  2131  743  673 802  1.08  2371  671  0.26  1236  1393  1964  929  0.87  649  664-  1.13 1.02  791  0-97  su-f  SI  sc  lethality.  +  CV V f (FM6)  8  S c u t e X/0  ym +S +S y  B yB  6lk  + dl49 y  3  sn^  846  1010  m f3  1116  6a  94-1  815  0  0.00  .04  0.00  66.  were two p a r t i c u l a r scute-8 chromosomes t h a t v a r i e d g r e a t l y from t h i s o b s e r v a t i o n . The i n v e r s i o n scute-8 f v c v was i d e n t i f i e d as a bobbed l e t h a l i n numerous e x p e r i m e n t s o f t h i s paper.  T h i s chromo-  some produces no v i a b i l i t y i n c o m b i n a t i o n w i t h Ybb", 8R  Li,  sc  sc  -  bb , b b - 2 r l - 3 o r d u p l i c a t i o n s t h a t a r e bb .  Recom-  b i n a n t s o f t h i s chromosome c a r r y i n g t h e l e f t end have a l l been shown t o be s i m i l a r l y l e t h a l .  One cannot expect t o ob-  s e r v e s t a n d a r d s c u t e X/0 l e t h a l i t y i f t h e X-chromosome i s c a r r y i n g an a d d i t i o n a l Y s u p p r e s s e d  lethal.  The FM6-chromosome i s a s t a n d a r d , m u l t i p l y broken X-chromosome o f t h e scute-8 t y p e t h a t i s commonly used as a b a l a n c e r . One  o f t h e m u t a t i o n s c a r r i e d on t h i s chromosome (dm) i s asso-  c i a t e d w i t h reduced v i a b i l i t y i n X/0 males and s t e r i l i t y i n females.  The severe l e t h a l i t y observed w i t h FM6/0 males i s  l i k e l y a r e s u l t o f t h e combined s c u t e and d i m i n u t i v e marker effects. P h e n o t y p i c a l l y , t h e scute-8 X/0 males had a c h a r a c t e r i s t i c appearance.  The most o b v i o u s anomaly was t h e s t r o n g  achaete (ac) v a r i e g a t i o n which removed a c o n s i d e r a b l e p e r centage o f t h e m i c r o c h a e t a e from t h e e p i d e r m a l s u r f a c e s . T h i s conspicuous f e a t u r e i s d e a l t w i t h i n Chapter 8 o f t h i s text.  Other v a r i e g a t i n g systems observed were s c u t e ( s c ) ,  y e l l o w (v_) and H a i r y - w i n g (Hw) .  I n t h e s e s t u d i e s , i t has  been v e r y d i f f i c u l t t o s e p a r a t e t h e component e f f e c t s o f the  sc and Hw v a r i e g a t i o n as t h e s e m u t a t i o n s evoke q u i t e  67.  o p p o s i t e p h e n o t y p e s on t h e f l y . U p o n e c l o s i o n , t h e s e X/O t u r e and  flies  a p p e a r e d somewhat imma-  most e x h i b i t e d s p a s t i c c o n t r o l o f l e g s and  A f t e r a day  of maturing,  these  w i t h the o t h e r progeny but  i n d i v i d u a l s became  by  the  All  males r a t h e r than the  s u r v i v i n g X/0  levels.  are other  indicative  Throughout these  t l e s were a s s o c i a t e d w i t h t h e  s h o r t and  of reduced  t h e b r i s t l e s w e r e l o n g and  f l i e s b u t was  bristle i n the  e x p r e s s i o n and scute-8  X/0  i n s e v e r e l y bobbed  extremely  vast majority  presence of accessory  the p o s t e r i o r r e g i o n of the thorax.  type  of  most were  i n macrochaetae from the head, t h o r a x  frequent  of  studies.  The  scute-8  to  An-  i s the presence  o r more s c u t e l l a r b r i s t l e s and  A phenomenon p e c u l i a r t o t h e the  expression,  a r r a n g e m e n t was  males.  many  t h i c k as opposed  occurs  absent throughout these  f l i e s l a c k e d one deficient  This p e c u l i a r i t y  bris-  Although  s l e n d e r , i n d i c a t i v e o f the bobbed c o n d i t i o n .  abdominal e t c h i n g .  variable  ribosomal  e x c e s s bobbed  males.  o t h e r i n d i c a t i o n o f r e d u c e d rRNA c o n t e n t  The  as r e c e n t l y  examined f o r the  of the v a r i e g a t i n g phenotypes a f f e c t e d b r i s t l e when p r e s e n t ,  of  genotypes.  s t u d i e s , no s c u t e X/0  is  condition.  identified  m a l e s were c a r e f u l l y  p r e s e n c e o f bobbed b r i s t l e s , RNA  s c u t e X/0  f a c t t h a t the v a s t m a j o r i t y  i n d i v i d u a l s f o u n d dead i n the f o o d e c l o s e d X/0  competitive  t h i s developmental abnormality  a g e n e r a l phenomena a s s o c i a t e d w i t h t h e This i s i l l u s t r a t e d  wings.  and  inversions  abdomen. was  dorsocentral bristles These e x t r a  bristles  on  68.  had  a unique socket  and  dorsocentral sockets.  were n o t The  a l l . b o d y s u r f a c e s was  a s s o c i a t e d w i t h the  p o s i t i o n i n g of the macrochaetae  abnormal.  Often, b r i s t l e s appear to  r a n d o m l y d i s t r i b u t e d on t h e e p i d e r m i s  r a t h e r than  to  individuals.  the  s p e c i f i c p a t t e r n s of w i l d type  a l s o observed  regular on be  conforming It  was  t h a t c e r t a i n macrochaetae were e s p e c i a l l y  sen-  s i t i v e to p a t t e r n d i s t u r b a n c e s w h i l e others remained unaff e c t e d by t h e m u t a n t c o n d i t i o n . described i n a l a t e r chapter phenotypes as a g e n e r a l The  dealing with variegating b r i s t l e  p a t t e r n d i s t u r b a n c e s w e r e p a r t i c u l a r l y e v i d e n t when  individuals.  c h a e t a e p a t t e r n s and uals.  be  phenomenon.  observing the microchaetae t h e X/0  These d i f f e r e n c e s w i l l  on t h e  T h e r e was  s u r f a c e of the thorax  great d i v e r s i t y of the  e x p r e s s i o n i n the  s c u t e - 8 X/0  of micro-  individ-  M o s t commonly, t h e f l y e x h i b i t e d s m a l l b a l d p a t c h e s  t h e t h o r a x and  d i s c o n t i n u i t y of the l i n e a r b r i s t l e  Less extremely  a f f e c t e d i n d i v i d u a l s d i s p l a y e d near-normal  b r i s t l e number b u t  still  showed a b n o r m a l b r i s t l e  F u r t h e r i n v e s t i g a t i o n demonstrated t h a t the disturbances  series.  distribution.  microchaetae  e x t e n d e d t o t h e a b d o m i n a l s u r f a c e s where  b a l d i n g and p a t t e r n a b n o r m a l i t i e s w e r e o b s e r v e d . e g a t i o n of the b r i s t l e  loci  a p p e a r s t o be  problem i n v o l v i n g both  the b r i s t l e  a  on  The  both vari-  developmental  e x p r e s s i o n and  pattern  determination. The  s c u t e - 8 X/0  m a l e s were o b s e r v e d  than t h e i r female s i b s .  t o e c l o s e much l a t e r  T h i s d e v e l o p m e n t a l d e l a y was  striking  69.  and  consistent  X/0  males  majority cal  throughout these experiments. 2 - 4 -  eclosed  days a f t e r the  15-  o f i n d i v i d u a l s e c l o s i n g a f t e r day  length  a rather  o f d e v e l o p m e n t and  t i o n i n the  mutants.  scute-8  X/0  Often, late  the  males.  strong  A more  vast criti-  in  c o r r e l a t i o n "between  degree o f b r i s t l e  Those f l i e s  eclosing f l i e s  t h a t t h e y drop d i r e c t l y  i n t o the  are  rescued from the Generally,  f o o d and  these f l i e s  c l a s s of progeny.  These, d a t a a r e  developmental delay  The  next scute  some t h a t  euchromatically  available  the  proximal  contain  s i x scute-Si  the  affected  are unable to  i n the  affected  discussion  7scute-Si, a  chromo-  X-heterochromatin  to the scute  scute  locus  locus).  and  (i.e.  Four of  chromosomes a l s o c a r r y one  i n v e r s i o n s , e i t h e r I n ( l ) dl4-9  escape.  recorded.  most s e v e r e l y  included  i n Chapter  just proximal  i n v e r s i o n does not  severely  m i r e d i n d i v i d u a l s were  i n v e r s i o n s t u d i e d was  i s broken i n the  i n v a r i a b l y extreme  b r i s t l e p h e n o t y p e s were  represented  variega-  eclosing after  so  f o o d and  I n a number o f t h e s e e x p e r i m e n t s , t h e  stitial  the  i s provided  abnormally extended development time are  of the  the  7«  T h e r e a p p e a r s t o he  an  females with  assessment of t h i s developmental delay  Chapter  the  Generally,  o r I n ( l ) S.  the the  o f two I t has  o b s e r v e d p r e v i o u s l y t h a t m u l t i p l y b r o k e n chromosomes may deleterious properties associated ( R a f f e l and  Muller,  suggested f o r the  194-0).  first  This  scute-Si  w i t h the has  extra  a l s o been  interbeen have  breakpoints  specifically  i n v e r s i o n s t h a t were r e c o v -  70.  e r e d by t h e  Soviet  S i n i t s k a y a , 1931)i n the X/Y  group i n the  early t h i r t i e s  Evidence f o r t h i s  data displayed  i n T a b l e 2.  males c a r r y i n g a s c u t e - S i  (Muller  s u g g e s t i o n may  of the  H o w e v e r , t h i s may  with  a t e d w i t h the studied  scute-Si  control  i n t e r p r e t e d a s an  X/0  i s a dramatic l e t h a l i t y  someexper-  effect  absent.  v i d u a l s were n o t t h a t the  Severely  scute-Si  The  o t h e r two  with  suggests t h a t the  scute-8 f v cv.  produce  observed viable X-chro-  a Ybb-chromosome. severe  situation previously  lethality  condition i s associated  with  and  locus.  a great  deal  defor  lethality  scute l e t h a l i t y  as  complete i n v i a b i l i t y .  Thus, experiments i n v o l v i n g t h e s e s c u t e - S i provided  described  I t i s d i f f i c u l t to p a r t i t i o n the  i n t o components o f bobbed l e t h a l i t y  scute  I t was  indi-  w i t h ' t h e s e chromosomes i s a r e s u l t o f a b o b b e d  f i c i e n c y analogous to the  have not  X/0  b o b b e d f l i e s w e r e r e c o v e r e d when t h e s e  evidence strongly  bb~  crosses.  the  scute-Si  e i t h e r rDNA d e f i c i e n t Y o r  chromosomes w e r e a s s o c i a t e d  associated  examples of  i n v e r s i o n , I n ( l ) d l ^ 9 , and  with  mutants  i n v i a b i l i t y when  + dl49-chromosomes d i d not  p r o g e n y when a s s o c i a t e d mosomes.  reduction  g e n e r a t e d f r o m any  scute-Si  associ-  c o n d i t i o n . . Four of the  showed a t w e n t y - f o l d  chromosomes c a r r i e d t h e  the  normal  i n v e r t e d X-chromosome a r e  a l s o be  scute-8, there  Y-chromosome was  the  found  scute i n v e r s i o n i t s e l f .  As  This  be  I t appears t h a t the  what l e s s v i a b l e t h a n t h e i r f e m a l e s i b s i n the iments.  and  +  of information  dl49-chromosomes relating  to  71.  Phenotypically,  scute-Si d i f f e r s  I n X/Y  males, the  strong  scute phenotype w h i l e  s c u t e - S i genotype c o n f e r s  rochaetae missing. acteristic ated  in scute-8,  Scute-Si  .  only r a r e l y are  mac^ char-  be  f o r a l l of the  identified  on  different  the b a s i s of the  t r a i t s when o t h e r m a r k e r s f a i l . m a l e s do n a t  s c u t e gene ( R a f f e l and  been p a r t i c u l a r l y u s e f u l i n  s t u d i e s as h e t e r o z y g o t e s  other  a moderately  r e d u c t i o n i n abdominal macrochaetes t h a t i s a s s o c i -  T h i s f e a t u r e has  s i o n s can  scute-8.  individuals also exhibit a  w i t h the v a r i e g a t i o n of the  194-0)  somewhat f r o m  e x h i b i t a sever  I n t h e X/Y  Muller,  these  scute  abdominal  inver-  bristle  condition, scute-Si  a c h a e t e p h e n o t y p e o r any  v a r i e g a t i o n f e a t u r e s t h a t were e v i d e n t  i n the  of  the  scute-8  flies. In scute-Si X/0 c h a n g e was  the  epithelial  surfaces.  m a l e s , t h e most s t r i k i n g  enormous r e d u c t i o n o f m a o r o c h a e t a e f r o m a l l The  n o r m a l i n a p p e a r a n c e and viduals, . ber,  as  was  a l t e r e d but  not  the  d i d not  s e v e r l y as  when p r e s e n t ,  appear bobbed.  were  I n most  of the  seen i n s c u t e - 8 .  Bristle  I t appears t h a t the major  scute-8  i n v e r s i o n a f f e c t s the  a c h a e t e gene t o a g r e a t e r Developmentally,  e c l o s i n g on t h e  was  scute  expression  of  extent.  s c u t e - S i X/0  average, 2 - 3  num-  phenotypic  s c u t e - S i i n v e r s i o n i s v a r i e g a t i o n of the  the  indi-  pattern  remained d i s t i n g u i s h a b l e i n l i n e s which  case i n s c u t e - 8 .  gene w h i l e the  major b r i s t l e s ,  t h e m i c r o c h a e t a e were s i g n i f i c a n t l y r e d u c e d i n  but not  effect  phenotypic  males are  extremely  days l a t e r than female  slow, sibs.  72.  As w i t h s c u t e - 8 , t h e s e v e r i t y o f phenotype i s d i r e c t l y to  the d u r a t i o n of development.  i n Chapter  7.  The  scute-Si  severely incapacitated X/0 of  p r o g e n y and  These s t u d i e s are r e p o r t e d  f l i e s w e r e a l s o among t h e most  i m m e d i a t e l y a f t e r e c l o s i o n as o f t e n  m a l e s c o u l d he r e t r i e v e d t h e s e dead X/0  related  from the food.  individuals  The  o f t e n approached  frequency  1$  of the  t h i s r e p r e s e n t e d t h e most common o b s e r v a t i o n o f  trapped males.  I t appears  t h a t X/0  males c a r r y i n g a  scute-Si  X-chromosome a r e a t an e x t r e m e s e l e c t i v e d i s a d v a n t a g e ing  eclosion.  we  had  third  scute-L8 of  None o f t h e s c u t e - L 8  i n t e r s t i t i a l i n v e r s i o n s , t h u s any  c a n be a t t r i b u t e d  One  somes c a r r i e d a v e r y s e v e r e a l l e l e  observed  infertility.  The  difficulty  e f f e c t s of the  of forked ( f _ _ _ )  chromowhich  viability  i n maintaining this  o f X/0  lethality  of the scute-L8  has been p r e v i o u s l y a s s o c i a t e d w i t h reduced  which  chromosomes  to marker e f f e c t s or d i r e c t  scute i n v e r s i o n rearrangement.  and  days.  s c u t e i n v e r s i o n s t u d i e d was  t h r e e examples.  carried  follow-  As w i t h s c u t e - 8 , t h e s e weak f l i e s m a t u r e d  became f u l l y c o m p e t e n t a f t e r 1 - 2 The  total  the complete  inviability  males suggest  l e m s a r e due  to the marker e f f e c t of the f o r k e d  and  stock  t h a t the  and prob-  allele.  36a R e c o m b i n a n t chromosomes c a r r y i n g t h e f.  allele  J  t h e same l e t h a l i t y  profile.  g u i s h e d f r o m t h e bb~  T h i s m a r k e r e f f e c t was  homologue.  distin-  e f f e c t by d e m o n s t r a t i n g t h e v i a b i l i t y 36a  i n d i v i d u a l s c a r r y i n g both the scute-L8 f a bb~  demonstrated  J  chromosome  and  of  73-  T h e r e was  a s e v e r e r e d u c t i o n i n v i a b i l i t y when t h e  s c u t e - L 8 m a l e s l a c k e d a Y-chromosome.  The  lethality  observed  f o l l o w e d a s i m i l a r p a t t e r n to t h a t witnessed i n the p r e v i o u s experiments w i t h s c u t e - S i , although fewer covered.  Moreover,  s u r v i v o r s were r e -  t h e c o n t r o l m a l e s showed a m a r k e d  reduc-  t i o n i n v a r i a b i l i t y e v e n when a s s o c i a t e d w i t h a Y-chromosome. P h e n o t y p i c a l l y , scute-L8 mimics observed i n scute-Si vere.  X/Y  the mutant  conditions  e x c e p t t h a t t h e e x p r e s s i o n i s more s e -  m a l e s c a r r y i n g s c u t e - L 8 show a s t r o n g s c u t e p h e n o -  t y p e t h a t i s m a n i f e s t e d by s e v e r e r e d u c t i o n o f  macrochaetae  e x p r e s s i o n e v i d e n c e d e s p e c i a l l y by t h e s c u t e l l a r (see Chapter  8).  I n an X/0  almost a n n i h i l a t e d .  individual,  the macrochaetae  Only r a r e l y are the l a r g e b r i s t l e s  s e r v e d on t h e h e a d and t h o r a x .  The  abdomen i s d e v o i d o f m a c r o c h a e t a e for  bristles  ob-  d o r s a l s u r f a c e of the  and  i s largely bald  sparge, d i s o r g a n i z e d microchaetae.  The  except  ventral surface  e x h i b i t s a s i m i l a r b u t more s e v e r e p h e n o t y p e . i s t h e s i n g l e , most c h a r a c t e r i s t i c  are  T h i s phenotype  f e a t u r e of a l l the  scute-L8 stocks studied. The  microchaetae  t i a l l y normal  i n X/X  and X/Y  scute-L8 f l i e s  are  essen-  e x c e p t f o r a s i g n i f i c a n t r e d u c t i o n on b o t h  dominal  surfaces.  achaete  l o c u s but to a l e s s e r extent than e i t h e r scute-8 or  scute-Si.  The  X/0  ab-  m a l e s show v a r i e g a t i o n f o r t h e  I n many c a s e s t h e m i c r o c h a e t a e  t h e w i l d t y p e c o n d i t i o n w h i c h was not  seen i n s c u t e - 8 (see Chapter  rarely 8).  counts  overlapped  seen i n s c u t e - S i  and  74.  Scute-L8  demonstrated  t h e same d e v e l o p m e n t a l  observed i n the p r e v i o u s s t u d i e s .  The  m a j o r i t y of males are  recovered f a r l a t e r than the s i b females. e c l o s i n g a f t e r an e x t e n d e d p e r i o d phenotypes. the  Occasionally, X/0  Again, those  be a r e s u l t  m a l e s were f o u n d t r a p p e d i n  of the e a r l i e r l e t h a l i t y  s c u t e - L 8 a s much f e w e r  flies  showed t h e most e x t r e m e  f o o d but n o t as f r e q u e n t l y as i n the s c u t e - S i  T h i s may  profile"as  experiments.  observed i n  scute-L8 larvae reach pupation ( i n  preparation). It  i s apparent that  s c u t e - L 8 i s t h e most e x t r e m e o f t h e  scute v a r i e g a t i n g mutants. chaetae of  The  s t r i k i n g absence o f macro-  on t h e e p i d e r m a l s u r f a c e s i s a c h a r a c t e r i s t i c  t h i s chromosome.  Although s l i g h t l y  l e s s v i a b l e than i t s  other scute c o u n t e r p a r t s , scute-L8 e x h i b i t s the of  feature  complement  d e v e l o p m e n t a l phenomena t h a t c h a r a c t e r i z e t h e s c u t e  sion  inver-  effect. The  f o u r t h chromosome s t u d i e d was  scute-V2, which  p e c u l i a r chromosome a s i t h a s a p r o x i m a l b r e a k w i t h i n  is a the  n u c l e o l u s o r g a n i z e r r e g i o n as s u g g e s t e d by g e n e t i c e v i d e n c e reported to  i n Chapter  3-  The  euchromatic break  i s very  similar  t h a t r e p o r t e d f o r the scute-8 i n v e r s i o n w i t h the scute  gene c o n t a i n e d w i t h i n t h e r e a r r a n g e m e n t . s i o n appears  The  scute-V2  inver-  t o be v e r y s i m i l a r t o t h e p r e v i o u s t h r e e m u t a n t s  w i t h one m a j o r e x c e p t i o n .  Recent  studies indicate that  both  e n d s o f t h e s c u t e - V 2 chromosome c o n t a i n s u f f i c i e n t r i b o s o m a l DNA  to survive independently.  This subject w i l l  be  dealt  75.  w i t h i n some l e n g t h i n t h e . d i s c u s s i o n . I n t h e X/0 reduced.  s i t u a t i o n , the v i a b i l i t y  This l e t h a l i t y  of scute-V2  i s greatly  i s n o t as s e v e r e as o b s e r v e d w i t h  t h e t h r e e p r e v i o u s s c u t e i n v e r s i o n s and t h e  developmental  phenomena a s s o c i a t e d w i t h t h e m o r t a l i t y do n o t a p p e a r as extreme.  A developmental  a t i o n o f t h e s c u t e - V 2 X/0  delay i s observed  X/0  i s no  flies  late.  statistical  m a l e s b u t t h i s p e r i o d i s much r e -  s c u t e - V 2 X/0  i t i v e w i t h t h e i r female the food.  or scute-L8.  d i f f e r e n c e between the phenotypes  e c l o s i n g e a r l y i n the experiment  Moreover,  be  i n the matur-  d u c e d a s c o m p a r e d t o t h e same p e r i o d i n s c u t e - S i There  to  males appear  and t h o s e  of  eclosing  t o be v e r y compet-  s i b s and a r e r a r e l y f o u n d t r a p p e d i n  These f a c t o r s a l l s u g g e s t t h a t the scute-V2  s i o n i s somewhat d i f f e r e n t t h a n t h e t h r e e p r e v i o u s l y  inver-  studied  rearrangements. Phenotypically,  s c u t e - V 2 most c l o s e l y r e s e m b l e s  as t h e most p r e v a l e n t mutant c o n d i t i o n v i s i b l e X/Y  males c a r r y i n g scute-V2  o t h e r macrochaetae  i s achaete.  show o b v i o u s p a t t e r n s o f v a r i e g a -  t i o n a s s o c i a t e d w i t h the microchaetae. and  scute-8  The  scutellar  bristles  remain r e l a t i v e l y u n a f f e c t e d although  a c c e s s o r y b r i s t l e s w e r e n o t a n uncommon o c c u r r e n c e on t h e t e r i o r thorax. X/Y  The m o s t s t r i k i n g v a r i e g a t i o n p a t t e r n i n t h e  i n d i v i d u a l s was  ment.  There  exhibited  i n the abdominal  bristle  were s t a n d a r d numbers o f macrochaetae  on b o t h d o r s a l and v e n t r a l g r e a t l y reduced.  pos-  arrange-  present  s u r f a c e s but the microchaetae  T h i s p h e n o t y p e was  very characteristic  were in  76.  all  of the s t u d i e s i n v o l v i n g the scute-V2 The  last  o f t h e s t a n d a r d s c u t e i n v e r s i o n chromosomes t o scute-4.  be s t u d i e d was inversions,  chromosome.  I n comparison w i t h the p r e v i o u s f o u r  s c u t e - 4 i s a t y p i c a l i n t h a t i t does n o t  the n u c l e o l u s o r g a n i z e r region.  The  include  euchromatic breakpoint  h a s b e e n r e p o r t e d t o be v e r y s i m i l a r t o t h a t s e e n i n b o t h s c u t e - S i and  scute-L8.  The  h e t e r o c h r o m a t i c b r e a k p o i n t , how-  ever, is.s i t u a t e d i n the d i s t a l - X heterochromatin r a t h e r t h e p r o x i m a l r e g i o n as i n t h e o t h e r s c u t e i n v e r s i o n s . s c u t e - 4 m a l e c a r r y i n g a Y-chromosome a p p e a r s t o be c o m p e t i t i v e w i t h h i s female  condition,  viability somes.  as t h e i r  There  scute-4/0  The  fully  s i b s , which i s c o n t r a d i c t o r y to  the o b s e r v a t i o n s from the o t h e r comparable t h e X/0  than  inversions.  s c u t e - 4 m a l e s a p p e a r t o be o f  In  similar  s i b f e m a l e s o r c o n t r o l m a l e s w i t h Y-chromo-  i s no d e v e l o p m e n t a l d e l a y o b s e r v e d f o r t h e  m a l e s and t h e y w e r e r a r e l y ,  i f ever found mired i n .  the food. Phenotypically, scute-Si,  scute-4 o b v i o u s l y belongs w i t h the  s c u t e - L 8 group.  The  major v a r i e g a t i n g system  p e a r s t o be t h e s c u t e l o c u s a s t h e m a c r o c h a e t a e q u e n t l y mutant.  I n t h e X/Y  situation,  a r e most  scute-4 males  apfre-  greatly  o v e r l a p w i l d type w i t h r e s p e c t t o t h e i r macrochaetae  pheno-  scute-4 males  produce  type.  F o r e x a m p l e , 60%  4 scutellar bristles.  of a l lnormal  T h i s i s a much l e s s s e v e r e s c u t e p h e n o -  type than t h a t seen i n both s c u t e - S i  and s c u t e - L 8 .  The m i c r o c h a e t a e a r e l a r g e l y u n a f f e c t e d by t h e  scute-4  77-  inversion.  T y p i c a l l y , the t h o r a c i c microchaetae count approx-  imates t h a t observed i n Oregon R c o n t r o l s t o c k s a l t h o u g h t e r n d i s t r i b u t i o n i n the irregular.  pat-  s c u t e - 4 i n d i v i d u a l s i s much more  There are d i s t i n c t d i f f e r e n c e s e v i d e n t  abdominal s u r f a c e s , however.  on  I n scute-4, t h e r e are  the  signifi-  c a n t r e d u c t i o n s i n b o t h m a c r o c h a e t a e and m i c r o c h a e t a e on s u r f a c e s and tion.  The  this i s particularly  e v i d e n t i n t h e X/0  exhibit a lethality  s t a t e w h i l e s h o w i n g an o b v i o u s  m u t a n t shows t h e l e a s t o v e r a l l p h e n o t y p i c  and X/0  c o n t r o l f o r these  scute-4  c h a n g e as a  s t u d i e s was  homozygous w i t h a s t a n d a r d  C o n t r o l s were r u n on i d e n t i c a l f o o d and the experimental  be  result  controls i n  conditions.  w i l d type  stock maintained  The  o v e r l a p s the w i l d type  X/0  I t i s not  appears to  d i v o r c e d f r o m an e f f e c t on t h e a c h a e t e g e n e .  o f i t s r e a r r a n g e m e n t and  i n the  scute phenotype.  a s s o c i a t e d -with a d e v e l o p m e n t a l d e l a y and  The  condi-  scute-4- i n v e r s i o n i s c h a r a c t e r i z e d as p e c u l i a r  t o t h i s s t u d y as i t does not  b o t h X/Y  both  crosses.  The  an O r e g o n R  Y-chromosome.  simultaneously  with  Oregon R s t r a i n d i d not  show  a m a l e - s p e c i f i c d e v e l o p m e n t a l d e l a y and  bristle  patterns  were n o t  In a l l  experiments,  X/0  a l t e r e d i n t h e X/0  condition.  O r e g o n R m a l e s a p p e a r e d t o be c o m p e t i t i v e w i t h  s i b s and  t h e y were e q u a l l y as  viable.  female  78.  P a r e n t a l Source E f f e c t :  The  II.  s e c o n d method o f p r o d u c i n g  females c a r r y i n g scute  X/0  3).  The  X-Y  males which  control  m a l e s t h a t c a r r y a f r e e Y-chromosome.  p o s e o f t h i s e x e r c i s e was  to determine i f the  a n o m a l i e s a s s o c i a t e d w i t h X/0  scute  X  males i n v o l v e s mating  chromosomes t o a t t a c h e d  l a c k f r e e Y-chromosomes ( s e e F i g u r e i n v o l v e s X•Y  Maternally Derived  situation The  pur-  developmental  i n v e r s i o n m a l e s were  sub-  j e c t to p a r e n t a l m o d i f i c a t i o n . The vided  r e s u l t s of the m a t e r n a l e f f e c t experiments are  i n T a b l e 3 and  maternally is  viability  d e r i v e d X/0  comparisons of p a t e r n a l l y  males are presented  i n Figure  immediately apparent t h a t the v i a b i l i t y  i n d i v i d u a l i s c o n d i t i o n a l and  of the  a p p e a r s t o be  t h e p a r e n t a l s o u r c e o f t h e X-chromosome.  For  was  e n h a n c e d when t h e  i n v e r t e d X-chromosome was  f i v e and  t e n - f o l d with- the  4.  It  scute  X/0  a l l but  scute, i n v e r s i o n s s t u d i e d i n t h e s e e x p e r i m e n t s ,  female.  and  dependent upon  the  from the  pro-  one  of  viability  inherited  I n most s t r a i n s , t h i s d i f f e r e n c e was scute-4 i n v e r s i o n being  between  the  only  exception. The  maternal e f f e c t a s s o c i a t e d w i t h the  somes was  striking.  The  s c u t e - 8 chromo-  d i f f e r e n c e b e t w e e n m a t e r n a l and  t e r n a l i n h e r i t a n c e was  t e n - f o l d and  maternally  m a l e s were c o m p a r a b l y v i a b l e t o the  d e r i v e d X/0  often higher.  pa-  male progeny recovered  from the  same c r o s s .  showed t h i s m a t e r n a l l y  determined increase.  Often,  the fe-  Almost a l l s t r a i n s T h i s i s i n marked  79.  TABLE 3  The S c u t e M a t e r n a l E f f e c t X /  sc / s c  X  x  X-Y/0  CONTROL Male  Sex Ratio  1017  1239  1637  2191  -  -  938  991  1.06  1173  1289  710  717 912  1  .01  1943  894  0.46  1982  0.42  Female  8 ^+  sc  sc  8  8  sc  8  + dl49 cv V f  sc s u - f SI sc ym sc  S 1  +S yB  sc  S 1  +S B  sc  S 1  sc sc  SI  L8  sc g c  L8  sc sc +  L8  V 2  4  + dl49 y  61 k  sn  3  m f3  939 658  688  Female  Male  Sex Rati)  1.22  1344  1572  1.17  1.34  1577  2019  1.28  -  0.97 1  .05  -  4716 1426  -  528.  -  1.10  0.37  -  -  -  -  -  -  -  -  -  -  -  -  367  339 360  0.92  780  226  0.29  0.87  607  201  0.33  -  -  412  6a  EXPERIMENT  -  -  -  -  1213  1456  1 .20  1302  1536  1.18  771  817 616  1.06  1021  1009  0.99  1.05  616  659  1.07  587  80.  c o n t r a s t t o t h e p r e v i o u s e x p e r i m e n t s where X/0 sented a low v i a b i l i t y Phenotypically,  class.  scute-8 females are l e s s mutant  scute-8 males w i t h r e s p e c t to macrochaetae f e m a l e s p r e d o m i n a n t l y o v e r l a p w i l d t y p e and major  males r e p r e -  b r i s t l e s missing.  expression.  These  only r a r e l y  are  Quite to the c o n t r a r y , scute-8 f e -  m a l e s show many more a c c e s s o r y b r i s t l e s on t h e thorax or scutellum.  than  The  microchaetae  posterior  expression i n scute-8  f e m a l e s i s somewhat more c o n s i s t e n t t h a n t h a t s e e n i n t h e  males.  P a t t e r n d i s r u p t i o n i s f r e q u e n t but b r i s t l e numbers o v e r l a p w i l d type i n the v a s t m a j o r i t y of The  phenotypes  o f t h e X/0  individuals.  m a l e s whose s c u t e X h a s  been  i n h e r i t e d f r o m t h e f e m a l e a r e l a r g e l y t h e same a s t h o s e  ob-  served i n the p a t e r n a l experiments.  excep-  There  i s one m a j o r  t i o n however, as t h e v e r y s e v e r e l y mutant i n d i v i d u a l s never observed t i o n o f X/0  i n the maternal experiments.  Thus, a p o p u l a -  m a l e s from t h e m a t e r n a l c r o s s e s has a  phenotypic p r o f i l e  are  to the g e n o t y p i c a l l y i d e n t i c a l  comparable individuals  r e c o v e r e d f r o m t h e p a t e r n a l c r o s s e s p r o v i d e d one n e g l e c t s t h e f l i e s w i t h a v e r y extended to ignore t h i s The  developmental period.  s i g n i f i c a n t group would  Unfortunately,  s e v e r e l y b i a s the  most o b v i o u s p h e n o t y p i c f e a t u r e o f t h e s e m a l e s was  a c h a e t e p a t t e r n on b o t h t h e t h o r a x and abdomen. mental  d e l a y was  g r e a t l y reduced  paternal experiments.  The  n a l e f f e c t s t u d i e s appear  X/0  The  from t h a t observed  males produced  study.  the  developi n the  i n these  t o be v e r y s t r o n g a t e c l o s i o n  materand  81.  FIGURE  X/0 parental  viability  4  associated  inheritance  with  of the scute  different X-chromosomes.  Paternally  derived  X  -  unlined  Maternally  derived  X  -  lined  82.  Sex 10  —i  ratio  20  30  40  50  60  1  1  1  1  1  70  80  l  I  90  100 110 120 130  I  i  i  8 , +  sc  117  12  8 sc + dl 49  2:  128  / / / / / / / I  13  su-f  sc  S1 sc  y m  z  46  42  S1  S 1  B+S  L8  sc  sc  sn  L 8  _V2  sc  sc  3  m  110  /////////////S71T7\  z  sc yB+S  sc  i  i  W2 37  /////// o  2.9  33  / / / / / / A 26 118  /////////////////////7-7-A ^  87 ^ j ^  ^99 97  107  83-  were n e v e r f o u n d t r a p p e d i n t h e f o o d . the  I t i s evident that  p a r e n t a l s o u r c e o f t h e m u t a n t chromosome h a s a p r o f o u n d  e f f e c t on a l l o f t h e d e v e l o p m e n t a l phenomena a s s o c i a t e d w i t h the  scute-8 The  the  chromosome.  second group  of maternal e f f e c t s studied  s c u t e - S i chromosome.  "fact"  that scute-Si  O r i g i n a l l i t e r a t u r e has c i t e d  he  circumvented.  d i s c o v e r y o f t h e c o n d i t i o n a l f e r t i l i t y was  as numerous n o n d i s j u n c t i o n a l s c u t e - S i one  These  i s not a permanent  f e a t u r e o f a l l s c u t e - S i f e m a l e s and may  in  fortuitous  f e m a l e s were r e c o v e r e d  of the p a t e r n a l e f f e c t experiments.  Some o f t h e s e  f e m a l e s were i m m e d i a t e l y m a t e d t o s t a n d a r d m a l e s t o  determine  f e r t i l i t y w h i l e the balance of these females remained inverted v i a l .  Three  f e m a l e s had d i e d , appeared  i n an  days l a t e r , t h e m a j o r i t y o f t h e mated  stranded i n the food.  The  remaining females  v e r y s t r o n g and were t h e n m a t e d t o s t a n d a r d m a l e s .  M o r e t h a n 50% to  the  females are v i a b l e hut i n f e r t i l e .  e x p e r i m e n t s show t h a t t h i s i n f e r t i l i t y  The  involved  of these females produced progeny  and  appeared  be t y p i c a l o f o t h e r homozygous s c u t e f e m a l e s t h a t  been s t u d i e d .  A p p a r e n t l y , the i n f e r t i l i t y  had  of scute-Si  females  c a n be l a r g e l y a v o i d e d i f t h e f e m a l e s a r e a l l o w e d t o m a t u r e in the  a dry environment f l y t o " c a t c h up"  f o r a few d a y s .  d e v e l o p m e n t a l l y a s w i t n e s s e d by  change i n motor a b i l i t y Phenotypically, s c u t e - S i males.  The  T h i s seemingly allows  b e t w e e n e c l o s i o n and day  scute-Si  3>  f e m a l e s a r e v e r y much  macrochaetae  p a t t e r n s are  the  like  inconsistent  84.  and many b r i s t l e s a r e m i s s i n g a l t o g e t h e r . o b s e r v e d on a l l e p i d e r m a l s u r f a c e s . are  typically  tern.  The  T h i s phenotype i s microchaetae  subnormal but not d r a s t i c a l l y a l t e r e d  D e v e l o p m e n t a l l y , homozygous s c u t e - S i  counts  i n pat-  f e m a l e s do  not  show a d e l a y a s c o m p a r e d t o w i l d t y p e s i b s e c l o s i n g i n t h e same  experiment. The  maternal effect  observed w i t h scute-Si  a b l e magnitude to t h a t seen i n s c u t e - 8 .  The  i s o f compar-  X/0  individuals  r e c e i v i n g t h e i n v e r t e d X f r o m t h e i r mother were e i g h t  times  as v i a b l e as t h e i r p a t e r n a l l y d e r i v e d c o u n t e r p a r t s (see F i g u r e 4 ) . - The  scute-Si  inversions carrying In(l) d l 4 9  an i n t e r s t i t i a l  i n v e r s i o n c a n n o t be r e c o v e r e d i n homozygous  f e m a l e s a s t h e y a p p e a r t o be b o b b e d The  as  deficiencies.  mutant appearance o f the s c u t e - S l / O males i n t h i s  experiment  i s very s i m i l a r to t h a t observed i n the  e f f e c t experiments.  The  s c u t e l l a r b r i s t l e s and  paternal  o t h e r macro-  chaetae are profoundly a f f e c t e d w h i l e the b r i s t l e s  of micro-  c h a e t a e d e r i v a t i o n show some i n c r e a s e i n v a r i e g a t i o n . w i t h s c u t e - S i , t h e r e a r e no observed to eclose very l a t e T h i s produces  s e v e r e l y mutant i n the maternal  experiments.  i n the p a t e r n a l experiments.  opmentally, the scute-Sl/O males are s t i l l but developmental d e r i v e d X/0  individuals  a p o p u l a t i o n w i t h much l e s s v a r i a t i o n o f  number t h a n i s o b s e r v e d  Again  bristle Devel-  somewhat d e l a y e d  time i s f a r s h o r t e r than w i t h the  paternally  males.  These e x p e r i m e n t s i n d i c a t e t h a t p r e v i o u s s u g g e s t i o n s o f  85.  s c u t e - S i female i n f e r t i l i t y arose as a r e s u l t  of the matings  of  matured. s c u t e - S i  immature f e m a l e s .  Crosses i n v o l v i n g f u l l y  females i n d i c a t e that scute-Si  i s not a t y p i c a l of the scute  i n v e r s i o n s w i t h r e s p e c t t o t h e m a t e r n a l e f f e c t and d e v e l o p mental  phenomena.  The s c u t e - L 8 chromosome p r e s e n t e d a p r o b l e m that encountered w i t h s c u t e - S i .  s i m i l a r to  I t was f o u n d t h a t t h e homo-  z y g o u s s c u t e - L 8 f e m a l e s w e r e somewhat i n v i a b l e and f r e q u e n t l y 36a sterile.  The i n v e r s i o n c o n t a i n i n g f  J  c o u l d n o t be r e c o v -  e r e d i n a homozygous s c u t e - L 8 f e m a l e p r e s u m a b l y of  the severe e f f e c t of t h i s f o r k e d a l l e l e .  as a r e s u l t  The o t h e r two  s c u t e - L 8 chromosomes w e r e homozygous v i a b l e b u t f e m a l e i t y was 39% o f t h e c o n t r o l  ( i n preparation).  Of t h e s e homo-  zygous s c u t e - L 8 f l i e s , o n l y 1 i n 5 were f e r t i l e maturing f o r extended  lengths of time.  viabil-  even  after  This reduction i n  f e m a l e v i t a l i t y made i t i m p o s s i b l e t o m a i n t a i n a homozygous stock.  I t i s apparent  t h a t the scute-L8 rearrangement  t h e most p r o f o u n d , e f f e c t on v i a b i l i t y  has  and f e r t i l i t y .  The s c u t e - L 8 f e m a l e s were p h e n o t y p i c a l l y s i m i l a r t o t h e s c u t e - L 8 m a l e s w i t h Y-chromosomes.  Macrochaetae  were  dis-  t u r b e d on t h e e n t i r e e p i d e r m i s o f t h e f l y b u t most n o t i c e a b l y on t h e s u r f a c e s o f t h e abdomen.  M i c r o c h a e t a e numbers o v e r -  l a p p e d w i l d t y p e b u t have subnormal a v e r a g e s .  These  females  w e r e a l s o d e v e l o p m e n t a l l y d e l a y e d when c o m p a r e d t o w i l d sibs.  When f e r t i l e ,  type  t h e s c u t e - L 8 f e m a l e t e n d e d t o l a y numerous  86.  e g g s , most o f w h i c h h a t c h e d .  The  X/0  males d e r i v e d from  t h e s e c r o s s e s c o u l d n o t be d i s t i n g u i s h e d f r o m r e c o v e r e d from the p a t e r n a l experiments. a l m o s t denuded o f macrochaetae of  t h e s c u t e gene.  ible The  similar  These f l i e s  males were  by t h e i n c r e a s e d v a r i e g a t i o n  O f t e n , l e s s than 6 macrochaetae  were  vis-  on t h e h e a d and t h o r a x and none were f o u n d on t h e abdomen. m i c r o c h a e t a e w e r e d i s o r g a n i z e d and r e d u c e d  t h e t h o r a x and  d r a m a t i c a l l y reduced  i n number  on t h e abdomen.  on  Although  e x h i b i t i n g a more s e v e r e p h e n o t y p e i n m o s t r e s p e c t s , s c u t e - L 8 a p p e a r s t o m a n i f e s t a l l o f t h e phenomena t h u s f a r a s s o c i a t e d with the other scute  inversions.  The n e x t chromosome e x a m i n e d was n o t a s s o c i a t e d w i t h any p r o b l e m s  scute-V2, which  of female  infertility.  Homozygous f e m a l e s e x p r e s s e d a p h e n o t y p e t h a t was tical  was  almost  t o t h a t e x p r e s s e d by h e m i z y g o u s s c u t e - V 2 m a l e s .  most p r o f o u n d l y a f f e c t e d l o c u s appears d o m i n a l and t h o r a c i c m i c r o c h a e t a e sexes.  A l l o f the macrochaetae  The  t o be a c h a e t e a s  are g r e a t l y reduced  iden-  ab-  i n both  are t y p i c a l l y present i n a  s c u t e - V 2 f e m a l e and a c c e s s o r y b r i s t l e s a r e common on  the  s c u t e l l u m and p o s t e r i o r t h o r a x .  closely  This p a r a l l e l s very  t h e phenotype r e p o r t e d above f o r s c u t e - 8 . M a t e r n a l p r o d u c t i o n of scute-V2/0 d r a m a t i c r e d u c t i o n i n l e t h a l i t y and fold  males r e s u l t s i n a  i s e x p r e s s e d as a  i n c r e a s e i n the r e c o v e r y of these males.  they e x h i b i t  s c u t e v a r i e g a t i o n and  that i s p a r t i c u l a r l y  four-  Phenotypically,  s t r o n g achaete  variegation  e v i d e n t on t h e s u r f a c e s o f t h e abdomen.  87.  Developraentally, these and  X/0 m a l e s a r e n o t s i g n i f i c a n t l y  t h r i v e i n normal c u l t u r e s .  retarded  The s c u t e - V 2 r e s u l t s i n d i c a t e  t h a t m a n i f e s t a t i o n s o f t h e r e a r r a n g e m e n t do n o t a f f e c t ity As nal  t o t h e same e x t e n t  as t h a t seen w i t h the other i n v e r s i o n s .  a r e s u l t o f t h i s m o d e r a t e b a s e l i n e X/0 v i a b i l i t y , e f f e c t d o e s n o t a p p e a r t o be a s p r o f o u n d  experiments.  I t i s evident  i slittle  scute-Si,  maternal  that the recovery approximately  chrowith  Phenotypically, a  extreme example o f t h e s c u t e - L 8 ,  scute-4- g r o u p , a l l o f whom e x h i b i t v a r y i n g  of scute v a r i e g a t i o n .  nal  of  l e t h a l i t y associated  t h e p a t e r n a l l y d e r i v e d X/0 c o n d i t i o n . female i s the l e a s t  repre-  i n v e r s i o n phenomenon.  Homozygous s t o c k s c o n t a i n i n g t h i s  mosome t h r i v e a n d t h e r e  scute-4  as i n p r e v i o u s  i n v e r s i o n s t u d i e d f o r evidence  e f f e c t s was s c u t e - 4 .  the mater-  t h a t t h e s c u t e - V 2 chromosome  s e n t s a moderate example o f t h e s c u t e The f i n a l  viabil-  The r e s u l t s o f t h i s  degrees  study i n d i c a t e  o f m a t e r n a l l y d e r i v e d scute-4/0 males i s  t h e same a s t h e f r e q u e n c y  observed i n the pater-  studies. P h e n o t y p i c a l l y , the X / 0 males d e r i v e d from both  were i d e n t i c a l t h r o u g h o u t t h e p o p u l a t i o n s study  sources  examined i n t h i s  a n d t h e r e w e r e no m a l e s o b s e r v e d t o e c l o s e a f t e r a n *  extended developmental p e r i o d .  Although  scute-4  exhibits a  s c u t e p h e n o t y p e a n d a p p e a r s t o be o f a s i m i l a r o r i g i n ,  this  chromosome i s a t y p i c a l o f t h e chromosomes p r e v i o u s l y s t u d i e d . T h i s a n o m a l y w i l l be d i s c u s s e d the  text.  i n greater detail l a t e r i n  88.  - Chapter 2 X/0  For  Viability  o f Recombinant Scute  Inversions  many y e a r s , D r o s o p h i l a r e s e a r c h e r s h a v e b e e n u s i n g  recombinant  s c u t e chromosomes, w h i c h i n c l u d e a n  interstitial  i n v e r s i o n , a s e f f e c t i v e X-chromosome b a l a n c e r s . two  groups t h a t can i n t e r c o n v e r t t h e i r l e f t  There  and r i g h t  exist chromo-  some e n d s w i t h o u t p r o d u c i n g a n e u p l o i d y f o r e u c h r o m a t i c As  scute-4, scute-Si  and  s c u t e - L 8 have a v e r y s i m i l a r  m a t i c b r e a k , v i a b l e r e c o m b i n a n t s c a n be p r o d u c e d any  c o m b i n a t i o n o f ends.  comprise the o t h e r group will  produce  two  The  inversions  p r e v i o u s s t u d i e s we  and e x c h a n g e b e t w e e n t h e s e  scute-V2 inversions  From t h e  have e s t a b l i s h e d t h a t t h e p a r t i c u l a r c h r o -  mosomes h a v e s p e c i f i c  d e v e l o p m e n t a l p r o f i l e s t h a t a r e depen-  d e n t u p o n t h e i r c h r o m o s o m a l make-up. the  euchro-  exhibiting  s c u t e - 8 and  d i f f e r e n t , v i a b l e recombinants.  genes.  This investigation  of  various recombinants provides a f u r t h e r d i s s e c t i o n of the  mechanisms c o n t r i b u t i n g t o the m a t e r n a l e f f e c t  phenomenon.  T a b l e 4 and F i g u r e 5 p r e s e n t r e s u l t s c o n c e r n i n g t h e bility  o f X/0  i n d i v i d u a l s i n h e r i t i n g these recombinant,  viascute  i n v e r s i o n chromosomes e i t h e r f r o m t h e f e m a l e o r f r o m t h e m a l e parent.  Originally,  t h e phenomenon was  d i s c o v e r e d a s an i n -  c i d e n t a l f i n d i n g i n s t u d i e s on compound a u t o s o m e s ( H a r g e r , 1974).  At t h a t time, Harger observed t h a t the scute i n v e r -  s i o n , b a l a n c e r chromosome, d e s i g n a t e d B a s e , was v i a b l e i n t h e X/0  f a r more  c o n d i t i o n when t h e s c u t e X-chromosome  was  TABLE 4 X/0 M a l e V i a b i l i t y i n S c u t e X-chromosome R e c o m b i n a n t s Paternal Effect  CONTROL Sex Ratio S1L  N  EXPERIMENT Sex Ratio  N  Sex Ratio  N  1.06  1279  0.87  3141  0.11  2053 3266  1.04-  993  0.95  4107  0.10  2316  O.98  11.14-  0.88  2492  1.05  977 828  0.14  1962  1.07  1273  0.93  2119  1.13  783  0.18  3856  1  .15  1535  1.11  3401  L8R  1.07  815  0.47  2182  1.04-  1295  O.96  1844  V2R  1.17  887  O.76  1  .12  1280  1.05  1328  0.93  516  0.68  2589 1071  1 .08  713  1.13  1.02  1484  0.17  Base  0.93  1777  Binsc  O.96  Insc vincy  S1L  Sex Ratio  EXPERIMENT  SC  asc  S1L  N  CONTROL  Effect  8R  :  S1L  Maternal  sc sc sc  4R  952  TABLE 4  Continued  CONTROL Sex Ratio sc sc sc sc  sc sc sc sc  sc sc  L8L L8L L8L L8L  4L 4L 4L  sc sc sc sc  sc sc sc  SIR 8R V2R 4R  SIR L8R 8R  0.86  EXPERIMENT  N 792  Sex Ratio  N  CONTROL Sex Ratio  EXPERIMENT  N  Sex Ratio  N  0.04  1463  0.93  729  O.39  1004-  0.98  1288  0.06  2801  0.97  1205  0.92  2663  1.16  1313  0.81  1314  1.26  953  1.03  1668  0.93  877  0.51  1103  1.11  820  1.05  1381  O.92  1106  0.00  938  1.16  938  0.00  711  1.10  1679  0.00  4360 0.81  1017  4L  V2R . sc  0.86  538  0.44  1712  1.08  699  8L  V2R sc  0.98  1716  0.11  2316  O.93  1514  0.83  2119  V2L  8R sc  1.17  1286  0.20  1977  1.14-  1030  1.06  1475  91.  FIGURE 5  X/0  viability  of scute  X-chromosomes o f d i f f e r e n t  recombinant parental  origin  Paternally derived X  -  unlined  Maternally  -  lined  derived X  92.  SEX 1 0  2 0  3 0  RATIO  5 0  4 0  6 0  70  8 0  9 0  100  110  11 9 5  Base  18  in  v i nscy  /  /  /  /  /  /  /  /  /  / /  /  47 9 6  S I L L8R  L 8 L SIR  /  /  /  /  /  —j  /  ZL  7  /  r  /  /  /  /  /  /  /  3 9  44 81  4L  V2R  / / . / / /  /  /  /  /  / ~ 7  11 83  8L  V2R  /  /  /  /  /  /  2 0 106  V2L 8 R  /  /  /  /  /  /  /  /  /  /  A  120  130  93-  i n h e r i t e d f r o m a homozygous B a s e f e m a l e . H a r g e r ' s f i n d i n g s h a v e "been r e e x a m i n e d  I n these  studies,  and extended  to include  a number o f a d d i t i o n a l b a l a n c e r chromosomes o f t h e c o n s t i t u t i o n scute-Si  left  - scute-8 r i g h t ,  r a n g e m e n t w i l l be t e r m e d  and h e r e a f t e r  this  rear-  S 1 L 8R.  The r e s u l t s f o r t h i s chromosome i n d i c a t e a c o n s i s t a n t , marked m a t e r n a l e f f e c t t h a t r e p r e s e n t s a s i x t o t e n - f o l d f e r e n c e between p a t e r n a l  dif-  d e r i v a t i o n and m a t e r n a l d e r i v a t i o n .  I n a l l c a s e s , m a t e r n a l i n h e r i t a n c e o f t h e X-chromosome r e s u l t s in negligible lethality  o f X/0 m a l e s .  n a l d e r i v a t i o n r e s u l t s i n 80 - 90$  I n contrast, the pater-  lethality  of these  individ-  uals . Phenotypically, ance o f s c u t e - S i  S 1 L 8R/0 m a l e s p a r t i a l l y m i m i c t h e a p p e a r -  individuals.  w i t h t h i s recombinant  The m a j o r p h e n o t y p e  involves aberrations  such as the s c u t e l l a r b r i s t l e s .  of the  associated macrochaetae  I t s h o u l d be m e n t i o n e d  that  t h e s c u t e p h e n o t y p e i s l e s s s e v e r e i n S 1 L 8R t h a n i n s c u t e - S i . The a c h a e t e v a r i e g a t i o n a p p e a r s  t o be s i m i l a r i n b o t h c a s e s .  D e v e l o p m e n t a l l y , t h e S 1 L 8R/0 to mature t h a n t h e normal progeny When p a t e r n a l l y d e r i v e d ,  t h e s e X/0  i n d i v i d u a l s a r e much s l o w e r present i n the experiment. males o f t e n eclose  several  d a y s l a t e r a n d show s e v e r e s c u t e a n d a c h a e t e p h e n o t y p e s . t e r n a l l y derived,  t h e p h e n o t y p e i s e s s e n t i a l l y t h e same a s  scute-Sl/O males except t h a t t h e macrochaetae more f r e q u e n t l y .  Ma-  T h i s may be e x p l a i n e d  are expressed  b y t h e chromosome  s t i t u t i o n that occurs i n t h i s recombinant.  con-  Owing t o t h e f a c t  94.  t h a t t h e s c u t e - 8 and. s c u t e - S i  euchromatic breakpoints are  s t a g g e r e d on e i t h e r s i d e o f t h e s c u t e l o c u s , t h e S1L b i n a n t c a r r i e s a d u p l i c a t i o n f o r t h e s c u t e gene. cal  recombinant  i n t h e S1L  8R/0  s c u t e phenotype  m a l e may  a s t h e two  The  result  maintenance  recipro-  o f two  scute  i n a r e d u c t i o n o f mutant  l o c i t o g e t h e r may  gene p r o d u c t t o s h i f t t h e p h e n o t y p e  contribute  towards w i l d .  h a i r y w i n g e f f e c t i s commonly e x p r e s s e d i n S 1 L and  The  recom-  8L SIR n o r m a l l y c a n n o t be r e c o v e r e d a s i t i s  d e f i c i e n t f o r the scute region. loci  8R  enough  In fact,  8R  homozygotes  hemizygotes. The  v e r y l a t e e c l o s i n g X/0  males from the p a t e r n a l  exper-  i m e n t s showed f e e b l e n e s s and a n i n a b i l i t y t o c o n t r o l w i n g leg  f u n c t i o n s , much t h e same a s was  experiments.  Very often these f r a i l  dead i n the f o o d . of  a  flies  wings;  seen w i t h p r e v i o u s p a t e r n a l i n d i v i d u a l s were  I t i s an i n t e r e s t i n g p o i n t t h a t t h e  t h e r e f o r e , upon e c l o s i o n , t h e s e f l i e s  must be  majority their  severely  These o b s e r v a t i o n s and t h e o t h e r d e v e l o p m e n t a l  data s t r o n g l y suggest t h a t the recombinant  S1L  c h a r a c t e r i s t i c s f r o m b o t h o r i g i n a l chromosomes. first  found  t r a p p e d i n t h e f o o d do n o t s u r v i v e t o " e x p a n d "  debilitated.  or  8R m a i n t a i n s T h i s i s the  i n d i c a t i o n t h a t b o t h ends o f t h e r e c o m b i n a n t  chromosome  c o n t r i b u t e s i g n i f i c a n t l y t o t h e p h e n o t y p i c make-up. The  r e c o m b i n a n t , S1L L8R,  w o u l d be e x p e c t e d t o be  largely  l e t h a l i n t h e p a t e r n a l l y d e r i v e d e x p e r i m e n t s and 2 0 - 4 - 0 % v i a b l e i n the maternal experiments. the  case.  The  T h i s apparently i s not  p a t e r n a l d o n a t i o n o f t h e X-chromosome  results  95.  i n a k7%  viability  d u c e s 96%. to  One  o f X/0  would  males w h i l e maternal donation pro-  a l s o e x p e c t homozygous S1L L8R  express reduced f e r t i l i t y  t h i s was  not the case.  and  In fact,  females  show p o o r v i a b i l i t y .  However,  t h e homozygous S1L L8R  females  w e r e e q u a l l y a s v i a b l e and a s f e r t i l e a s t h e c o n t r o l  females.  T h i s p o s e s a n e n i g m a when one  stocks.  c o n s i d e r s the p a r e n t a l  P h e n o t y p i c a l l y , the stock i s scute-Si although the abdominal  bristle  i n appearance,  p a t t e r n s a r e somewhat more  s e v e r e l y a f f e c t e d a s s e e n i n s c u t e - L 8 . • The X/0  individuals  are  developmental  m o d e r a t e l y a c h a e t e and  strongly scute.  The  d e l a y i s s i g n i f i c a n t l y r e d u c e d when c o m p a r e d t o e i t h e r o f t h e parental inversions. the It  The  S1L L8R/0 m a l e s a r e r a r e l y f o u n d i n  f o o d and a r e n o t a s s o c i a t e d w i t h e x t e n d e d seems l i k e l y  t h a t the d i f f e r e n c e between the  chromosomes and t h i s r e c o m b i n a n t e f f e c t s i n each  r e c o m b i n a n t s S1L V2R  a t e l y good v i a b i l i t y  resides i n specific  and S1L 4R b o t h e x h i b i t moder-  The  phenotypes  for  i n o r i g i n a l t h o u g h b o t h m a l e and f e m a l e S1L  o u t t h a t b o t h S1L V2R lication  The  V2R  developmental  o f t h e s e i n d i v i d u a l s i s much t h e same a s was  t h e p r e v i o u s r e c o m b i n a n t , S1L L8R.  viability  are predominantly  i n d i v i d u a l s show s t r i k i n g l y m u t a n t abdomens. profile  marker  recombinant.  when d e r i v e d p a t e r n a l l y and f u l l  when d e r i v e d m a t e r n a l l y . scute-Si  parental  s t r a i n o r i s a f u n c t i o n o f t h e new h e t e r o c h r o -  matic f e a t u r e s generated i n the The  development.  observed  I t s h o u l d be p o i n t e d  and S1L 4R c o n t a i n a c o n s i d e r a b l e dup-  o f p r o x i m a l X h e t e r o c h r o m a t i n and t h i s may  contribute  96.  t o an a l t e r a t i o n o f t h e e x p r e s s i o n o f t h e v a r i e g a t i n g The n e x t g r o u p  of recombinant  loci.  chromosomes i n v o l v e d t h e  l e f t p o r t i o n o f s c u t e - L 8 . The chromosome L 8 L SIR p r o d u c e s phenotype  v e r y s i m i l a r t o scute-L8 as the macrochaetae  l a r g e l y a b s e n t and t h e a b d o m i n a l at a l l .  are  r e g i o n s have few b r i s t l e s  P a t e r n a l l y , t h i s chromosome i s v e r y l e t h a l a n d m a t e r -  n a l l y the v i a b i l i t y r e t u r n s t o one-third of the normal. d e v e l o p m e n t a l d e l a y i s marked i n t h i s ilar  a  to that  profile  s t o c k and i s v e r y sim-  seen i n t h e p a r e n t a l s t o c k s .  i s somewhat c r y p t i c  This  as the r e c i p r o c a l  viability  recombinant  S1L L8R h a s s u c h a d i s t i n c t l y d i f f e r e n t d e v e l o p m e n t a l One may  The  profile.  suggest t h a t t h e s e r e c o m b i n a n t s have i s o l a t e d t h e  l e t h a l i t y f a c t o r s on t h e L 8 L S I R chromosome a n d h a v e g r e a t l y e l i m i n a t e d t h e m f r o m t h e S 1 L L8R r e c o m b i n a n t .  Further inves-  t i g a t i o n i s necessary to determine the nature of t h i s The L 8 L 8R chromosome i s e x t r e m e l y l e t h a l when p a t e r n a l l y b u t shows l i t t l e female. ified  anomaly.  donated  e f f e c t when t r a n s f e r r e d f r o m  a  P h e n o t y p i c a l l y , t h e s e X/0 i n d i v i d u a l s e x h i b i t a mod-  scute-L8 expression of b r i s t l e s .  p r a c t i c a l l y b a l d w h i l e t h e head,  Abdominal  regions are  t h o r a x and s c u t e l l a r r e g i o n s  e x p r e s s many o f t h e n o r m a l b r i s t l e s .  Developmentally, the  c o n t r a s t between m a t e r n a l e f f e c t and p a t e r n a l e f f e c t i s g r e a t e s t f o r t h i s p a r t i c u l a r chromosome.  Paternally  derived  X/0 m a l e s a r e e x t r e m e l y s l o w d e v e l o p i n g a n d many e c l o s e l a t e and u s u a l l y d i e i n t h e f o o d .  M a t e r n a l l y d e r i v e d X/0  males  are slower i n d e v e l o p i n g than w i l d type, but n o t as d r a s -  97-  tically  d e l a y e d as w i t h the p a t e r n a l o r i g i n .  other recombinants, i t appears different  8R  i s fundamentally  t h a n e i t h e r o f i t s p a r e n t a l chromosomes a s  by the d e v e l o p m e n t a l The  t h a t L8L  As w i t h t h e  suggested  data.  r e c o m b i n a n t s , L 8 L V2R  and L 8 L  p h e n o t y p e a l t h o u g h much r e d u c e d  4R,  exhibit a  i n t h e L 8 L V2R  scute-L8  individuals.  T h e s e chromosomes a r e r e a s o n a b l y v i a b l e when d o n a t e d male p a r e n t and a r e f u l l y male p a r e n t . L8L  4R  A s w i t h t h e S1L  r e c o m b i n a n t s , b o t h L 8 L V2R  carry large heterochromatic duplications that  different right  males.  but i s m o d i f i e d i n the presence  in  of the  ends.  Recombinants t h a t i n v o l v e the d i s t a l chromosome o f f e r a s p e c i a l  end  of the  s i t u a t i o n as t h e y r e s u l t  scute-4 i n X-chro-  mosomes t o t a l l y l a c k i n g a n u c l e o l u s o r g a n i z e r r e g i o n . individuals  and  likely  i s e v i d e n t t h a t the scute-L8 phenotype predominates  these recombinants  a  v i a b l e when c o n t r i b u t e d b y t h e f e -  m o d i f y t h e i r p o s i t i o n e f f e c t e x p r e s s i o n i n t h e X/0 It  by  survive i n the presence  These  o f a Y-chromosome o r  some o t h e r s o u r c e o f rDNA b u t a r e e n t i r e l y l e t h a l  without  a c c e s s o r y r i b o s o m a l genes.  recombinants  are  moderately  P h e n o t y p i c a l l y , these  scute but not a p p r e c i a b l y achaete.  Generally,  these f l i e s  show a s c u t e p h e n o t y p e i n t e r m e d i a t e b e t w e e n  s c u t e - 4 and  scute-Si.  4 L _ 8 R , 4 L L8R)  Three of the recombinants  were e n t i r e l y bobbed l e t h a l  were e v e r r e c o v e r e d .  The  4 L 8R  experiments  (4L  a s no x/0  SIR, flies  showed a g r e a t  d e a l o f n o n d i s j u n c t i o n a s s o c i a t e d w i t h the male m e i o t i c  events  98.  and t h i s h a s "been d i s c u s s e d p r e v i o u s l y i n t h e (Yamamoto and M i k l o s , 1977).  literature  I t i s i n t e r e s t i n g that the r e -  m a i n i n g two b o b b e d l e t h a l s g e n e r a t e d e x h i b i t a much r e d u c e d l e v e l o f n o n d i s j u n c t i o n a s c o m p a r e d t o 4-L 8 R . reflects specific  This  likely  differences i n heterochromatic content bet-  ween t h e t h r e e e x a m p l e s .  T h i s o b s e r v a t i o n w i l l be o f p a r t i c -  u l a r i n t e r e s t to those studying the r o l e of heterochromatin i n chromo some p a i r i n g . The  f i r s t i n d i c a t i o n of the p e c u l i a r heterochromatic  b r e a k i n s c u t e - V 2 was first  encountered i n t h i s experiment.  d i s c o v e r e d t h a t t h e r e c o m b i n a n t 4 L V2R  I t was  was n o t a b o b b e d  l e t h a l , w h i c h s t r o n g l y s u g g e s t e d t h a t t h e V2R  end o f t h e  X-chromosome c o n t a i n e d s u f f i c i e n t r i b o s o m a l g e n e s t o m a i n t a i n a non-mutant phenotype  i n a n X/0  fly.  V2L  8R chromosome and i t s s u b s e q u e n t  the  left  end o f t h e V2  The  g e n e r a t i o n of the  viability  suggested  that  chromosome a l s o c a r r i e d a c o n s i d e r a b l e  number o f r i b o s o m a l g e n e s .  T h e s e two  f o r m a t i o n o f two h y p o t h e s e s :  observations l e d to the  e i t h e r s c u t e - V 2 was  originally  b r o k e n i n t h e m i d d l e o f t h e r i b o s o m a l c l u s t e r o r t h e chromosome was n o t a s i m p l e X i n v e r s i o n and was in  a complex  organizer.  rearrangement  previously  t h a t secured the second  involved  nucleolus  For the purposes of t h i s d i s c u s s i o n , the  former  e x p l a n a t i o n w i l l be a d o p t e d o w i n g t o i t s s i m p l i c i t y and  test-  ability. The  4 L V2R  recombinant  showed m o d e r a t e v i a b i l i t y  p a t e r n a l l y d e r i v e d and a l m o s t n o r m a l v i a b i l i t y  when  when m a t e r n a l l y  99.  inherited.  The X/0 m a l e s w e r e v i g o r o u s and showed v e r y  little  d e v e l o p m e n t a l d e l a y a s c o m p a r e d t o t h e f e m a l e s o f t h e same experiment.  P h e n o t y p i c a l l y , t h e s e f l i e s w e r e o f t h e scute-4-  mutant c o n d i t i o n , ligible  showing macrochaetae  d i s t u r b a n c e s but neg-  e f f e c t on m i c r o c h a e t a e .  The r e m a i n i n g r e c o m b i n a n t s B o t h chromosomes p r o d u c e d  s t u d i e d w e r e V2L 8R a n d 8L V2R.  a s t a n d a r d m a t e r n a l e f f e c t a n d showed  d e v e l o p m e n t a l p r o f i l e s t h a t were c o n s i s t e n t f o r t h e p a r e n t a l chromosomes.  The V2L 8R chromosome i s m a r k e d l y  e p i d e r m a l s u r f a c e s i n t h e X/0, X/Y  a n d X/X  i s n o t o b s e r v e d i n t h e 8L V2R r e c o m b i n a n t t l e s were l a r g e l y n o r m a l  a c h a e t e on a l l  conditions. where a c h a e t e  e x c e p t f o r t h e X/0 m a l e s .  f r e q u e n t l y observed mutant phenotypes  This bris-  The most  i n 8L V2R were m i s s i n g  s c u t e l l a r b r i s t l e s and t h e p r e s e n c e o f a c c e s s o r y t h o r a c i c bristles.  100.  -Chapter  3 -  Maternal E f f e c t s of Inversion  The  purpose  of the next  s e t o f e x p e r i m e n t s was  the e f f e c t of the maternal genotype, i n h e t e r o c h r o m a t i n and/or s i o n o f s c u t e X/0  to  test  deficient  on t h e  suppres-  P r i o r to these experiments,  m a t e r n a l e f f e c t had b e e n d e m o n s t r a t e d  t h e m a t e r n a l e f f e c t was  when i t was  the r i b o s o m a l genes,  lethality.  scute i n v e r s i o n females.  Heterozygotes  the  o n l y f o r homozygous  I t seemed w o r t h w h i l e t o p r o v e a g e n e r a l phenomenon t h a t  f r o m t h e s c u t e i n v e r s i o n b e i n g i n h e r i t e d from any  that  resulted female  r a t h e r than a s p e c i f i c p e c u l i a r i t y of scute females. E a c h o f t h e s c u t e chromosomes s t u d i e d w e r e made h e t e r o z y g o u s w i t h e a c h o f t h e f o l l o w i n g X-chromosomes: Df(l)  b b - 4 5 2 , b b - 2 - r l - 3 , X-Y 2 1  X-chromosome m a r k e d w i t h v _ . itered for their viability males. and  The  subsequent  compared t o t h e i r  N0~,  8  ( a n a t t a c h e d X j Y ) and a s t a n d a r d The  r e s u l t i n g f e m a l e s were  and t h e n m a t e d t o X-Y/O  progeny  sc^sc ^  and X•Y/Y  were s c o r e d e v e r y second  standard sibs.  The  mon-  sex r a t i o s  day  entered  i n T a b l e 5 w e r e c a l c u l a t e d by c o m p a r i n g  the v i a b i l i t i e s  t h e X/0  females recovered  males w i t h the v i a b i l i t y  o f X/X  of  f r o m t h e same c r o s s . The  v a l u e s presented i n Table 5 suggest t h a t the  maternal  e f f e c t i s i n d e e d a g e n e r a l phenomenon r e s u l t i n g f r o m t h e g e n der of the scute X donating p a r e n t . ery  o f X/0  I n a l l cases, the recov-  males from h e t e r o z y g o u s f e m a l e s r e s u l t e d i n enhanced  TABLE 5 X/0  V i a b i l i t y from Heterozygous Scute  s c ^ s c NO"  D f ( l ) bb 452  Sex Ratio  N  Sex Ratio  +dl49  1.17  1008  1.08  847  1-03  566  1.23  1619  cv v f  0.00  0  0.00  0  0.00  0  0.00  468  8  sc  8  Q  sc  1  bb  2 r 1  Sex Ratio  N  "  Females X-Y  3  Sex Ratio  N  N  Sex Ratio  N  1-18 538 0.00  715  CM  sc  1  sc sc  L 8  sc  L 8  0.36 2516  +S  O.37  0.00  sn  0.24  538  0.18  369  0.31  0.16  609  0.24  916  0.93  831  I . 0 3 1239  m  0.00  1611  +di49 3  0  0.40  0  1238  0.00  0.4-6 1406  0.31  983  0.00 • 656  0.00  716  0.17  648  0.21  898  0.26  781  0.19  682  0.22  674  1.13  772  0.86 1640  1.07  1.05  679  O.96  o  513  v? sc  c  1310  4 sc  0.94 1016  1.13  765  1172  O.83  844  TABLE 5  Continued  sc  4  8  sc  NO-  D f ( l ) bb 4-52 1  ,, bb 2 r l - 3  Sex Ratio  X-Y  Sex Ratio  Sex Ratio  N-  Sex Ratio  N  0.88  2713  1.04  I838  0.91  2063  1.24  1616  O.96  1082  S1L L8R  0.81  615  O.87  783  0.90  912  0.99  836  0.91  650  S1L  V2R  0.84  911  0.97  916  0.91  583  1.13  654  1.06  575  S1L  4R  1.14  475  0.90  726  1.08  830  1.16  610  1.04  772  L8L  8R  O.96  745  O.92  555  0.81  538  0.84  ' 664  0.91  764-  0.22  601  0.31  399  0.46  716  0.26  633  S1L  8R  Sex Ratio  N  N  N  L8L SIR  0-37  L8L  V2R  1.18  940  0.90  1056  1.09  949  0.99  788  1.07  561  L8L  4R  0.80  592  0.95  539  0.84  670  1.06  1008  0.97  717  4L V2R  0.71  628  0.88  786  0.79  983  1.01  686  0.85  428  V2L  8R  1.09  1117  0.98  492  O.92  1122  1.06  711  0.97  596  8L V2R  0.82  841  O.77  1083  0.86  665  O.94  720  0.89  388  1219  103-  v i a b i l i t y when c o m p a r e d t o r e c o v e r y o f X/0 m a l e s i n t h e p a ternal is  experiments.  The m a g n i t u d e o f t h i s m a t e r n a l  c o m p a r e d w i t h m a t e r n a l e f f e c t s f r o m h o m o z y g o t e s and t h e  paternal effects F i g u r e 6. effect  (i.e.  p a t e r n a l l y d e r i v e d X-chromosomes)  i n the heterozygote experiments  l e s s than that observed  The r e s c u e o f t h e X/0 iments appeared  of  a n d may  reflect parental  males i n these heterozygote  t o be i n d e p e n d e n t  Xhomologue.  Two  effect. exper-  of the composition of the  o f t h e chromosomes  bb"*"-4-52) w e r e c o m p l e t e l y d e f i c i e n t  (sc^sc ^ 8  i n ribosomal  N0~,  DNA  d i d n o t show a n y p a r t i c u l a r i n f l u e n c e on t h e v i a b i l i t i e s t h e i r X/0 p r o g e n y .  A third  chromosome,  a v e r y s m a l l p o r t i o n o f t h e r i b o s o m a l RNA  bb-2-rl-3»  carries  genes which  i s in-  s u f f i c i e n t t o m a i n t a i n d e v e l o p m e n t i n a n X/0  condition.  chromosome a l s o d i d n o t show a n y p e c u l i a r e f f e c t nal  These  The k e y f e a t u r e r e v e a l e d b y t h e s e e x p e r i m e n t s i s  the u n i v e r s a l i t y of the maternal  non-scute  X/0  i s often marginally  s e g r e g a t i o n d i f f e r e n c e s between t h e d i f f e r e n t  stocks.  Df(l)  The  i n t h e homozygote e x p e r i m e n t s .  differences are frequently i n s i g n i f i c a n t slight  in  The most o b v i o u s o b s e r v a t i o n i s t h a t t h e m a t e r n a l  i s of s i m i l a r magnitude i n a l l experiments.  viability  and  effect  r e s c u e o f X/0 m a l e s .  considering the v i a b i l i t y  A point of interest of specific  i n d i v i d u a l s c a r r y i n g the scute-Si  chromosome.  The  on t h e m a t e r -  a r i s e s when  heterozygotes.  Those  i n v e r s i o n p l u s the dl49  i n v e r s i o n w e r e f o u n d t o be i n v i a b l e bobbed l e t h a l  This  i n the presence  of a  s c u t e - 8 chromosome m a r k e d w i t h  104.  FIGURE 6  • V i a b i l i t y o f s c u t e i n v e r s i o n X/0  males  d e r i v i n g t h e i r X-chromosomes f r o m h e t e r o z y g o u s a n d homozygous f e m a l e s o r hemizygous  Paternal  inheritance  -  unlined  (homozygous)  -  lined  (heterozygous)  -  shaded  Maternal inheritance Maternal inheritance  males.  105. SEX 10  20  30  40  50  RATIO 70  60  90  80  100  110  120  130  12  sc  127  8  / /  49  dl  /  /  /  /  /  /  / 117  42  sc  s l  /  +S  /  /  /  / 36  29  SC  L 8  sn  3  / /  / 24 26 118  .V2  /  SC  /  /  /  /  /  /  /  /  /  / _/  /  /  93 11 95  SIL 8R  /  /  ,/  /' /'  /  /  /  /  /  /  /  47  SIL L8R  I  /  / / / / / / /  /  /  /  96  81  39  L8LSIR 37 44  81  4L V2R  /  / /  /  /  /  /  /  / 71  20  '  V2L 8R  106  '' / /  /-V/  109  11 83  8L V2R  /  /  /  /  /  /  A 82  4 8 from SC SC NO heterozygotes  140  106.  cv v f presented these for  specific  chromosomes  viability.  r i b o s o m a l DNA  t h e same r e s u l t s .  The d a t a s u g g e s t  require additional ribosomal  Studies indicate that a f u l l i s present  sence o f " s i l e n t " mechanism  The s e c o n d  genes and t o d e t e r m i n e  f a c t o r that proved  4-L  of  The chromosome s c  of l i t t l e  for  significance i n the maternal  8R  sc  i s d e f i c i e n t f o r the m a j o r i t y  the proximal X heterochromatin  organizer region.  the  suppression.  was t h e q u a n t i t y o f h e t e r o c h r o m a t i n p r e s e n t  genome.  further  i n progress to v e r i f y the pre-  r i b o s o m a l RNA  of t h e i r  of  ( B a k e r , 1972).  i n t h e s e chromosomes  a r e now  genes  complement  The p o s s i b l e muted e x p r e s s i o n o f t h e s e g e n e s m e r i t s s t u d y and e x p e r i m e n t s  that  i n c l u d i n g the nucleolus  D f ( l ) bb -452 a n d b b - 2 - r l - 3 a r e d e f i c i e n t 1  t h e bobbed r e g i o n b u t n o t f o r s i g n i f i c a n t p o r t i o n s o f p  heterochromatin.  The x_  tered heterochromatic  chromosome c a r r i e s a s t a n d a r d , u n a l -  r e g i o n w h i l e t h e X • Y chromosome  carries  proximal X heterochromatin plus a large p o r t i o n of the Y heterochromatin.  The c o m p a r i s o n  of X/0 v i a b i l i t y  d e f i c i e n t i n heterochromatin w i t h females  from  females  w i t h excess  hetero-  c h r o m a t i n y i e l d s a s m a l l d i f f e r e n c e between t h e two. The p h e n o t y p e s o f t h e X / 0 i n d i v i d u a l s w e r e v e r y to  those observed  ments.  .of  maternal  effect  experi-  G e n e r a l l y , t h e v a r i e g a t i n g g e n e s were n o t s e v e r e l y  expressed ful  i n t h e homozygous  similar  and t h e X / 0 m a l e s were a l w a y s  i n t e r n a l c o n t r o l i n these homologous m a l e s .  One  competitive.  A  use-  s t u d i e s was t h e e c l o s i o n p e r i o d  c a n e a s i l y s e e two o v e r l a p p i n g d i s -  .107-  tributions;  one r e p r e s e n t i n g n o r m a l m a l e s a n d a n o t h e r  i l l u s t r a t i n g the delayed  scute males.  c l e a r l y demonstrate t h a t matroclinous u a l s s u r v i v e w e l l whether t h e i r  These  experiments  s c u t e X/0  individ-  s c u t e X-chromosome i s  d e r i v e d f r o m a homozygous o r h e t e r o z y g o u s f e m a l e  parent.  T h u s , i t a p p e a r s t h a t t h i s phenomenon i s a s s o c i a t e d  with  the gender o f t h e f l y r a t h e r t h a n an anomaly p e c u l i a r t o the  scute  inversions.  The r e s e a r c h  also suggests  the maternal "rescue"  associated with parental  a n c e o f t h e s c u t e X/0  c o n d i t i o n i s somewhat  that  inherit-  insensitive  t o m o d i f i c a t i o n s i n t h e amount o f X o r Y c h r o m o s o m a l heterochromatin ter  i n t h e m a t e r n a l genome.  The n e x t  chap-  i s d e v o t e d t o a more t h o r o u g h a n a l y s i s o f t h e e f f e c t s  of heterochromatin  on s c u t e X/0  viability.  108.  - Chapter  4 -  M o d i f i c a t i o n o f the x/0  Viability  b y X-Chromosome H e t e r o c h r o m a t i c D u p l i c a t i o n s and A l t e r e d  The of  next  series of studies involved the i n v e s t i g a t i o n  s c u t e X/0 v i a b i l i t y  fragments.  Y-Chromosomes  i n the presence  These rearrangements  of specific  chromosome  c a r r y a number o f f a c t o r s  that are reported to a f f e c t the expression o f scute mutations. All  o f these supernumerary fragments  are predominately  hetero-  c h r o m a t i c . . The Y b b ~ , Dp 1 3 3 7 a n d Dp 1 1 8 7 a r e d e v o i d o f rRNA c i s t r o n s w h i l e Dp 8 5 6 a n d t h e s t a n d a r d Y-chromosome h a v e a full  complement o f t h e s e genes.  There i s a l s o a s m a l l  euchro-  m a t i c d u p l i c a t i o n c o n t a i n i n g t h e s c u t e l o c u s on Dp 1 3 3 7 a n d Dp 8 5 6 .  The e u c h r o m a t i c  d u p l i c a t i o n on Dp 1187 c o v e r s v_ b u t  does n o t i n c l u d e s c u t e . The  first  s e t of crosses i n v o l v e d mating  females c a r r y i n g t h e fragment  to the standard scute  m a l e s and d e t e r m i n i n g t h e v i a b i l i t y ment c a r r y i n g m a l e s . ternal lethality to  compound-X  o f t h e subsequent  by t h e s p e c i f i c  fragments.  I t was n e c e s s a r y  u s i n g two g e n o t y p i c a l l y  f e r e n t donor females as t h e m a t e r n a l c o n s t i t u t i o n  dif-  influences  (see Chapter 5 ) •  T a b l e s 6 and 7 p r e s e n t d a t a c o n c e r n e d of  frag-  T h i s t e s t s the m o d i f i c a t i o n o f the pa-  d u p l i c a t e these experiments  t h e X/0 v i a b i l i t y  inversion  t h e X/0 v i a b i l i t y  i n the presence  with the a l t e r a t i o n  of specific  chromosomal  TABLE 6 A l t e r a t i o n of  P a t e r n a l E f f e c t b y D u p l i c a t i o n s a n d A l t e r e d Y's Y  0  Sex Ratio sc sc sc  SI  Sex Ratio  N  Dp 1187  Dp  s c " NO"  sc  I  , Sex Ratio  N  1337 +  Sex Ratio  yB  0.04  2004  O.89  2068  0.47  638  O.38  813  0.53  m  0.01  1859  0.82  1862  0-35  826  0.18  735  0.09  2616  1.23  2311  0.85  498  0.49  0.11  2565  0.97  3269  0.77  618  V2  0.29  2371  1.08  1545  0.89  4 '  0.86  2893  0.97  2629  1.13 .1684 1.05  TJ  L8  8 ^ +  sc sc  N  Sex Ratio  Ybb"  + dl49  8  NO"  N  Dp +  sc Sex Ratio  8^6 N0  +  N  704  O.59  550  0.42  0.42  728  538  1  913 .20 694  1.13  509  0.35  855  1.24  580  1.18  892  811  0.61  669  1  .17  804  1.06  738  1.06  936  1.03  l'.12  727  1 .22  610  0.82  591  0.41  639 920  0.18  555  0.26  641  1217  1.00  783  0.94  746  0.40  725  0.42  866  1617  O.89  660  O.36  866  0.10  634  0.18  650  sc S1L  8R  0.09  S1L  V2R  O.79  1935 1610  L8L  8R  0.08  2069  0.95  L8L  V2R  0.48  1262  1.06  988  0.92  816  0.68  807  0.09  580  0.16  718  V 2 L 8R  0.20  1299  1.17  744  0.96  0.44  504  0.60  596  0.66  838  8L V2R  0.11  1043  O.98  912  0.69  533 800  O.56  777  0.77  O.76  809  4L V2R  0.44  1690  0.86  1014  0.83  691  0.69  562  755 0.39 690  0.18  713  ( sc /Y x  x  C ( 1 ) R M yw/Dp )  TABLE 7 A l t e r a t i o n o f P a t e r n a l E f f e c t b y D u p l i c a t i o n s and A l t e r e d Dp :1187  Ybb  Y  0  s c " N0" Sex Ratio  N  Sex Ratio  yB  0.06  2317  0.94  2734  m  0.07  1713  0.86  0.26  1618  0 .26  V2  4  sc sc sc  S 1  L8  8  sc sc  8  +  + dl49  Dp :1337 + N0" sc Sex Ratio  Dp + sc  N0  +  , Sex Ratio  N  0.63  915  0.27  483  0.24  566  0.34^  628  1239  0.49  729  0.17  609  0.21  841  0.39  992  1.09  1633  0.61  967  0.35  707  787  0.53  580  2577  1.03  1691  0.55  707  816  692  0.47  836  O.39  1370  1.02  1535  0-73  619  0.33 0.47  0.39 0.51  712  0.77  920  0.84  583  0.89  1168  O.96  1787  0.83  682  0.83  498  o'.9i  549  1.06  491  0.99  0.49  859  0.30  817  0.16  700  0.11  1.09  0.90  538  0.82  541  0.50  945  0.61  717 662  0.68  647  0.25  619  0.09  710  0.05  488  0.20  944  0.39  0.47  906  0.65  579 608  593 662  O.56  720  0.22  853  sc SIL  8R  0.26  SIL  V2R  0.80  1509 1882  L8L  V2R  0.16  1025  0.92  1573 1616  L8L  8R  960  1.05  1382  0.87  629  0.60  V2L  8R  0.55 0.16  1306  1  1348  593  0.23  8L V2R  0.17  911  O.96  962  0.55 0.71  833 652  567  0.25  544  0.60  4L V2R  0.37  1250  1.02  829  0.68  539  0.41  708  0.13  .10  906  ( C ( 1 ) R M yvpn/Dp  x  sc /Y x  )  N  Sex Ratio  856  N  N  Sex Ratio  Y's  N  FIGURE 7  E f f e c t o f Ybb l o c u s , and  heterochromatic  the v i a b i l i t y  I  :  Paternal  , an a d d i t i o n a l  scute  duplications  on  of scute X / 0 males.  inheritance  of scute  inversion  112.  120  110  100  90  sex ratio  80  70  60  50  40  30  20  10  S1  SC  n  y B  sc+ dl 49 8  Bars represent: X/0,  S1L  ( l e f t to  Dp 1187 ( s c " , b b " ) , Dp 1337 ( s c , +  Ybb .  8R  right) b b " ) , Dp 856 ( s c , +  bb ), +  113-  fragments. In  The  r e s u l t s are g r a p h i c a l l y depicted i n F i g u r e  the presence  o f Ybb~  o r Dp  dramatically increased. data presented  i n Table  1187,  t h e X/0  This i s p a r t i c u l a r l y 6 which  X/0  males d e r i v e d from  is  evident i n the  i n v o l v e s t h e compound-X c h r o -  mosome m a r k e d w i t h y e l l o w and w h i t e . of  viability  7.  The  baseline  viabilities  t h i s compound-X a r e e x t r e m e l y  low.  T h e s e c r o s s e s a r e t h u s t h e most a c c u r a t e gauge o f i n c r e a s e d viability In  due  fragments.  a l l c r o s s e s w h e r e s t a n d a r d X/0  the presence In  to the accessory  of the accessory fragments  elevated  t h o s e m a t i n g s t h a t p r e s e n t m o d e r a t e X/0  heterochromatic u a l s may  e f f e c t was  i s very  low,  viability.  viability,  n o t as pronounced.  the  These  individ-  be l a r g e l y i n s e n s i t i v e t o t h e e x t r a h e t e r o c h r o m a t i n  as t h e i r o r i g i n a l c o n d i t i o n i s n o t may  viability  have c i r c u m v e n t e d  heterochromatin  the problem  s e v e r e l y m u t a n t and a l l e v i a t e d by t h e  i n the other stocks.  The  thus,  excess  heterochromatic  e f f e c t i s c o n s i s t e n t and u n i d i r e c t i o n a l f o r a l l s t o c k s r e gardless of t h e i r The X/0  genotype.  r i b o s o m a l g e n e s may  viability  i n these t e s t s .  exert a positive The  rescue  e f f e c t on  o f t h e X/0  the  viability  by a s t a n d a r d Y-chromosome h a s b e e n p r e v i o u s l y d e s c r i b e d i n this text.  Experiments  utilizing  a Y-chromosome  deficient  i n rRNA c i s t r o n s i n d i c a t e t h a t t h i s f r a g m e n t d r a m a t i c a l l y i n c r e a s e s the v i a b i l i t y viability observed  o f s c u t e X/0  males.  However,  the  o f s c u t e X/Ybb~ m a l e i s c o n s i s t e n t l y l e s s t h a n t h a t f o r the X/Ybb  +  males i n the c o n t r o l  experiments.  114.  T h i s d i f f e r e n c e c o u l d he a s s o c i a t e d w.ith t h e l a c k o f rRNA c i s t r o n s o r some o t h e r f a c t o r i n t h e v i c i n i t y Y bobbed l o c u s .  A s t h i s Ybb~ chromosome was o b t a i n e d  r a d i a t i o n induced occurs not  of the by  b r e a k a g e , one o n l y knows t h a t t h e d e l e t i o n  on t h e s h o r t arm, d e l e t e s t h e r i b o s o m a l  remove a n y o f t h e K  fertility  factors.  g e n e s and d o e s  Cytological pre-  p a r a t i o n s are i n c o n c l u s i v e i n q u a n t i t a t i n g the extent heterochromatic to  deletion.  Although  of the  information pertaining  s p e c i f i c r e g i o n a l d i f f e r e n c e s o n t h e Y-chromosome o f  D. m e l a n o g a s t e r a r e l a c k i n g , H e s s (1968) d e f i n e d r e g i o n s  of  t h e D•  vari-  h y d e i Y-chromosome t h a t h a v e v a r i a b l e e f f e c t s on  egating p o s i t i o n e f f e c t mutants.  This p a r t i c u l a r  i s favored  carries a fully functional  i n t h i s t e x t a s Dp 856  argument  n u c l e o l a r o r g a n i z e r r e g i o n and y e t does n o t e x e r t a  dramatic  e f f e c t o n i n c r e a s i n g t h e X/0  region  i n Dp  856  viability.  The b o b b e d  i s d e r i v e d f r o m a n X-chromosome a n d may n o t be  associated with s i m i l a r f a c t o r s present These r e s u l t s  suggest t h a t there  the bobbed r e g i o n s  on t h e Y-chromosome.  e x i s t s a d i f f e r e n c e between  on t h e Y a n d X-chromosomes.  I t appears  t h a t t h e b o b b e d r e g i o n a s s o c i a t e d w i t h t h e Y-chromosome influence v i a b i l i t y  o f t h e s c u t e X/0  males while  may  t h e X bobbed  region exerts a lesser effect. The s c u t e  d u p l i c a t i o n s present  appear to rescue  on Dp 1337  and Dp  a s i g n i f i c a n t p o r t i o n o f t h e X/0  The r e s u l t s f o r t h e s e  856  males.  d u p l i c a t i o n s c a n be c o m p a r e d t o Dp  w h i c h c a r r i e s s i m i l a r amounts o f h e t e r o c h r o m a t i n  but l a c k s  1187  115.  a f u n c t i o n a l scute l o c u s . mosomes, t h e p r e s e n c e with a v i a b i l i t y  o f t h e e x t r a s c u t e l o c u s was  increase.  i n a c o m p a r i s o n o f Dp r e s p e c t to the  I n a l l non-recombinant scute  T h i s i s most c l e a r l y 1337  II87 and Dp  scute l o c u s .  The  the e x t r a scute l o c u s i s observed sions. i n X/0 The  Scute-V2and scute-8  i n the  illustrated only with  i n f l u e n c e of  scute-8  type  inver-  show a t l e a s t a t w o - f o l d i n c r e a s e  v i a b i l i t y when t h e m a l e s c a r r y a s c u t e  s c u t e - S i type  associated  which d i f f e r  most p r o f o u n d  chro-  duplication.  i n v e r s i o n s show s i m i l a r r e s u l t s b u t n o t  as  pronounced. The t y p e and  r e c o m b i n a n t chromosomes t h a t a r e c r e a t e d f r o m s c u t e - S i scute-8  recombination illustrated  type  c a r r y two  event.  i n these  The  scute l o c i  as a r e s u l t of  e f f e c t s o f t h i s anomaly are  experiments.  well  G a r c i a - B e l l i d o (1979)  has  r e p o r t e d t h a t three doses of the scute r e g i o n decreases bility  i n males.  t o c a r r y two another  One  w o u l d e x p e c t many o f t h e  scute l o c i  and  the donation  The  r e s u l t s presented  recombinants  male  possessing  i n both Table  7 are c o n s i s t e n t w i t h the h y p o t h e s i s a s s o c i a t e d w i t h s c u t e male l e t h a l i t y . two  scute l o c i ,  via-  o f a Dp_ c a r r y i n g  s c u t e l o c u s w o u l d r e s u l t i n an X/Dp  three scute l o c i .  In a l l i n d i v i d u a l s that should  6 and triplocarry  t h e r e i s a marked r e d u c t i o n o f v i a b i l i t y  t h e r e c o m b i n a n t X-chromosome i s a s s o c i a t e d w i t h a Dp These r e s u l t s p r o v i d e f u r t h e r evidence  the  t h a t the  when  sc . +  inviability  a s s o c i a t e d w i t h t h e s c u t e l o c u s d e s c r i b e d by G a r c i a - B e l l i d o i s a f u n d a m e n t a l phenomenon o f t h e  gene.  116.  The  work was  experiment procedure  next extended  to i n c l u d e the  i n v o l v i n g the maternal e f f e c t .  reciprocal  The  experimental  i n v o l v e d m a t i n g homozygous s c u t e f e m a l e s  a t t a c h e d X•Y  to  males c a r r y i n g the chromosomal fragments.  r e s u l t s are presented i n Table  The  8.  Consistent w i t h previous experiments, a c l a s s i c  maternal  e f f e c t i s o b s e r v e d when t h e s c u t e X-chromosome i s i n h e r i t e d from the female.  The  baseline v i a b i l i t i e s  of a l l scute  X/0  m a l e s a r e g r e a t l y i n c r e a s e d as compared t o t h e p r e v i o u s paternal studies.  This reduces  s e n s i t i v i t y to  i n c r e a s e s but a m p l i f i e s response The  to v i a b i l i t y  h e t e r o c h r o m a t i c e f f e c t on v i a b i l i t y  p a t e r n a l e f f e c t experiments appears maternal experiments. n o t e d b e t w e e n t h e X/0  viability  differences  1187).  I t i s apparent  s u p p r e s s i o n o f t h e X/0  that the •  l e t h a l i t y masks t h e  identified.  to those observed i n the p a t e r n a l  experiments.  m a j o r f a c t o r i n f l u e n c i n g an i n c r e a s e o f v i a b i l i t y  presence  o f a s t a n d a r d Y-chromosome b o b b e d r e g i o n .  i t y t o any  significant  experiments, i t appears viability  and  extent.  A s was  observed  was  the  However,  t h e X - c h r o m o s o m a l b o b b e d r e g i o n d i d n o t a l t e r t h e X/0  X/0  i n the  e f f e c t s o f t h e bobbed r e g i o n s a r e s i m i l a r i n t h i s  experiment The  observed  m a l e s and t h o s e m a l e s c a r r y i n g s u r p l u s  heterochromatic effect previously The  decreases.  t o be o b s c u r e d i n t h e  There are l i t t l e  h e t e r o c h r o m a t i n ( Y b b ~ , Dp maternal effect  viability  viabil-  i n the previous'  t h a t the Y bobbed r e g i o n i n f l u e n c e s  i s independent  o f t h e mechanism o f t h e mater-  TABLE 8 A l t e r a t i o n o f M a t e r n a l E f f e c t "by D u p l i c a t i o n s a n d A l t e r e d Y's  0  Y  Ybb  Dp 1187 s c " N0~  Sex Ratio sc sc sc  SI  L8 8 ^+  sc  N  Sex Ratio  N  , Sex Ratio  N  sc Sex Ratio  1337 NO"  N  Dp +  sc Sex Ratio  856 N0  +  N  0.42  9438  0.97  1628  0.47  783  0.38  621  0.53  694  0.59  709  m  0.33  1106  O.87  938  640  O.38  765  0.42  843  1924  1 .22  916  498  1.09  517 830  0.42  1.17  0.35 1 .05  1 .20  746  1.13  521  1.28  2466  1.34  1138  1.17  622  789  1.24  490  1.18  562  1.18  2914  1 .20  1262  1.20  816  1-35 1.11  753  1.17  685  1.06  811  0.99  1238  1 .06  934  1 .06  776  1.03  483  1-.12  627  1.22  736  0.58  658  0.46  608  0.80  539  0.67  666  V2 sc  Sex Ratio  +  „ yB  + dl49  8  N  Dp  4  sc S1L  8R  0.88  3746  1 .04 1842  0.82  553  1 .01  S1L  V2R  1.05  1230  1.12  1119  1 .00  590  0.94  919 660  L8L  8R  O.92  992  1316  0.86  671  0.60  589  0.38  823  V2R  1.03  1008  454  1.08  925  0.19  730  0.46  586  V2L  8R  1.06  1314  1.14  1057 922  0.99 0.92  806  L8L  0.97 1.26  0.85  618  0.99  841  0.92  460  1.14  591  8L V2R  0.83  1136  840  0.90  904  0.85  703  O.76  625  O.96  651  4L V2R  0.81  1152  0-93 1.08  929  0.93  560  0.84  650  0.58  656  0.50  571  ( X-Y/Dp  x  118.  FIGURE 8  E f f e c t o f Ybb~, locus,  and  heterochromatic  the v i a b i l i t y  II  :  an a d d i t i o n a l  Maternal  duplications  o f s c u t e X/0  inheritance  scute on  males.  of scute  inversion  119.  S1 SC  8  D  y  B Bars represent:  X/0,  Dp  1187  ( s c b b ) , Dp _  S1L  sc + dl 49 _  1337  ( l e f t to  ( s c b b ) , Dp +  -  8R  right) 856  (sc bb ), Y +  +  bb . _  120.  effect. The  e l e v a t e d b a s e l i n e v a l u e s f o r s c u t e X/0  the maternal the l e t h a l i t y All  experiments  provides a sensitive  a s s o c i a t e d w i t h -three s c u t e l o c i  of the scute recombinants  f e s t a dramatic  c a r r y i n g two  reduction i n v i a b i l i t y  d u p l i c a t i o n f o r the  scute l o c u s .  viability  system to  in  test  i n a male.  scute l o c i  mani-  i n association with  This i s consistent with  p r e v i o u s s t u d i e s i n t h i s t h e s i s and w i t h s t u d i e s c o m p l e t e d other authors data suggest  ( G a r c i a - B e l l i d o and  effect.  observed  1978).  by  The indepengene  r e d u c t i o n beyond the b a s e l i n e  e s t a b l i s h e d f o r s c u t e X/0 i n both maternal  is  Three doses of the scute  i n a male r e s u l t s i n a v i a b i l i t y viability  Santamaria,  t h a t the t r i p l o - s c u t e male l e t h a l i t y  dent of t h e maternal  a  males.  and p a t e r n a l  This effect i s  experiments.  121 .  - Chapter 5 The  The the  original  Compound-X E f f e c t  studies i n t h i s research area involved  m a t i n g o f s c u t e m a l e s t o compound-X f e m a l e s t h a t  a f r e e Y-chromosome.  I n the c o n t r o l s , t h i s female  a m a r k e d Y-chromosome t h a t c o u l d be i d e n t i f i e d male.  The  first  compound-X u t i l i z e d was  carried  carried  i n the scute  C(1 ).RM y w/0  and  r e s u l t s o b t a i n e d from these c r o s s e s correspond w e l l w i t h r e s u l t s p u b l i s h e d by B a k e r compound-X o r one  ( 1 9 7 2 ) who  s i m i l a r l y marked.  e i t h e r used t h i s  When t h e y w f e m a l e  c a r r i e d i n a s t o c k w i t h a f r e e Y-chromosome, i t was difficult of  same  extremely  t o m a i n t a i n a pure b r e e d i n g s t o c k as a breakdown  t h e compound-X o c c u r r e d f r e q u e n t l y .  I t was  decided that  a n o t h e r compound-X t h a t w o u l d n o t b r e a k down c o u l d be for  was  the experiments.  used  C r o s s e s were c o n d u c t e d , t h e r e f o r e ,  with  f e m a l e s c a r r y i n g C ( l ) R M Y E n y / 0 , a compound-X_which d i d n o t s  b r e a k down a p p r e c i a b l y i n t h e p r e s e n c e o f a Y-chromosome. was  a s u r p r i s i n g o b s e r v a t i o n to note t h a t the  viabilities  d e t e r m i n e d for: t h e s e e x p e r i m e n t s d e v i a t e d s i g n i f i c a n t l y the  p r e v i o u s e x p e r i m e n t s u s i n g C(1)RM y w/0  was  the f i r s t  females.  from  This  i n d i c a t i o n that l e t h a l i t y a s s o c i a t e d w i t h the  p a t e r n a l e f f e c t was nal  It  chromosomal  c o n d i t i o n a l t o some e x t e n t on t h e m a t e r -  constitution.  T a b l e 9 and F i g u r e 9 p r e s e n t d a t a a c c u m u l a t e d f r o m t h e m a t i n g s o f n u m e r o u s d i f f e r e n t compound-X f e m a l e s t o m a l e s  TABLE 9 The Compound-X E f f e c t yw Sex Ratio  +_ N  Sex Ratio  yvbb N  Sex Ratio  yvpn N  Sex Ratio  Y Eny N  Sex Ratio  N  +S  0.04  2004  0.03  I896  0.04  1512  0.06  1931  0.06  1644  +dl4-9  0.00  1809  0.00  1480  0.00  836  0.00  918  0.00  1009  0.03  2138  0.07  963  0.04  751  0.15  824  0.12  780  0.04  1610  0.03  1168  0.05  916  0.10  659  0.12  1138  0.01  1859  0.04  728  0.03  704  0.07  1326  0.10  956  0.11  2565  Q.12  1269  0.16  1017  0.26  1157  0.23  1068  0.09  2616  0.08  1352  0.12  696  0.26  922  0.24  788  0.29  2371  .0.26  1619  0.23  754  0.39  699  0.46  1041  sc  0.86  2893  0.87  1052  0.95  589  0.89  710  0.99  1164  S I L 8R  0.09  1935  0.18  1736  0.16  653  0.26  2067  O.31  1436  SIL  L8R  0.40  1042  0.47  924  0.43  718  0.51  831  0.63  862  S I L V2R  0.79  1610  0.76  836  0.81  830  0.80  750  O.87  904-  L 8 L 8R  0.08  1319  0.06  1124  0.11  919  0.16  690  0.19  886  8L V2R  0.05.  1213  0.11  830  0.14  681  0.17  928  0.22  749  V 2 L 8R  0.09  1066  0.20  765  0.16  738  0.16  826  0.20  915  4L V2R  0.26  1059  0.44  911  0.35  926  0.37  926  0.44  681  sc sc  S 1  S 1  SI sc sc sc sc sc  ym  L8  3  sn^  L8  m + dl49  8  8 ^  +  V2 sc  123.  FIGURE 9  The Com-pound-X  Effect  124.  40  30  sex ratio  20  10  S1 SC  „ y B  sc  L8  m  Bars represent: C ( l ) RM y w,  sc  8  S1L  (left to right)  C ( l ) RM y v b b ,  C ( l ) RM Y E n y s  8R  125-  hemizygous f o r t h e v a r i o u s s c u t e i n v e r s i o n chromosomes.  The  d a t a i n T a b l e 9 a r e o r g a n i z e d from l e f t t o r i g h t on t h e b a s i s o f -the s e v e r i t y o f l e t h a l i t y .  O f t e n , d i f f e r e n c e s between ad-  j a c e n t s e t s o f d a t a a r e n o t s i g n i f i c a n t l y d i f f e r e n t but d a t a compared a t any g r e a t e r d i s t a n c e always d i f f e r I t i s apparent t h a t autosomal  significantly.  modifying f a c t o r s are not r e -  s p o n s i b l e f o r t h i s d i f f e r e n c e as t h e compound-X s t o c k s were back c r o s s e d numerous t i m e s t o males from t h e same X•Y/O s t r a i n t o randomize such  effects.  I t seems l i k e l y t h a t t h e X/0 v i a b i l i t y i s s e n s i t i v e t o t h e m a t e r n a l chromosomal c o n s t i t u t i o n o r t h e m a t e r n a l b u t i o n t o the zygote.  contri-  I t i s unfortunate that the heterochro-  m a t i c c o n s t i t u t i o n o f t h e s e d i f f e r e n t compounds has n o t been c a r e f u l l y analyzed.  I t i s p o s s i b l e that the v i a b i l i t y  dif-  f e r e n c e s may r e f l e c t t h e h e t e r o c h r o m a t i c c o n t e n t i n t h e matern a l genome.  The e v i d e n c e s u p p o r t i n g t h i s h y p o t h e s i s i s l i m -  i t e d and i n v o l v e s t h e i n c r e a s e d X/0 v i a b i l i t y observed i n compound-X chromosomes t h a t c a r r y e x t r a Y-chromosomal h e t e r o chromatin.  S i m i l a r experiments were performed  with respect  t o a v a r i e t y o f X•Y chromosomes and t h e m a t e r n a l d o n a t i o n o f the s c u t e X-chromosome.  The r e s u l t s i n d i c a t e t h a t t h e v i a -  b i l i t y m o d i f i c a t i o n i s c o n f i n e d t o d i f f e r e n c e s w i t h i n t h e mat e r n a l genome.  S i g n i f i c a n t d i f f e r e n c e s c o u l d n o t be shown  between v i a b i l i t i e s produced  by any o f t h e X•Y chromosomes.  The c h a r a c t e r i z a t i o n o f t h e h e t e r o c h r o m a t i c c o n t e n t o f these chromosomes i s i n c o m p l e t e and l i t t l e i s known c o n c e r n i n g t h e  126.  r e l a t i v e p r o p o r t i o n s o f X and Y-chromosomal  heterochromatin.  T h i s "being t h e c a s e , one c a n n o t i n f e r a n a s s o c i a t i o n b e t w e e n the heterochromatic  c o n t e n t i n t h e g a m e t e s and X/0  T h e r e a p p e a r s t o be a v e r y s i g n i f i c a n t ability  associated with the maternal  viability.  viability-modifying  genome b u t a n y p r o p o s a l s  o f m e c h a n i s m s w o u l d be p u r e l y s p e c u l a t i v e .  127.  - Chapter 6 The  Temperature  Temperature  Effect  i s a c l a s s i c modifier of p o s i t i o n - e f f e c t  v a r i e g a t i o n and i t i s o f i n t e r e s t t o o b s e r v e i f t h e x/0 thality  observed w i t h the scute  this variation. temperature  The  at  inversions i s subject to  b r i s t l e phenotype  h a s b e e n shown t o be  s e n s i t i v e b u t h a s a l s o b e e n shown t o be  of v a r i e g a t i n g systems.  The  scute phenotype  r e d u c e d t e m p e r a t u r e s (14-°, 18°C)  is  I v e s , 1938;  i n accord  G e r s h , 1949;  w i t h most v a r i e g a t i n g systems where  l e t h a l i t y was  1934, This  reduced  elevated  tem-  I f the scute  X/0  a f u n c t i o n o f a scute v a r i e g a t i n g system  one  w o u l d p r e d i c t t h a t X/0 temperatures.  extreme  Furman e t a l . , 1 9 7 9 ) -  p r o m o t e a more w i l d p h e n o t y p e .  v i a b i l i t y w o u l d be r e d u c e d a t d e c r e a s e d  Should l e t h a l i t y  o f rRNA p r o d u c t i o n viabilities  i s more  27°C ( C h i l d ,  t e m p e r a t u r e s f a v o r t h e m u t a n t e x p r e s s i o n and peratures  atypical  and becomes i n c r e a s i n g l y  w i l d type as the t e m p e r a t u r e s approach 1940;  le-  be a s s o c i a t e d w i t h  or processing,  one w o u l d p r e d i c t e l e v a t e d  a t l o w e r t e m p e r a t u r e s owing  m e n t a l t i m e and a c c o m o d a t i o n  problems  to increased  develop-  t o the mutant s i t u a t i o n .  The  d e f i n i t i o n of a temperature e f f e c t could p o s s i b l y d i s c r i m i n a t e b e t w e e n t h e s e two  possibilities.  T a b l e 10 f u r n i s h e s d a t a c o n c e r n e d w i t h t h e p a t e r n a l e f f e c t d e r i v e d a t 18°, carried  25°  and  29°C.  T h e s e e x p e r i m e n t s were  out u s i n g the f o l l o w i n g p r o t o c o l .  Two  females  and  128.  TABLE 10  The P a t e r n a l T e m p e r a t u r e  18° C Sex Ratio  Effect  29 °C  .25 °C N  Sex Ratio  N  Sex Ratio  I  0.02  843  0.05  1361  0.05  1265  0.00  638  0.04  1042  0.03  1127  0.12  652  0.23  956  0.29  1044  0.15  562  0.31  0.26  908  V2  0.21  717  0.37  837 1106  0.45  1072  4  0.77  O.83  950  0.88  1046  0.05  659 604  0.11  0.10  994  vincy  0.07  678  0.18  1053 1102  0.15  1078  L8L  8R  0.06  806  0.13 • 1153  0.19  1126  V2L  8R  0.18  591  0.22  916  0.29  1092  V2R  0.02  629  0.13  1005  0.15  1135  sc sc sc  sc sc  +S  S 1  L8  m  8 ^+ + dl49  8  sc Base  8L  yB  ( sc A  x  C(1)RM y v p n / 0  )  129.  FIGURE 10  The T e m p e r a t u r e  I  :  Paternally  Effect  inherited  X-chromosome  130.  40  30  sex ratio  20  10  S1 SC  0  y  B  sc  L8  m  Bars represent:  sc  8  (left to right)  18°C, 25°C, 29°C  S1L 8 R  131  two  •  m a l e s were mated i n a s i n g l e s h e l l  were a l l o w e d  t o l a y eggs a t t h i s  29°  f o r a f u r t h e r 2 days.  t h a t the  desired  vials  t r a n s f e r e d to f r e s h v i a l s  p r o g e n y were d e r i v e d and  and  and  does not  allowed  Parents  to l a y  from a g e n e t i c a l l y i d e n t i c a l were e n t i r e l y  seem t o be p r o f o u n d when t h e father.  T h e r e i s no  between v i a b i l i t i e s at 25° w i t h the  between 25°  at  the  population at  the  and  29°.  t h o s e r a i s e d a t 18° a t 18°  X-chromosome i s  consistent  and  this  difference  i s also  T h e r e a p p e a r s t o be  i n terms of v i a b i l i t y .  hypothesis  improper expression  of the  c a s e s w h e r e v i a b i l i t y was  X/0  scute  increased  locus. at the  t u r e which i s c o n t r a d i c t o r y to the n o t i o n o f rRNA g e n e s a r e  a f f e c t e d by p o s i t i o n  temperature e f f e c t associated  These  lethality  difand  increased  w i t h a more s e v e r e  support the  scute  phenotype  or 25°  The  r e d u c e d b r i s t l e number p h e n o t y p e . that  differ-  a consistent  f l i e s r a i s e d e i t h e r at 29°  i s also associated  compatible  T h e r e a r e no  s i o n of the  The  lethality  i n terms of the mutant b r i s t l e  between the  thality  or 29°  scute  observed b r i s t l e phenotypes.  ences d e t e c t a b l e  ference  w i t h X/0  temperature e f f e c t associated  d o n a t e d by t h e  no  immediately  This p r o t o c o l ensured t h a t  developmental periods  The  temperature.  The  of the  They  e n v i r o n m e n t t o l a y eggs f o r 2 d a y s .  i n an 18°  were a g a i n  •  temperature f o r 3 days.  p a r e n t s w e r e t h e n t r a n s f e r r e d t o new placed  25  vial•at  is a  expresdata function  There were lower  t h a t the  temperaexpression  effect. with  le-  the  maternal  132.  experiments omenon.  i n d i c a t e s a more p r e c i s e d e f i n i t i o n o f t h e p h e n -  These d a t a a r e p r o v i d e d i n T a b l e  11.  The m o s t  stri-  k i n g observation i s the r e d u c t i o n of the maternal e f f e c t at 18°. is  I n every experiment  s i g n i f i c a n t l y reduced.  e x c e p t f o r s c u t e - 4 , t h e X/0 Phenotypically,  one c a n n o t  viability distin-  g u i s h a d i f f e r e n c e b e t w e e n t h e X/0 m a l e s g e n e r a t e d a t t h e three temperatures.  This i s l i k e l y  a r e s u l t of the maternal  s u p p r e s s i o n o f t h e s e v e r e s c u t e e x p r e s s i o n s t h a t has been cussed p r e v i o u s l y . viability  The t e m p e r a t u r e  e f f e c t r e d u c t i o n o f X/0  a t l o w e r t e m p e r a t u r e s a p p e a r s t o be a n o t h e r g e n e r a l  phenomenon a s s o c i a t e d w i t h t h e s c u t e i n v e r s i o n s . t i o n i s observed and  dis-  i n b o t h m a t e r n a l and p a t e r n a l  T h i s reducexperiments  seems t o be a s s o c i a t e d w i t h t h e p h e n o t y p i c e x p r e s s i o n o f  the scute phenotype.  Thus, t h e experiments  d e f i n i n g a temperature have produced inviability  involved with  e f f e c t a s s o c i a t e d w i t h t h e X/0  another l i n e  lethality  of evidence suggesting that the  i s p r i m a r i l y a f u n c t i o n of the v a r i e g a t e d expres-  s i o n o f t h e s c u t e gene.  133-  TABLE 11  The M a t e r n a l T e m p e r a t u r e  29°C  25°C  18° C Sex Ratio  Effect  Sex Ratio  N  N  Sex Ratio  I 1008  862  0.35 0.23  904  1.08  836  683  0.99 1.10  781  1.02  901  0.70  720  0.94  IO36  0.89  998  O.96  0.91  1103  0.87  0.75  783 661  0.88  811  1.13  940  vincy  0.69  594  1.03  1.07  812  L8L 8R  O.63  554  0.81  739 836  0.88  843  V 2 L 8R  0-77  691  930  0.93  890  8L  0.79  805  0.95 0.90  1068  0.84  1022  sc sc  +S yB  0.19  765  O.36  947  m  0.09  538  0.29  +  0.78  641  + dl49  0.83  V2  4  S 1  L8  sc  8  sc  8  sc  sc Base  V2R  ( sc /sc X  X  x  X-Y/O )  814  1216  134.  FIGURE 11  The T e m p e r a t u r e  II  :  Effect  Maternally inherited  X-chromosome  135-  no  100  90  80  I  70  sex atio  60  r  50  40  30  y  20  to  y  sc  L8  m  Bars represent:  sc  8  ( l e f t to right)  1 8 ° C , 25°C, 29°C  S1L  136.  - Chapter 7  -  The D e v e l o p m e n t a l  One scute X/0 ment.  o f t h e most p r o m i n e n t  Delay  features associated with  c o n d i t i o n has been the extended p e r i o d o f d e v e l o p -  T h i s has been e s t a b l i s h e d as a n o t h e r of the  phenomena a s s o c i a t e d w i t h t h e s c u t e i n v e r s i o n s . is  the  peculiar  The  delay  o b s e r v e d i n b o t h m a t e r n a l and p a t e r n a l e x p e r i m e n t s  has been v e r y c a r e f u l l y examined as a r e s u l t o f the mental design.  and  experi-  T h i s anomaly has been o b s e r v e d i n p r e v i o u s  w o r k s and t h e a u t h o r s s u g g e s t t h a t t h e d e l a y r e p r e s e n t s a d i s f u n c t i o n o f t h e e x p r e s s i o n o f t h e rRNA g e n e s ( N i x , 1 9 7 3 ; Baker, 1 9 7 1 ) opmental  These a u t h o r s a l s o a l l u d e t o a s i m i l a r  delay associated with f l i e s  deficient  i n rRNA  O t h e r a u t h o r s have s u g g e s t e d t h a t t h i s r e t a r d e d a l l o w s f o r compensation  development  I t i s a significant  v a t i o n t h a t t h e d e v e l o p m e n t a l d e l a y was  shown t o be  r e l a t e d t o t h e s e v e r i t y o f t h e bobbed phenotype.  The  of  t h e s e e x p e r i m e n t s i s t o examine t h e d e v e l o p m e n t a l  of  the scute mutants  a n d compare t h e s e r e s u l t s w i t h  d a t a c o l l e c t e d f r o m rDNA d e f i c i e n t  specific  the purposes  obser-  directly purpose profiles similar  individuals.  of t h i s d i s c u s s i o n , the r e s u l t s of .  experiments w i l l  e r e d t o be e x e m p l a r y  genes.  o f c e l l u l a r rRNA c o n t e n t (Mohan and  R i t o s s a , 1 9 7 0 ; Malva et a l , 1 9 7 9 ) .  For  devel-  be i l l u s t r a t e d  o f t h e phenomenon.  as t h e y are The  n u m e r o u s s c u t e i n v e r s i o n s and b o b b e d m u t a n t s  consid-  data f o r the are presented i n  137-  T a b l e 12.  R e p r e s e n t a t i v e g r a p h i c f i g u r e s of the data are  d e p i c t e d i n F i g u r e s 12 t h r o u g h  14.  From t h e s e d a t a , i t i s a p p a r e n t t h a t t h e r e i s a  consid-  erable developmental delay a s s o c i a t e d w i t h the scute condition.  The  only i n v e r s i o n d e p a r t i n g from t h i s  X/0  generali-  z a t i o n i s s c u t e - 4 w h i c h has p r e v i o u s l y been c h a r a c t e r i z e d a t y p i c a l o f t h e numerous s c u t e r e a r r a n g e m e n t s .  The  control  s i t u a t i o n s i n d i c a t e t h a t the r e t a r d e d development can largely The  as  be  s u p p r e s s e d i n t h e p r e s e n c e o f a Y-chromosome. r e s u l t s d e p i c t e d i n T a b l e 12  o f t h e t i m e r e q u i r e d t o r e c o v e r 50$  are expressed i n terms  of males or females.  -  The  d i f f e r e n c e b e t w e e n t h e s e two v a l u e s i s d e f i n e d a s t h e d e v e l o p m e n t a l d e l a y ( s e e F i g u r e 13)i n t h e X/0 a Ybb  The  bb X-chromosomes a r e  lethal  s i t u a t i o n and t h e r e f o r e t h e y w e r e r e c o v e r e d w i t h  chromosome.  The X b b - l e t h a l / Y b b p h e n o t y p e i s a s e v e r e  bobbed c o n d i t i o n w i t h f r e q u e n t abdominal able developmental delay.  The  e t c h i n g and a n o t i c e -  bb m a t e r n a l e f f e c t  experiments  w e r e c o m p l e t e d by c r o s s i n g h e t e r o z y g o u s d l 4 9 / b b - l e t h a l  females  t o X•Y/Ybb m a l e s .  exper-  The  developmental p r o f i l e s i n these  i m e n t s t h u s compare t h e bb/Ybb m a l e s t o t h e d l 4 9 / Y b b and t h e h e t e r o z y g o u s  males  females.  When t h e s c u t e X i s p a t e r n a l l y i n h e r i t e d , t h e d e v e l o p m e n t a l d e l a y a p p e a r s t o be b e t w e e n two of the i n v e r s i o n s studied. b o b b e d chromosomes was  one  The day.  and t h r e e d a y s f o r m o s t  delay associated with The  the  c o n t r o l v a l u e s f o r the  scute i n v e r s i o n s i n d i c a t e that the developmental delay i s  138.  TABLE The  12  Developmental  Delay  PATERNAL  MATERNAL  Female  Male  Delay  Female  Male  Delay  m control  13 .0 12 .6  15- 7 13- 7  2•7 1 .1  12 • 9 13 • 3  14. 9 14. 1  2.,0 0.,8  +S yB control  13 • 3 13 • 5  15- 6 14. 3  2• 3 0 .8  13 .4 12 .8  14. 7 13- 5  1 .• 3 0,• 7  ym control  12 • 7 13 • 3  15- 6 13- 8  2• 9 0• 5  13 .2 12 • 3  15. 0 12. 7  1,,8 0..4  +dl4-9 control  12 .6  15- 2 14. 8  2 .6 0• 9  12 .0 13 .2  12. 8  13 • 9  13- 5  0,.8 0,• 3  12 .0 12 .8  14. 4 13- 2  2 .4 0 .4-  12 • 3 12 .8  13. 6 13- 1  1,• 3 0,• 3  12 .8 12 • 3  13- 7 12. 5  0• 9 0 .2  12 • 5 12 .1  13- 3  0,.8 0..1  control  12 • 7 12 .2  12. 9 12. 4  0 .2 0 .2  13 .1 13 • 3  12. 9 13- 3  -0,.2 0 .0  asc control  13 .2 13 .6  15- 7 13. 6  2• 5 0 .0  12 .2 12 .8  14. 0 12. 8  1 .8 0 .0  control  12, .8 13. • 3  14-.,0  1, .2 0, •2  13. ,4 13. ,0  14 .8  13- • 5  12 • 9  1, .4 -0, .1  13. .0 12, -9  13. ,8 12, • 7  0, .8 -0, .2  12, -5 13. • 3  13 .6 13 • 5  1, .1 0, .2  sc sc sc sc  S 1  SI  8  8 ^ sc + control V2 sc c o n t r o l 4-  sc  bb 4-52 * control 1  12. 1  These numbers r e p r e s e n t days e l a p s e d between r e m o v a l and r e c o v e r y o f 50% o f t h e r e s p e c t i v e c l a s s . *  of  adults  I t was n e c e s s a r y t o r e c o v e r t h e s e g e n o t y p e s w i t h a Ybb chromosome. The m a t e r n a l e x p e r i m e n t s i n v o l v e d f e m a l e s h e t e r o z y g o u s f o r t h e bb chromosome m a t e d t o X•Y/Ybb m a l e s .  139.  FIGURE 12  The D e v e l o p m e n t a l  I  :  Raw  data  Delay  140.  +dl49/B Y  sc  S  Progeny Recovered Day  Female  Male  x  C(1)RM yw/O  Cumulative % Female  Male  0  0  0.00  0.00  0  2.74  0.00  11  53 286  0  17.52  0.00  12  314  3  33-75  0.82  13  604  18  64.96  5-71  14  206  75.61  16.31  15  270  39 107  89.56  45.39  16  102  94.83  64.68  17  98.60  93-48  18  73 21  71 ' 106 7  95-38  19  6  20  0  13 4  99.69 100.00  1935  368  9 10  Total  98.91 100.00  FIGURE  13  The D e v e l o p m e n t a l  Delay  Cumulative percentage recovery a)  sc A  X  C(1)RM  yw/O  b)  sc /Y  X  C(1)RM  yw/Y  c)  sc  8// s c 8  X  X-Y/O  d)  sc  8/ s c 8  X  X-Y/Y  8  8  y  female progeny - s o l i d  line  male progeny - broken l i n e  plots  142.  Day of e c l o s i o n  144.  Day of e c l o s i o n  145.  D s c / sc  + dl 49  8  X-Y/  Y  Cumulative  Recovery 100  8  9  10  11  12  13  14  Day of e c l o s i o n  15  16  17  18  19  20  146.  FIGURE 14  The D e v e l o p m e n t a l  III  :  Probits analysis  a)  s c  8  b)  s c  8  c) d)  Delay  of data  / Y  X  C(1)RM  yw/O  / Y  X  C(1)RM y w / Y  sc / s c  X  X - Y / O  8/ 8 sc / s c  X  X - Y / Y  147.  days  148.  Cumulative  .999 .998 .995 .99 .975 .95 .90  /  .85  <>  • ••  .80 .75 70  /.< f • •• • •  .60  /  .50 .40  /  >  m  • • •  .15  • •• • • •  t  jf  .25 .20  >  ••  •  ( >••  •  • <>  .05  • • • • •  .025 <  .01  8  9  • •  ... — r  »  10  11  12  13  14  days  15  16  17  18  19  20  149.  days  150.  days  151 •  g r e a t l y reduced X/Y  i n t h e s c u t e X/Y  c o n t r o l males s t i l l  t h a t t h e r e may  males.  I n most c a s e s , t h e  e x h i b i t e d a d e l a y and  this  be a n i n h e r e n t d e v e l o p m e n t a l p r o b l e m  w i t h the severe scute mutants.  was in  194-0) .  ( R a f f e l and M u l l e r ,  The  T h i s would  Y-chromosome c a r r i e s a f u l l The  maternal effect  been  scute-Si  developmental  e s s e n t i a l l y e l i m i n a t e d by t h e p r e s e n c e t h e bobbed e x p e r i m e n t s .  associated  T h i s o b s e r v a t i o n has  p r e v i o u s l y r e p o r t e d f o r b o t h t h e s c u t e - L 8 and sions  indicates  be  delay  o f a Y-chromosome expected as  complement o f r i b o s o m a l  e x p e r i m e n t s showed v e r y  t r e n d s i n d e l a y a l t h o u g h t h e X/0 less developmentally retarded.  m a l e s were The  c a t e t h a t t h e m a t e r n a l l y d e r i v e d X/0  inver-  the  genes.  similar  significantly  control  experiments  males r e q u i r e a  indi-  consid-  e r a b l y l o n g e r d e v e l o p m e n t a l p e r i o d t h a n do m a t e r n a l l y d e r i v e d X/Y  males.  The  comparison  p a t e r n a l l y d e r i v e d X/0  of developmental  by t h e mutant c o n d i t i o n . inherited  between  m a l e s and m a t e r n a l l y d e r i v e d  males r e v e a l s t h a t the former group  ternally  rates  X/0  i s more s e v e r e l y  I n g e n e r a l , t h e X/0  affected  f l i e s w i t h pa-  s c u t e X-chromosomes e c l o s e a f u l l  day  l a t e r than g e n e t i c a l l y  i d e n t i c a l males w i t h a m a t e r n a l l y i n -  h e r i t e d X-chromosome.  The m a t e r n a l e f f e c t c o n t r o l  provide f u r t h e r proof that a developmental w i t h the severe scute e x p r e s s i o n s . and  scute-Si  presence The  both e x h i b i t e d  The  experiments  delay i s associated  inversions  scute-L8  s i g n i f i c a n t d e l a y s even i n the  o f a Y-chromosome. b o b b e d e x p e r i m e n t s do n o t i n d i c a t e a  difference  152.  r e s u l t i n g from the p a r e n t a l delay and  a p p e a r s t o he  s o u r c e o f t h e bb  chromosome.  c o n s i s t e n t l y i n t h e r a n g e o f one  a h a l f days whether the  p a t e r n a l l y or maternally.  The  to  one  b o b b e d chromosome i s i n h e r i t e d Phenotypically,  the  bb/Ybb m a l e s  r e c o v e r e d f r o m t h e m a t e r n a l e x p e r i m e n t s were i n d i s t i n g u i s h a b l e from the males r e c o v e r e d i n the p a t e r n a l  experiments.  e x h i b i t e d a s e v e r e l y b o b b e d b r i s t l e p a t t e r n and e t c h i n g was ribosomal  a frequent  observation.  d e f i c i e n t phenotypes are  T h e r e w e r e two  independent of the f o r the  scute  been p r e v i o u s l y c h a r a c t e r i z e d  other  inversions.  severely no  The as  as o b s e r v e d w i t h  inversions.  s m a l l and  The may  delay  with  version  compared t o c o n t r o l s but the previous  observed i n the  r e s u l t from simple  the  not  inversions.  males as  There i s source  of  control situations i s  sampling e r r o r . hypothesis  a mildly affected representative  that  These  data  scute-V2  of the  scute  in-  defects.  Scute-4 i s not t h e X/0  mild  d e v e l o p m e n t o f s c u t e - V 2 x/0  e n t i r e l y c o n s i s t e n t w i t h the  represents  not  condition.  apparent d i f f e r e n c e a t t r i b u t a b l e to the p a r e n t a l  scute-V2.  are  retarded  maternal  as m a n i f e s t i n g  o f t h e n u m e r o u s phenomena a s s o c i a t e d  a p p e a r s t o be  these  i n v e r s i o n chromosomes t h a t d i d  expressions scute  that  d e l a y e d d e v e l o p m e n t i n t h e x/0  exhibit profoundly S c u t e - V 2 has  scute  abdominal  I t i s evident  e f f e c t s t h a t have been c h a r a c t e r i z e d  They  condition.  moderately scute  and  associated  with  significant lethality  Phenotypically,  these i n d i v i d u a l s are  r a r e l y achaete.  In these  in  developmental  153-  experiments,  scute-4 d i d not  e x h i b i t an a p p r e c i a b l e  m e n t a l d e l a y e i t h e r i n t h e X/0  o r t h e X/Y  condition.  been p r e v i o u s l y observed  t h a t s c u t e - 4 shows l i t t l e  change between t h e s e  c o n d i t i o n s w h i c h may  the  two  s c u t e e x p r e s s i o n i n s c u t e - 4 may  it  It  has  phenotypic  indicate  that  a r i s e f r o m a t r u e muta-  t i o n r a t h e r than a v a r i e g a t i n g expression. supported  develop-  This theory i s  by t h e u n i f o r m p h e n o t y p e p r e s e n t e d  by  s c u t e - 4 when  i s subjected to c l a s s i c a l m o d i f i e r s of p o s i t i o n  effect  variegation. A l t e r n a t e l y , t h e v a r i e g a t e d e x p r e s s i o n o f s c u t e may r a d i c a l l y d i f f e r e n t owing to the chromatin  specific  i n f l u e n c i n g t h e s c u t e gene.  i a l l y plausible i n light  blocks of heterochromatin.  This theory i s  of the c l a s s i c  inversions (sc , s c ^ ,  sc^)  matin.  o f s c u t e - V 2 a p p e a r s t o be  The  breakpoint  are i n the proximal  d l e o f t h e rDNA gene c l u s t e r and f u r t h e r study specific  elsewhere.  developmental  espec-  this  the  sequences i n the l a r g e  Scute-4 i s broken i n the  w h i l e the breaks  8  hetero-  of recent research concerning  non-random d i s t r i b u t i o n o f s a t e l l i t e  X heterochromatin  region of  be  distal  scute heterochroi n the  mid-  special feature merits  I t r e m a i n s t o be  seen whether  the  d e l a y s a s s o c i a t e d w i t h the scute i n -  v e r s i o n s are c o r r e l a t e d w i t h d i s t i n c t i v e r e g i o n s of  hetero-  chromatin. The  purpose of examining  bobbed l e t h a l phenomenon and  i n d i v i d u a l s was  the developmental to determine  d e l a y i n the  the extent of  this  t o c o r r e l a t e the d e l a y w i t h the bobbed pheno-  154.  type.  I n a l l e x p e r i m e n t s , t h e Xbb'VYbb i n d i v i d u a l s w e r e p h e n -  otypically  s e v e r e l y bobbed.  The d e l a y o b s e r v e d was a p p r o x i -  m a t e l y one d a y a n d t h i s e f f e c t was e l i m i n a t e d i n t h e p r e s e n c e o f a Y-chromosome.  The d e v e l o p m e n t a l d e l a y a s s o c i a t e d  a s e v e r e bobbed c o n d i t i o n i s t h u s q u a n t i f i e d .  with  Comparing the  d e v e l o p m e n t a l r e s u l t s between t h e bobbed i n d i v i d u a l s and t h e scute i n d i v i d u a l s i t i s apparent that the delay a s s o c i a t e d w i t h t h e s c u t e mutant i s c o n s i d e r a b l y l o n g e r .  Also, the  s c u t e X/0 m a l e s a r e n o t a s s o c i a t e d w i t h a b o b b e d  phenotype  o f any k i n d . These -experiments have e s t a b l i s h e d t h e f o l l o w i n g  lines  of evidence suggesting that the developmental delay i s not a r e s u l t o f rDNA d i s f u n c t i o n . s i t u a t i o n although a f u l l There  The d e l a y i s e v i d e n t i n t h e X/Y  c o m p l e m e n t o f rDNA i s p r e s e n t .  i s a d i f f e r e n c e i n d e v e l o p m e n t a l t i m e w h i c h i s depen-  dent upon t h e p a r e n t a l  source of i n v e r s i o n .  The  developmental  r e t a r d a t i o n associated w i t h the scute rearrangements l e n g t h y than t h a t accompanying  t h e bobbed mutants.  o f d e l a y o b s e r v e d f o r t h e bobbed mutants produce  a s e v e r e bobbed phenotype  identified  i n t h e s c u t e X/0 m a l e s .  i s more The p e r i o d  i s s u f f i c i e n t to  w h i l e no s u c h p h e n o t y p e i s These l i n e s o f e v i d e n c e  a r e s u f f i c i e n t t o s u g g e s t t h a t t h e d e v e l o p m e n t a l d e l a y and a s s o c i a t e d l e t h a l i t y a r e n o t e n t i r e l y a r e s u l t o f rDNA function.  dis-  155-  - Chapter The  The  Bristle  o r i e n t a t i o n and  effect associated  c o n d i t i o n i s the a l t e r a t i o n of  expression.  c h a n g e s , a v a r i e t y o f X/0  m a l e s have been g e n e r a t e d  f o r t y i n d i v i d u a l s w e r e e x a m i n e d and  s c u t e b r i s t l e s and  t h o r a c i c microchaetae  d i v i d u a l s o f t h e X/X, comparison  o f X/0  X/Y  and X/0  and  F o r each  specexper-  t h e number o f  were r e c o r d e d .  In-  g e n o t y p e were s t u d i e d .  A  males w i t h m a t e r n a l l y or p a t e r n a l l y i n h e r -  s c u t e X-chromosomes was The  bristle  I n an e f f o r t t o q u a n t i t a t e t h e s e  b r i s t l e f r e q u e n c i e s have been r e c o r d e d .  iment,  ited  Phenotypes  most c h a r a c t e r i s t i c p h e n o t y p i c  w i t h t h e s c u t e X/0  ific  8 -  also included.  v a r i e g a t i o n of the achaete  l o c u s was  investigated  b y r e c o r d i n g t h e number o f t h o r a c i c m i c r o c h a e t a e . a c i c e p i d e r m i s t h a t was  utilized  for this  The  s t u d y was  thor-  defined  by t h e a r e a e n c l o s e d by t h e p r e s u t u r a l and p o s t e r i o r p o s t a l a r bristles. and  The  data f o r t h i s study are presented  g r a p h i c a l l y d e p i c t e d i n F i g u r e 15-  c o n f i d e n c e i n t e r v a l s l i e b e t w e e n 4 and  The  i n Table  majority of  10 b r i s t l e s .  13  95$  This  s u g g e s t s t h a t t h e s t a n d a r d d e v i a t i o n s r a n g e f r o m 12 t o 30 i n these data.  T h i s a l s o i n d i c a t e s t h a t 95$  data points w i l l  of the  l i e w i t h i n 24 t o 60 b r i s t l e s  individual  (two  d e v i a t i o n s ) o f t h e mean v a l u e e s t i m a t e d f o r t h e  standard  specific  population. The  d a t a c o l l e c t e d on m i c r o c h a e t a e  b e a r o u t a number o f  TABLE 13 Microchaetae Frequency  x/x  Paternal  X/Y  Maternal X/0  x/o  182.0 +  5.5  179.9 +  9.3  191.3 +  4-2  + 11.6  131.6 +  5-6  220 •1  208.2 + 3 . 7  198 . 4 + 4 . 3  192.4  + 5.5  203 .2 + 4.2  92.7  V2  124.5 + 6.6  138 •3 + 8.0  68.4 +  6.4  S 1 L 8R  219.4 + 4.5  201 •9 + 5-2  116.5 +  9-7  V2L 8R  136.7  + 7-0  127 .8 + 6 . 5  79.8 +  5.6  8L  210.2 + 4 . 3  232 .0 + 3 . 3  192.0 +  4.0  2 0 6 . 9 + 5-1  2 5 3 . 9 + 3.1  258 •1 + 3 . 3  240.4 +  2.4  244.9  sc sc  S 1  L8  +S m  + dl49  8  sc  +  yB  V2R  ± 4.8  160.5 + 10.5  227.8 + 4.2  sc  (95$ c o n f i d e n c e  intervals)  75-1  +  4.7  lZj.1.9 +  4.8  76.5  +  5.5  +3-8  157-  FIGURE 15  B r i s t l e frequency i n a s e r i e s o f s c u t e i n v e r s i o n X/0  I  :  The  microchaetae  males.  158.  i wild  of type  sc  L8  S1  m  SC  n  Bars represent: X/X,  X/Y,  sc  y B (left  to  8  sc  V2  right)  p a t e r n a l l y d e r i v e d X/0,  maternally  derived  X/0  159.  consistent tendencies. in  these experiments  A l l of the scute i n v e r s i o n s reported  e x h i b i t e d a reduced  expression of  thor-  acic microchaetae.  E x c e p t i n g f o r scute-L8, the frequency  microchaetae  males i s g r e a t l y reduced  X/X to  i n X/0  f e m a l e s o r X/Y right,  one  may  males. suggest  As  one  as compared t o  v i e w s F i g u r e 15  from  t h a t the data are arranged  i n c r e a s i n g l y mutant p r o g r e s s i o n w i t h r e s p e c t to the locus.  tant  left  i n an achaete  I t i s v e r y e v i d e n t t h a t s c u t e - L 8 most c l o s e l y  b l e s w i l d type w h i l e scute-V2  of  resem-  e x h i b i t s t h e most s e v e r e  mu-  condition. It  i s -also apparent  that the m a t e r n a l l y derived  X/0  males are l e s s mutant t h a n the males w i t h p a t e r n a l l y  inherited  s c u t e X-chromosomes.  This observation i s consistent  through-  out both microchaetae  and m a c r o c h a e t a e e x p e r i m e n t s  b e l i e v e d to r e s u l t from experiments,  sampling problems.  I n the p a t e r n a l  t h e r e i s a n i s o l a t e d g r o u p o f X/0  ered t h a t are a s s o c i a t e d w i t h g r e a t l y extended and  a more s e v e r e m u t a n t p h e n o t y p e .  not observed  s a m p l i n g f r o m t h e s e two  males recovdevelopment  This specific  i n the maternal experiments  and,  populations result  and i s  group i s  therefore,  i n different  data.  T h i s t h e o r y i s s u b s t a n t i a t e d by d a t a r e c o r d e d i n T a b l e 13 • The  c o n f i d e n c e i n t e r v a l s and  a b l y l a r g e r as a r e s u l t  standard d e v i a t i o n s are  o f t h e s m a l l number o f l i e s  noticethat  d e v i a t e g r e a t l y f r o m t h e mean i n t h e p a t e r n a l e x p e r i m e n t s . It  may  be p o s s i b l e t o e l i m i n a t e t h i s  s o u r c e o f v a r i a n c e by  sampling the f l i e s p r i o r to e c l o s i o n of the g r e a t l y  delayed  160.  individuals. The  v a r i e g a t i o n of the  scute  l o c u s was  i n v e s t i g a t e d by  r e c o r d i n g t h e number o f s c u t e l l a r b r i s t l e s l a t i o n as above.  These d a t a are r e p o r t e d  d e p i c t e d g r a p h i c a l l y i n F i g u r e 16.  The  The  a full  consistent trends.  In a l l cases,  c i a t e d with a dramatic  data  The scute X/0  i n t h e X/0  data are  to the  shows a c o n s i d e r a b l e  most pro-  scute-L8 scute  locus.  of  the  reduction i n  condition.  i n s u f f i c i e n t to e s t a b l i s h d i f f e r e n c e s i n  i n d i v i d u a l s i n h e r i t i n g t h e i r X-chromosome  From a group o f f o r t y i n d i v i d u a l s , t h e r e a r e e v e n t s t o m o n i t o r i n a s i n g l e sample. ances e s t a b l i s h e d i n previous  males  and  maternally. o n l y 160  Judging  bristle  from the  vari-  s t u d i e s f o r macrochaetae  I963) i t w o u l d be i m p r o p e r t o s u g g e s t t h a t a d i f f e r -  e n c e e x i s t s b e t w e e n X/0 tion.  The  expression  e x p r e s s i o n b e t w e e n p a t e r n a l l y d e r i v e d X/0  (Rendel,  asso-  i s the mutant  I t i s apparent that  S c u t e - V 2 most c l o s e l y r e s e m b l e s w i l d t y p e  expression  scutellum.  scutellar  males.  i s t h e most s e v e r e l y a f f e c t e d w i t h r e s p e c t  s c u t e l l a r b r i s t l e s but  value  condition i s  f e m a l e s o r X/Y  to r i g h t .  results  i n d i c a t e a number o f  t h e X/0  c o n s p i c u o u s t r e n d r e v e a l e d by t h e s e  and  This  d e c r e a s e i n t h e number o f  b r i s t l e s as. c o m p a r e d t o X/X  g r e s s i o n from l e f t  o f 160.  complement o f f o u r b r i s t l e s p e r  g r a p h i c a l r e s u l t s of the data  same p o p u -  i n T a b l e lk  w i l d type  v e r y c l o s e l y a p p r o a c h t h e maximum v a l u e represents  i n the  males of d i f f e r e n t p a r e n t a l d e r i v a -  I n v e s t i g a t i o n o f t h i s phenomenon w o u l d r e q u i r e n u m e r o u s  161.  TABLE  14  Scutellar Bristle  X/X  X/Y  113  95  Frequency  Paternal X/0  Maternal X/0  Q1  sc  1  +S  sc  L 8  m  yB  52  56  63  48  14  22  144  129  78  86  147  145  118  114  Q  sc  +dl49  sc^ S1L  8R  132  139  89  99  V2L  8R  151  146  123  129  8L V2R  148  144  131  128  +  155  158  155  157  (raw count o f s c u t e l l a r b r i s t l e s 40 i n d i v i d u a l s )  t  from  162.  FIGURE  16  B r i s t l e frequency i n a s e r i e s o f s c u t e i n v e r s i o n X/0  II  :  The  scutellars  males.  163.  fo  wild  Of  type  100 90  -  I  80  70  •  60  •  50  -  40  -  ~~  1  1  I  1  30  20  10  sc  L8  m  sc  SI  y B  Bars represent: X/X,  X/Y,  sc (left  to  p a t e r n a l l y d e r i v e d X/0,  8  sc  V2  right) maternally  derived  X/0  164.  samples to e s t a b l i s h a t r e n d of t h i s n a t u r e .  The  data  are  s u f f i c i e n t l y r o b u s t t o i n d i c a t e d i f f e r e n c e s between s t o c k s , however. A c o m p a r i s o n o f F i g u r e 15  and 16  tant trends e s t a b l i s h e d f o r these inversely related. severe  i n d i c a t e t h a t the  f o u r scute i n v e r s i o n s are  F o r example, scute-L8  expresses  t h e most  scute phenotype w h i l e m a n i f e s t i n g a v i r t u a l l y  type achaete converse  phenotype.  The  affected.  wild  scute-V2 data represents  s i t u a t i o n as the achaete  mu-  l o c u s i s most  T h i s p o l a r i t y o f e x p r e s s i o n may  the  profoundly  represent a  fund-  amental property of p o s i t i o n e f f e c t v a r i e g a t i o n o p e r a t i n g slightly different scute region. distinctive  euchromatic  b r e a k p o i n t s i n the  A l t e r n a t i v e l y , t h i s r e l a t i o n s h i p may  c a p a c i t i e s of s p e c i f i c regions of  to induce p o s i t i o n e f f e c t v a r i e g a t i o n . of these research.  two  The  on  achaetereflect  heterochromatin  discrimination  p o s s i b i l i t i e s remains a subject f o r f u r t h e r  165-  DISCUSSION  The  preceding  sections of t h i s t h e s i s describe  v e s t i g a t i o n o f many f a c t o r s a s s o c i a t e d s i o n phenotypes. ments are  I t has  associated  w i t h the  and  with a reduction  can  be  are  consolidated  the  phenomena.  The  generation  a l s o a r e s u l t of the  paternal  The  delay  rearrangement. the  These  results  to develop a reasonable explanation  e f f e c t e x p e r i m e n t s ( C h a p t e r 1)  of  corroborate  r e s u l t s p r e s e n t e d by p a s t a u t h o r s ( H e s s , 1962;  1971).  rearrange-  o f macro- and/or micro--  a n o m a l i e s h a v e b e e n s y s t e m a t i c a l l y s t u d i e d and  the  inver-  i n d i v i d u a l s i n d i c a t e s that a developmental  inviability  The  scute  been e s t a b l i s h e d t h a t these  c h a e t a e as a p r i m a r y v a r i e g a t i n g p h e n o t y p e . o f s c u t e X/0  the i n -  phenotypic s t u d i e s of the p a t e r n a l l y  Baker, derived  s c u t e X/0  males i n d i c a t e t h a t each i n v e r s i o n i s accompanied  by  characteristic bristle  a very  both the  g e n e s a c h a e t e and  rangement.  scute  expression. are  D e v e l o p m e n t a l l y , t h e X/0  d i s t u r b e d by males are  o f t e n e x h i b i t s p a s t i c c o n t r o l o f w i n g s and unusual to observe these f l i e s  e x p e r i m e n t s was  X/0  m a l e v i a b i l i t y was  all  cases, the  The  extreme.  the  rear-  retarded  legs.  entrapped i n the  r e s u l t of t h e i r decrepit c o n d i t i o n . i n the p a t e r n a l  I n most c a s e s ,  It is food  lethality  as  and not a  observed  I n most c a s e s ,  15% o r l e s s t h a t o f t h e  control.  a d d i t i o n o f a Y-chromosome i n t o t h e  genome  the In  166.  r e s u l t e d i n r e s t o r a t i o n t o almost normal v i a b i l i t y . The  maternal  e f f e c t experiments (Chapter  1) e x t e n d t h e  w o r k i n i t i a t e d b y H i d e h H a r g e r (197*0 a n d c o r r o b o r a t e h e r d a t a f o r t h e S 1 L 8R chromosome.  The m o s t i m p o r t a n t  concept  d e f i n e d by t h i s experiment i s t h e c o n d i t i o n a l l e t h a l i t y a s s o c i a t e d w i t h t h e s c u t e X/0 m a l e s .  When t h e s c u t e  chromosome  i s i n h e r i t e d p a t e r n a l l y , t h e X/0 i n d i v i d u a l s a r e l a r g e l y i n viable.  H o w e v e r , when t h e X/0 m a l e d e r i v e s i t s s c u t e  X-chro-  mosome f r o m t h e f e m a l e , v i a b i l i t y i s g r e a t l y e n h a n c e d . phenomenon i s t e r m e d t h e s c u t e m a t e r n a l Also associated with the maternal reductions  effect. effect are noticeable  o f s e v e r i t y o f t h e jsc a n d a c v a r i e g a t i n g p h e n o t y p e s  as compared t o t h e p a t e r n a l e f f e c t p h e n o t y p e s .  The  develop-  m e n t a l d e l a y a s s o c i a t e d w i t h t h e s c u t e X/0 m a l e s i s a l s o nificantly The provided  reduced i n t h e maternal  generation  s i m i l a r r e s u l t s t o those  two s t u d i e s ( C h a p t e r  experiments e x h i b i t considerable  v i n g X/0 m a l e s a r e d e v e l o p m e n t a l l y  an  inversions  f u r t h e r m a t e r i a l f o r i n v e s t i g a t i o n . I t i s apparent  observed i n the previous  tant.  sig-  experiments.  o f t h e v a r i o u s recombinant scute  t h a t t h e recombinants produce very  nal  This  The m a t e r n a l  lethality  The p a t e r -  and t h e s u r v i -  r e t a r d e d a n d s e v e r e l y mu-  transmission of the inversion results i n  i n c r e a s e i n X/0 v i a b i l i t y a n d a p a r t i a l  scute-achaete  2).  phenotype.  reversion of the  These e x p e r i m e n t s suggest t h a t t h e  anomalies associated with the scute  inversions are general  phenomena r a t h e r t h a n s p e c i f i c p e c u l i a r i t i e s i n h e r e n t t o t h e  167.  parental  chromosomes.  A number o f a u t h o r s s t u d y i n g m a t e r n a l e f f e c t s h a v e s u g gested t h a t i n d i v i d u a l s d e r i v e d from a female for  heterozygous  a v a r i e g a t i n g gene a r e more m u t a n t t h a n t h o s e ( N o u j d i n , 1944;  f r o m a homozygous f e m a l e S p o f f o r d , 1959). fects  ( C h a p t e r 3)  The  derived 1954;  Luning,  study of the heterozygous maternal ef-  i n d i c a t e t h a t t h e s c u t e X/0  have comparable v i a b i l i t y homozygous s c u t e f e m a l e s .  t o t h o s e X/0  individuals  f l i e s derived  The p h e n o t y p e s t h a t w e r e  from derived  f r o m t h e s e e x p e r i m e n t s were n o t a p p r e c i a b l y d i f f e r e n t t h o s e r e c o v e r e d f r o m homozygous f e m a l e s .  The  than  data also  g e s t t h a t t h e p h e n o t y p e s and i n c r e a s e d r e c o v e r y o f t h e m a l e s was  female.  i n v e s t i g a t i o n of f a c t o r s i n f l u e n c i n g the p a t e r n a l  e f f e c t i n v o l v e d g e n e r a t i n g X/0 genotypes  X/0  i n d e p e n d e n t o f t h e rDNA o r X - h e t e r o c h r o m a t i c c o n -  tent of the parental The  sug-  (Chapter 4).  males w i t h s l i g h t l y  altered  A number o f d u p l i c a t i o n s d i f f e r i n g i n  rDNA c o n t e n t w e r e t r a n s m i t t e d f r o m t h e f e m a l e t o t h e X/0 i n dividual.  A s m a l l , but c o n s i s t e n t i n c r e a s e i n v i a b i l i t y  p e a r s t o be r e l a t e d t o t h e X-chromosome rDNA r e g i o n . t h e s e s m a l l d u p l i c a t i o n s a l s o c a r r i e d an a c t i v e a n d t h e p r e s e n c e o f t h i s f a c t o r i n t h e X/0 increased their v i a b i l i t y .  Two  genome g r e a t l y  Four of the recombinant  a s i g n i f i c a n t decrease i n v i a b i l i t y  l o c u s was  of  scute locus  chromo-  somes r e c o v e r e d w e r e d u p l i c a t e d f o r t h e s c u t e l o c u s . was  ap-  There  when t h e t h i r d  t r a n s f e r r r e d i n t o t h e genome and t h i s m a l e  scute  triplo-  168.  scute and  l e t h a l i t y h a s b e e n p r e v i o u s l y d i s c u s s e d by G a r c i a - B e l l i d o  S a n t a m a r i a (1978).  As t h e d u p l i c a t i o n s a r e l a r g e l y  e r o c h r o m a t i c , one c o u l d a l s o d e t e r m i n e t h a t a component the v i a b i l i t y these  c h a n g e was a s s o c i a t e d w i t h t h i s f a c t o r .  experiments,  foundly  t h e p r e s e n c e o f an a c t i v e s c u t e matin content.  of From  i t i s a p p a r e n t t h a t t h e f a c t o r s most  i n f l u e n c i n g the v i a b i l i t y  het-  pro-  o f t h e s c u t e X/0 m a l e s a r e  l o c u s and g e n o m i c  heterochro-  The p r e s e n c e o f a n X - c h r o m o s o m a l b o b b e d r e -  g i o n a p p e a r s t o be much l e s s  influential.  T h e s e e x p e r i m e n t s were a l s o c o m p l e t e d , w i t h which d i f f e r e d with respect  Y-chromosomes  t o t h e i r rDNA c o n t e n t .  A delation  o f a p o r t i o n o f t h e s h o r t arm o f t h e Y-chromosome r e s u l t e d i n a Ybb" c o n s t i t u t i o n . chromatin  lost  Unfortunately,  t h e amount o f h e t e r o -  i n t h i s rearrangement i s d i f f i c u l t  to quanti-  t a t e o w i n g t o t h e l a c k o f g e n e t i c m a r k e r s on t h e Y-chromos;ome. These s t u d i e s i n d i c a t e t h a t t h e p r e s e n c e o f t h e Ybb" i n t h e s c u t e X/0 genome i s a s s o c i a t e d w i t h a r e d u c e d l e v e l i t y when c o m p a r e d t o t h e Y b b  +  controls.  This  of v i a b i l -  effect could  be  a t t r i b u t a b l e t o t h e l a c k o r rDNA o r a d e f i c i e n c y f o r a n o t h e r f a c t o r r e m o v e d by t h e d e f i c i e n c y . m o d i f i e d Y-chromosomes  Other s t u d i e s involving;  i n d i c a t e that r e s u l t s obtained  from  s u c h e x p e r i m e n t s a r e h i g h l y v a r i a b l e and t h a t t h e v a r i e g a t i o n suppression  activity  o f t h e Y-chromosomal m a t e r i a l s i s n o t a  f u n c t i o n o f the l e n g t h o f the fragment (Baker 1959; H e s s , 1970; B a k e r , 1 9 7 1 ) very  and  Spofford,  I t seems v e r y p o s s i b l e  l o c a l i z e d a r e a s o f t h e Y-chromosome may  exert  that  profound  169-  e f f e c t s on v a r i e g a t i o n . Maternal  (  effect  same chromosomes. bility  were c a r r i e d , o u t f o r t h e s e  The m a j o r f a c t o r i n f l u e n c i n g X/0 m a l e v i a -  a p p e a r s t o be t h e p r e s e n c e  bobbed r e g i o n . ser  experiments  extent.  lethality  of the standard  Y-chromosome  The o t h e r f a c t o r s m o d i f i e d v i a b i l i t y  These experiments  to a  w e r e most s e n s i t i v e t o t h e  a s s o c i a t e d w i t h t h r e e doses o f t h e s c u t e gene. A l l  o f t h e r e c o m b i n a n t chromosomes c a r r y i n g two s c u t e l o c i a dramatic plied  les-  decrease  i n viability  t o the system.  scute l e t h a l i t y  showed  when a t h i r d l o c u s was  sup-  These d a t a i n d i c a t e t h a t t h e t r i p l o -  i s a phenomenon  independent of the maternal  effect. In  the course  o f these  t h e compound X-chromosome type  s t u d i e s , i t became a p p a r e n t  that  c o n s t i t u t i o n i n f l u e n c e d t h e pheno-  o f s c u t e X/0 m a l e s ( C h a p t e r  discovered that the v i a b i l i t i e s  5).  Fortuitously,  of these  i t wa:::  individuals  was  v a r i a b l e a n d d e p e n d e n t u p o n t h e p a r t i c u l a r compound-X  female  f r o m w h i c h t h e y were r e c o v e r e d .  this  I t i s suspected  that  d i f f e r e n c e i n v i a b i l i t y may be due t o t h e d i f f e r i n g chromatic  hetero-  c o n t e n t s r e s u l t i n g f r o m t h e c o n s t r u c t i o n o f com-  p o u n d X-chromosomes.  The m o s t v i a b l e  d e r i v e d f r o m a compound-X somal h e t e r o c h r o m a t i n . the heterochromatic  s c u t e X/0 f l i e s a r e  which contains accessory  Unfortunately, l i t t l e  content  Y-chromo-  i s known  of the other attached  about  X-chromo-  somes and t h u s , a n y p r o p o s a l o f a m e c h a n i s m f o r t h i s p h e n o menon w o u l d be e n t i r e l y s p e c u l a t i v e .  170.  Temperature i s a c l a s s i c m o d i f i e r o f p o s i t i o n - e f f e c t variegation  (Chapter 6 ) .  F o r t h e s c u t e m u t a t i o n , one o b s e r -  v e s a more s e v e r e p h e n o t y p e a t l o w e r t e m p e r a t u r e s a n d i n c r e a s i n g l y w i l d phenotypes  a s one a p p r o a c h e s  29°C.  Mutants  with  d i s t u r b a n c e s i n rRNA f u n c t i o n p r e s e n t a n o p p o s i t e d e v e l o p m e n tal profile.  A t l o w t e m p e r a t u r e s , t h e bobbed mutants a r e a b l e  t o compensate f o r t h e m u t a t i o n and t h i s r e s u l t s i n a l e s s t a n t p h e n o t y p e (Mohan a n d R i t o s s a , 1 9 7 0 ) .  At higher  t u r e s , d e v e l o p m e n t i s more r a p i d , c o m p e n s a t i o n a more s e v e r e p h e n o t y p e r e s u l t s .  mu-  tempera-  i s l i m i t e d , ! and  The d e f i n i t i o n o f a  tempera-  t u r e e f f e c t i n v o l v e d w i t h t h e s c u t e X/0 l e t h a l i t y may p r o v i d e e v i d e n c e s u p p o r t i n g one o f t h e s e two d e v e l o p m e n t a l  pathways.  These experiments i n d i c a t e t h a t t h e l e t h a l i t y a s s o c i a t e d w i t h s c u t e X/0 m a l e s i s more s e v e r e a t r e d u c e d There 29°  temperatures.  i s no s i g n i f i c a n t d i f f e r e n c e b e t w e e n v i a b i l i t e s a t  o r 25° b u t t h e r e i s a c o n s i d e r a b l e r e d u c t i o n i n v i a b i l i t y  o b s e r v e d a t 18°.  T h i s e f f e c t was r e c o g n i z e d i n b o t h  maternal  and p a t e r n a l e x p e r i m e n t s a n d t h i s p r o v i d e s e v i d e n c e t h a t t h e l e t h a l i t y a s s o c i a t e d w i t h t h e s c u t e i n v e r s i o n s may be c o n comitant w i t h d i s t u r b a n c e s o f the euchromatic r a t h e r t h a n d i s r u p t i o n o f t h e rRNA  scute functions,  system.  B o t h rDNA d e f i c i e n c i e s a n d s c u t e i n v e r s i o n m u t a n t s a r e a s s o c i a t e d w i t h r e t a r d e d development.  I n an e f f o r t t o d i s -  c r i m i n a t e b e t w e e n t h e s e two phenomena, t h e d e v e l o p m e n t o f b o t h b o b b e d a n d s c u t e X/0 i n d i v i d u a l s h a s b e e n s t u d i e d w i t h r e s p e c t t o t h e d e l a y i n m a t u r a t i o n and t h e r e s u l t a n t pheno-  171 •  type  (Chapter 7)•  I n the p a t e r n a l experiments,  m u t a n t s a r e d e v e l o p m e n t a l l y d e l a y e d b y two characteristic  s c u t e phenotypes f o r each  the  d a y s and  The  developmental  ever observed  mutants.  The  No  effect  bobbed mutants a l s o produced The  t h a t a one  t o two  and  involving  any v i s i b l e . b o b b e d p h e n o t y p e .  individuals,  d e l a y and b o b b e d p h e n o -  This evidence  developmental a result The  d e l a y and  o f rDNA final  mutants.  day d e l a y i s s u f f i c i e n t The  delay  i s c o n s i s t e n t l y two day:;;  These r e s u l t s suggest delays are  that  different  i s s u f f i c i e n t to suggest  t h a t the  a s s o c i a t e d l e t h a l i t y are not  entirely  disfunction.  chapter i n v e s t i g a t e d the b r i s t l e  phenotypes  t h a t were a s s o c i a t e d w i t h t h e v a r i e g a t i n g a c h a e t e - s c u t e (Chapter 6).  The  to  males are not a s s o c i a t e d w i t h  t h e s c u t e and b o b b e d d e v e l o p m e n t a l phenomena.  the  d i f f e r e n t bobbed  i n the scute experiments  l o n g e r and y e t , t h e s e X/0  the  n o t e d f o r t h e bobbed  produce a c o n s i d e r a b l y severe bobbed phenotype. observed  No  experiments  as compared t o  s t r o n g l y bobbed  c o r r e l a t i o n of developmental  i s apparent  i n the  experiments  t y p e h a s b e e n e s t a b l i s h e d f o r two It  in  d e l a y a s s o c i a t e d w i t h the scute mater-  s u c h d i f f e r e n c e was  maternal  day  inversions.  n a l e f f e c t s i s s i g n i f i c a n t l y reduced paternal delay.  The  and w e r e b o b b e d i n p h e n o t y p e .  s u c h b o b b e d p h e n o t y p e was i n v o l v e d w i t h the scute  exhibit  inversion.  b o b b e d m u t a n t s w e r e d e v e l o p m e n t a l l y d e l a y e d by one the p a t e r n a l experiments  scute  d a t a c o l l e c t e d on t h e m i c r o c h a e t a e  locus  indicate  172.  that there are c h a r a c t e r i s t i c  l e v e l s of b r i s t l e  f o r e a c h i n v e r s i o n and. t h i s l e v e l o f a Y-chromosome.  i s reduced  expression  i n the absence  T h e r e a p p e a r s t o be a m u t a n t p r o g r e s s i o n  that i s a s s o c i a t e d w i t h the s p e c i f i c breakpoints of the i n versions  ( s e e F i g u r e s 15 and 1 6 ) .  The i n v e r s i o n s c u t e - L 8 ,  r e p r e s e n t s t h e most, w i l d t y p e m u t a n t w h i l e s c u t e - V 2  represents  t h e most s e v e r e m u t a n t s t o c k w i t h r e s p e c t t o t h e a c h a e t e The d a t a c o n c e r n e d  w i t h t h e s c u t e gene s u g g e s t s  mutant p r o g r e s s i o n a l s o e x i s t s f o r t h i s l o c u s .  achaete  l o c u s as scute-L8  scute-V2 i s predominantly r e s u l t from the s p e c i f i c to the scute l o c u s . specific  abilities  that a  Most  c a n t l y , the p r e g r e s s i o n i s opposite t h a t observed  signifi-  f o r the  i s t h e most s e v e r e l y a f f e c t e d , w h i l e w i l d type.  T h i s d i f f e r e n c e may  euchromatic  I t a l s o may  breakpoints with respect  be a d e q u a t e l y  of heterochromatin  T h e s e m u t a n t p r o g r e s s i o n s may  e x p l a i n e d by  to induce v a r i e g a t i o n .  represent differences r e s u l t i n g  from the v a r i e t y o f heterochromatic  breaks.  More  comprehen-  s i v e s t u d i e s must be c o m p l e t e t o e s t a b l i s h t h e b a s i s f o r these  phenomena. The m a j o r o b j e c t i v e o f t h i s r e s e a r c h h a s b e e n t o  examine t h e p a r e n t - s o u r c e  e f f e c t and t o d e t e r m i n e  cause o f t h e scute i n v e r s i o n l e t h a l i t y A number o f a u t h o r s h a v e s u g g e s t e d  and  cistrons  S n y d e r , 1973a,  (Baker,  b, 1 9 7 5 ) -  (Hess,  the  1962).-  t h a t t h i s phenomenon  i s associated with a position effect r i b o s o m a l RNA  locus.  suppression of the  1971; N i x , 1973; However,  Puckett  d a t a r e p o r t e d by  173-  H a r g e r (197*0 i n d i c a t e d ' t h a t t h e l e t h a l i t y m a l e s was  c o n d i t i o n a l and  of scute  dependent upon the  source of the  scute  X-chromosome.  have p r o v i d e d  f u r t h e r evidence suggesting  X/0  parental  These i n v e s t i g a t i o n s  mary d e f e c t r e s p o n s i b l e f o r l e t h a l i t y  t h a t the  i s not  the  pri-  variega-  t i o n o f t h e rDNA c i s t r o n s . The  data from these s t u d i e s are  those of previous  i n agreement  a u t h o r s ( H e s s , 1962;  with  1971»  Baker,  H a r g e r , 197*0 . i n d e m o n s t r a t i n g a c o n s i s t e n t l e v e l inviability V2 . and  sc  o f X/0 .  males c a r r y i n g the •  SI  , sc  L8  8 , sc ,. . . .  i n v e r s i o n s when t h i s r e a r r a n g e m e n t i s i n h e r i t e d  paternally.-  Moreover, the p r e v i o u s l y reported ( H a r g e r 197*+) h a s  rescue of t h i s l e t h a l i t y  s t r a t e d f o r a l l f o u r of the It  sc  of  i s apparent t h a t the  i s a general  scute  a n o m a l y c a n be Should the  inviability  rDNA f u n c t i o n , one  o f s c u t e X/0  scute  greatly modified  b e e n demon-  i n v e r s i o n chromosomes.  inviability  phenomenon o f t h e  t h a t has  results. scute  nurse c e l l s .  Conversely,  egg  w o u l d be  rDNA d e f e c t i v e n u r s e c e l l s  one  would expect the  s u l t i n g z y g o t e t o be This hypothesis  X-  been amply sup-  w i t h maternal i n h e r i t a n c e , the and  source.  impaired  sperm c a r r y i n g t h e  p l i e d w i t h rRNA f r o m s u r r o u n d i n g  the  by v a r y i n g p a r e n t a l  r e s u l t f r o m an  chromosome f e r t i l i z e s an egg  males  i n v e r s i o n s and  would p r e d i c t c o n t r a s t i n g  P a t e r n a l l y i n h e r i t e d , the  maternal  furnished  l e s s adequately furnished with  p r e d i c t s t h a t v i a b i l i t y w o u l d be  by  rerRNA.  enhanced  174. if  sperm c a r r y i n g t h e s c u t e X-chromosome f e r t i l i z e d  egg f u l l y f u r n i s h e d w i t h rRNA. site  t o the observed  This i s entirely  an  oppo-  results.  Experiments i n v o l v i n g females heterozygous f o r bb~  chromosomes a n d t h e s c u t e i n v e r s i o n s a l s o  indicate  t h a t t h e rDNA c o m p l e m e n t i s n o t a c r u c i a l f a c t o r . nurse c e l l s  i n the v i c i n i t y  The  o f t h e m a t u r i n g egg a r e d e -  p e n d e n t s o l e l y on t h e s c u t e X-chromosome f o r t h e i r temp l a t e rDNA.  S c u t e X/0 m a l e s d e r i v e d f r o m  individuals  h e t e r o z y g o u s f o r a bb~ a r e c o m p a r a b l y v i a b l e t o f e m a l e s h e t e r o z y g o u s f o r a s t a n d a r d X-chromosome. In  t h e c o u r s e o f t h e s e e x p e r i m e n t s , i t was demon-  strated that both  Si t h e sc  18 and sc  inversions are  n o r m a l l y v i a b l e a n d f e r t i l e when h e t e r o z y g o u s f o r t h e sc  4L - 8R sc bb  Nix  chromosome.  T h i s was f i r s t  r e p o r t e d by  (1971) a n d i s c o n t r a r y t o t h e rDNA d e f e c t h y p o t h e s i s . SI  T h e s e two i n v e r s i o n s  (sc  L8 and sc  ) show t h e most s e v e r e  lethality  p r o f i l e s and a r e s e m i - s t e r i l e a s homozygous  females.  Should these problems a r i s e from  difficulties  i n p r o d u c i n g rRNA, one w o u l d e x p e c t f e m a l e s h e t e r o z y g o u s for  rDNA d e f i c i e n c i e s t o be e v e n more s e v e r e l y SI  T h i s i s n o t t h e case as t h e sc h e t e r o z y g o u s w i t h a n NO~-X  affected.  IJ8  and s c  inversions,  chromosome, a r e n o r m a l l y  v i a b l e and f e r t i l e . It  s h o u l d be n o t e d t h a t t h i s a n o m a l y c o u l d be e x -  p l a i n e d i n t e r m s o f t h e rDNA r e g u l a t o r y m e c h a n i s m s .  1  175.  The phenomenon o f rDNA c o m p e n s a t i o n in  r e s u l t s i n an i n c r e a s e  rDNA c o n t e n t s o l e l y i n s o m a t i c c e l l s when t h e X chromo-  some i s o p p o s i t e a rDNA d e f i c i e n t chromosome ( S h e r m o e n and ii8  SI  K i e f e r , 1975).  I t i s p o s s i b l e t h a t t h e sc  and sc  homozygotes a r e u n a b l e t o compensate f o r t h e i r d e f e c t in  rRNA p r o d u c t i o n a s t h e y h a v e a w i l d t y p e c o m p l e m e n t  of  rDNA ( N i x , 1973) -  bb~ of  The f e m a l e s - h e t e r o z y g o u s f o r t h e  chromosome h a s a s i g n i f i c a n t l y l o w e r t e m p l a t e number rDNA c i s t r o n s a n d t h i s may t r i g g e r t h e  mechanism.  compensatory  I t has been p r e v i o u s l y observed t h a t the  r e c o g n i t i o n f a c t o r i n rDNA c o m p e n s a t i o n i e n c y o f rDNA c i s t r o n s  i s the defic-  ( T a r t o f , 1973) a n d t h i s c o u l d a c -  count f o r t h e v i g o r o f t h e sc  / bb  and sc  / bb J_J8  SI  A n o t h e r anomaly s p e c i f i c  females.  t o t h e sc  and sc  chromo-  somes i s a n a b n o r m a l l y f r e q u e n t o c c u r e n c e o f s e c o n d meiotic division  (M-2) n o n d i s j u n c t i o n i n m a l e s .  This  r e s u l t e d i n h o m o z y g o u s f e m a l e s w i t h a n d w i t h o u t Y chromosomes i n many e x p e r i m e n t s a n d p r o v i d e d t h e f i r s t t u n i t y t o t e s t these females f o r f e r t i l i t y ernal effect.  oppor-  a n d t h e mat-  I t was d e t e r m i n e d t h a t t h e homozygous  f e m a l e s w i t h a Y chromosome were n o r m a l l y f e r t i l e w h i l e the It  f e m a l e s l a c k i n g a Y chromosome were was d i s c o v e r e d t h a t t h e f e r t i l i t y  semi-sterile.  of these  c o u l d be g r e a t l y e n h a n c e d i f t h e f l i e s  females  were i s o l a t e d f o r  a n i n t e r v a l b e f o r e b e i n g mated.. I t i s a p p a r e n t motor f u n c t i o n s g r e a t l y improve  that  d u r i n g t h e i n t e r v a l and  176.  t h i s may r e p r e s e n t a m a t u r a t i o n p r o c e s s t h a t i s n e c e s s a r y for  fertility. The s e c o n d  d i v i s i o n n o n d i s j u n c t i o n was  observed  SI w i t h the sc chromosomes n o t c a r r y i n g t h e d l - 4 - 9 L8 and t o a l e s s e r e x t e n t , w i t h t h e s c frequency approached  2% i n t h e s c  inversion  chromosome.  The  y B +S/ Y s t o c k a n d  was l e s s p r o n o u n c e d i n a l l o t h e r s . One w o u l d n o t expect 18 SI sc n o n d i s j u n c t i o n a l females t o occur as o f t e n as sc females as they are n o t comparably periments  ( i n preparation).  v i a b l e i n o t h e r ex-  T h i s i s a l s o i n d i c a t e d by L8  t h e f a c t t h a t t h e m a j o r i t y o f sc  1  f e m a l e s were r e c o v e r -  ed w i t h Y-chromosomes. An i m p o r t a n t f i n d i n g i l l u s t r a t e d by t h e experiments  concerns  the v i a b i l i t y  recombinant  o f S I L 8R/0  males.  T h i s rearrangement c a r r i e s the n u c l e o l a r o r g a n i z e r o f t h e SI SI sc chromosome b u t d o e s n o t e x h i b i t a s c viability g profile,  but r a t h e r t h a t o f t h e sc  chromosome.  Baker  (1971) a t t r i b u t e d t h i s c o n t r a d i c t i o n t o a " n e g a t i v e r e g ulator" property of the proximal  X-heterochromatin.  A s i m p l e r a n d t e s t a b l e h y p o t h e s i s v/ould i n v o l v e t h e v a r i e g a t e d e x p r e s s i o n o f t h e r e a r r a n g e d scute genes. The s e r i e s o f e x p e r i m e n t s X-chromosome of  involving  d u p l i c a t i o n s suggest  t h e X-chromosome  heterochromatic  t h a t t h e bobbed r e g i o n  i s not the major f a c t o r  the increased v i a b i l i t y  o f scute-X/Dp males.  b e a r i n g males a r e comparably  determining Duplication  v i a b l e whether the d u p l i -  177.  c a t i o n c a r r i e s an a c t i v e X n u c l e o l u s o r g a n i z e r o r  not.  I t appears t h a t the  pre-  extra heterochromatin  s e n c e o f a n e x t r a s c u t e gene c o n t r i b u t e more t o t h e s o m a l rDNA  increased v i a b i l i t y  and  the  significantly  t h a n d o e s a d d e d X-chromo-  cistrons.  Although  the X bobbed r e g i o n i s n o t  a large increase i n v i a b i l i t y ,  i t i s apparent t h a t  Y-chromosomal bobbed r e g i o n i s . d e f i n i n g the  extent  i s due  i n the v i c i n i t y  the  Owing t o p r o b l e m s i n  o f t h e d e l e t i o n i n t h e Ybb~  some, i t i s i m p o s s i b l e in viability  responsible for  chromo-  to determine whether t h i s  increase  t o t h e rDNA c i s t r o n s o r o t h e r f a c t o r s  o f the Y-bobbed r e g i o n  (Brosseau,  1964).  A d e c r e a s e i n t e m p e r a t u r e r e s u l t s i n a more m u t a n t expression  of the v a r i e g a t i n g scute l o c u s  w h i l e c a u s i n g l e s s mutant e x p r e s s i o n strains  (Mohan and  R i t o s s a , 1970) .  demonstrated i n these ality  i s more s e v e r e  evidence does not  (Child,  i n rDNA The  1935)  deficient  temperature  effect  experiments i n d i c a t e t h a t the at reduced temperatures.  support  Baker's hypothesis  leth-  This as t h e i n -  creased  d e v e l o p m e n t a l t i m e a s s o c i a t e d w i t h r e d u c e d temp-  erature  should  a l l o w f o r accommodation o f a d e f e c t  in  rRNA s y n t h e s i s . The  most c o n v i n c i n g p h e n o t y p i c  contrary to Baker's hypothesis o f t h e X/0  males.  i s the b r i s t l e  Other authors  o f rRNA a c c u m u l a t i o n  and  evidence that i s phenotypes  h a v e shown t h a t t h e  rate  b r i s t l e length i s proportional  178.  t o t h e number o f rDNA c i s t r o n s (Weinman, 1 9 7 2 ; Shermoen and K e i f e r , 1 9 7 5 ) -  I i " t h e rDNA c i s t r o n s a r e t r u e l y  v a r i e g a t i n g , one w o u l d  e x p e c t .cbo f i n d a r a n g e o f b o b b e d  i n d i v i d u a l s among t h e s u r v i v i n g s c u t e X/0  males.  These  i n d i v i d u a l s w e r e n e v e r o b s e r v e d i n any e x p e r i m e n t s i n volved  w i t h the scute  delay  chromosomes.  The  developmental  e s t a b l i s h e d f o r t h e b o b b e d i n d i v i d u a l s i s some-  w h a t l e s s t h a n t h a t f o u n d f o r t h e s c u t e X/0 nonetheless, This  males;  i t r e s u l t s i n a p r o f o u n d bobbed  i n d i c a t e s that the developmental delay  istic  of the scute  with a defect  phenotype. character-  i n v e r s i o n s i s not d i r e c t l y  associated  i n v o l v i n g t h e rDNA c i s t r o n s .  These r e s u l t s suggest t h a t t h e p r i m a r y  biochemical  d e f e c t s , which cause the l e t h a l i t y a s s o c i a t e d scute  but,  with  i n v e r s i o n s , do n o t i n v o l v e t h e rRNA g e n e s ,  the  but  r a t h e r the euchromatic, achaete-scute l o c u s . The  recent  genetic  d i s s e c t i o n and  a n a l y s i s of achaete-scute mutants  developmental  indicate that  the  f u n c t i o n o f t h i s complex l o c u s i n v o l v e s the d i f f e r e n t i a t i o n of nerve elements 1978;  ( G a r c i a - B e l l i c o and  Garcia-Bellido, 1979).  ported  suggests that a c t i v i t y  24-48 hours p r i o r t o puparium  The  Santamaria,  evidence thusfar r e -  of the scute formation  gene o c c u r s  and t h i s i s  c o n s i s t e n t w i t h the d i f f e r e n t i a t i o n of p e r i p h e r a l elements. propose  G a r c i a - B e l l i d o and S a n t a m a r i a  that the l e t h a l of scute  (1978)  nerve  also  ( l ' s c ) r e g i o n may  be  179.  involved with a c e n t r a l nervous ations at t h i s locus c o o r d i n a t i n g motor There  s y s t e m f u n c t i o n a s mut-  are a s s o c i a t e d  w i t h problems  functions.  a r e numerous e x p e r i m e n t s i n t h i s t e x t  suggest t h a t v a r i e g a t i o n at the scute the  observed l e t h a l i t y .  e x h i b i t m o b i l i t y problems Apparently, problem  in  the f l i e s  which  locus results i n  S c u t e i n v e r s i o n X/0  males  often  directly after eclosion.  are able  t o compensate f o r t h i s  as normal m o b i l i t y i s a c h i e v e d a f t e r a 1 or 2  day i n t e r v a l .  This  i s consistent with variegation of  1 ' s c , a l o c u s t h o u g h t t o be i n v o l v e d w i t h m o t o r G a r c i a - B e l l i c o and S a n t a m a r i a One  functions  1978).  o f the major f a c t o r s observed to modify  l e t h a l i t y was  t h e p r e s e n c e o f an a c c e s s o r y  scute  the locus.  I n the experiments i n v o l v i n g heterochromatic d u p l i c a t i o n s and t h e s c u t e  gene, a c o n s i s t e n t  increase  in viability  could  be a t t r i b u t e d t o t h e p r e s e n c e o f a f u l l y  scute  locus.  I t was  a l s o o b s e r v e d , i n many e x p e r i m e n t s ,  t h a t the s e v e r i t y of the scute ated with  the length  phenotype  c o u l d be  of developmental delay  gree o f motor d i s a b i l i t y . lished  functional  The  i n the temperature-effect  and t h e  lethality profile experiments also  gested the involvement of the scute  locus..  correlde-  estabsug-  It i s this  evidence that supports the concept that p o s i t i o n e f f e c t v a r i e g a t i o n o f the complex a c h a e t e - s c u t e l o c u s r e s u l t s i n X/0  male l e t h a l i t y r a t h e r t h a n a p o s i t i o n e f f e c t  180.  s u p p r e s s i o n o f the rRNA c i s t r o n s . Of p a r t i c u l a r i n t e r e s t to r e s e a r c h e r s i n many f i e l d s i s the i d e n t i f i c a t i o n o f the heterochromatic b r e a k p o i n t V2 m  .  sc  I t i s apparent t h a t both ends o f t h i s  inver-  s i o n r e t a i n a complement o f rDNA t h a t i s s u f f i c i e n t t o produce a normal phenotype.  I t seems v e r y l i k e l y  that  t h i s i n v e r s i o n o r i g i n a t e d w i t h a heterochromatic break w i t h i n the rDNA c i s t r o n s and a euchromatic break w i t h i n the achaete-scute l o c u s .  The r e s u l t i n g chromosome has  rDNA c i s t r o n s d i r e c t l y a b u t t i n g the euchromatic achaetescute l o c u s (See F i g u r e l ) .  The experiments  involved  V2 w i t h sc  suggest v a r i e g a t i o n f o r ac and Hw and, to a  l e s s e r extent, f o r _sc (See Chapter 8 ) .  As the achaete-  scute r e g i o n i s supposedly bordered by "euchromatic" rDNA c i s t r o n s i n t h i s i n v e r s i o n , the v a r i e g a t i o n i n t h i s chromosome i s somewhat s u r p r i z i n g and suggests t h a t the: b i o c h e m i c a l nature o f the n u c l e o l a r o r g a n i z e r r e g i o n may d i f f e r from more c l a s s i c a l euchromatic  loci.  V2 The  sc  experiments a l s o p r o v i d e f u r t h e r evidence  i n f a v o r o f a scute gene l e t h a l i t y r a t h e r than r i b o s o m a l c i s t r o n disturbance.  I n t h i s i n v e r s i o n , the r i b o s o m a l  genes are d i v i d e d i n t o two b l o c k s and separated at opp o s i t e ends o f the chromosome.  Of the scute i n v e r s i o n s ,  t h i s i s the o n l y example where the i n t e g r i t y o f the nuwould expect sc /0 males t o e x h i b i t severe v i a b i l i t y c l e o l a r o r g a n i z e r i s d i r e c t l y d i s t u r b e d and thus one V2  181.  problems.  Quite  t o t h e c o n t r a r y , sc  more v i a b l e t h a n s i m i l a r F r o m C h a p t e r 8 one type be  i s predominantly  sc  8  , sc  S1  /0  , o r sc  m a l e s a r e much T  8  males.  observes that the b r i s t l e  a c h a e t e v a r i e g a t i n g and  c o r r e l a t e d w i t h the  observed l e t h a l i t y .  the v i a b i l i t y and  o f t h e X/0  males.  i n t e r p r e t a t i o n of these  p e r s u e d and  the data  r e l a t i n g to the  can  greater higher  Further investigation  a n o m a l i e s a r e now  should provide  s t r u c t u r e and  this  The  the achaete c h a r a c t e r of the v a r i e g a t i o n , the  pheno-  valuable  being information  r e g u l a t i o n of the  rDNA  cistrons.  The  p u r p o s e o f t h i s t h e s i s has  a more r e f i n e d k n o w l e d g e o f t h e l e t h a l i t y a s s o c i a t e d w i t h the data  been to e s t a b l i s h  f a c t o r s i n f l u e n c i n g the  scute  inversions.  The  s u g g e s t t h a t t h i s phenomenon i s d e p e n d e n t u p o n  p a r e n t a l source n a l e f f e c t has  o f t h e r e a r r a n g e m e n t and been e s t a b l i s h e d .  thus, the  the mater-  R e s u l t s f r o m numerous  experiments suggest t h a t the primary  biochemical  defect  i n v o l v e d w i t h the l e t h a l i t y r e s u l t s from p o s i t i o n e f f e c t v a r i e g a t i o n a t the achaete-scute  locus rather than  the  n u c l e o l a r o r g a n i z e r r e g i o n , as p r e v i o u s l y suggested (Baker,  1971).  nucleolus  The  d i s c o v e r y of the d i v i s i b i l i t y  o r g a n i z e r and  i t ' s subsequent a b i l i t y  of  the  to i n -  d u c e p o s i t i o n e f f e c t v a r i e g a t i o n i s a t o p i c f o r immediate attention.  Although  i t a p p e a r s t h a t most o f  the  182.  genetic dissection  o f t h i s problem has been  completed,  t h e r e a r e n u m e r o u s b i o c h e m i c a l and d e v e l o p m e n t a l lems which remain u n e x p l o r e d . of f i n e major  structural  prob-  The m o d e r n t e c h n i q u e s  a n a l y s i s promise to p r o v i d e the next  advance i n t h i s  problem.  183.  BIBLIOGRAPHY  A g o l , I . J . (1930) Evidence Anat. Rec. 47_ p. 3 8 5 . A g o l , J.Y.' (1929) melanogaster. #3-4.  o f t h e d i v i s i b i l i t y o f t h e gene  Step a l l e l o m o r p h i s m i n D r o s o p h i l a Allelomorph scute-5 J . Exp. B i o l . 4  A s h t o n , F. and J . S c h u l t z ( 1 9 7 1 ) The t h r e e d i m e n s i o n a l f i n e s t r u c t u r e o f chromosomes i n a prophase D r o s o p h i l a nucleus Chromosoma _3J| p . 3 8 3 . Bahn, E. (1971) P o s i t i o n - e f f e c t v a r i e g a t i o n f o r an i s o amylase i n D r o s o p h i l a melanogaster H e r e d i t a s 6j_ p. 7 9 Baker, W.K. (1968) Position-effect variegation Genet. 14 p. 641.  Adv.  Baker, W.K. (1971) E v i d e n c e f o r p o s i t i o n e f f e c t suppress i o n o f t h e r i b o s o m a l RNA c i s t r o n s i n D r o s o p h i l a melanogaster P r o c . N a t l . Acad. Sci.USA 68 p. 2 4 7 2 . Baker, W.K. and A. R e i n (1962) The dichotomous a c t i o n o f Y-chromosomes on t h e e x p r e s s i o n o f p o s i t i o n - e f f e c t v a r iegation G e n e t i c s 47_ p. 1 3 9 9 Baker, W.K. and J.B. S p o f f o r d (1959) Heterochromatic t r o l of position-effect variegation i n Drosophila U n i v e r s . Tex. P u b l . 5914 p. 1 3 5 .  con-  B a l d w i n , M.C. and D.T. S u z u k i (1971) A screening procedure f o r d e t e c t i o n o f p u t a t i v e d e l e t i o n s i n p r o x i m a l heterochromatin of Drosophila Mut. Res. I I p. 2 0 3 . Ben-Zeev, N.. and R. F a l k (1966) Absence o f Y-suppressed l e t h a l s i n an autosome o f D r o s o p h i l a Mutat. Res. 3_ p. 1 7 4 . B e r l o w i t z , L. (1965) Analysis of histone i n situ i n developmentally i n a c t i v a t e d chromatin Proc. N a t l . Acad. S c i . USA j?4 p. 4 7 6 . B l u m e n f e l d , M. (1979) P h o s p h o r y l a t e d HI h i s t o n e i n D r o s o p h i l a melanogaster Biochem. Genet. 1_7_ p. 1 6 3 . B l u m e n f e l d , M. and H.S. F o r r e s t (1971) I s D r o s o p h i l a d.^T on t h e Y-chromosome? P r o c . N a t l . Acad. S c i . USA 68 p. 3 1 4 5 .  184.  B l u m e n f e l d , M.; J.W. O r f , B . J . S i n a , R.A. K r e b e r , M.A. C a l l a h a n , J . I . M u l l i n s a n d L.A. S n y d e r ( 1 9 7 8 ) Correlations between p h o s p h o r y l a t e d HI h i s t o n e s a n d s a t e l l i t e DNAs i n Drosophila v i r i l i s P r o c . N a t l . A c a d . S c i . USA 23. P - 8 6 6 . B r i d g e s , C.B. ( 1 9 1 3 ) of D r o s o p h i l a  N o n - d i s j u n c t i o n o f t h e sex-chromosomes J . E x p . Z o o l . 1J5 p . 5 8 7 .  B r i d g e s , C. a n d T.H. M o r g a n ( 1 9 2 3 ) The t h i r d - c h r o m o some g r o u p o f m u t a n t c h a r a c t e r s o f D r o s o p h i l a m e l a n o gaster. Publ. Carnegie I n s t i t . 32? p . l . B r o s s e a u , G.E. J r . ( 1 9 6 0 a ) V-type e f f e c t s i n f l u e n c i n g the action of the Bar locus i n Drosophila G e n e t i c s 4jl -. 9 7 9 .  B r o s s e a u , G.E. ( 1 9 6 0 b ) G e n e t i c a n a l y s i s o f t h e male t i l i t y f a c t o r s on t h e Y-chromosome o f D r o s o p h i l a melanogaster G e n e t i c s 4j> p . 2 5 7 -  fer-  B r o s s e a u , G.E. J r . ( 1 9 6 4 ) Evidence t h a t heterochromatin does n o t suppress V-type p o s i t i o n e f f e c t G e n e t i c s J50 P- 2 3 7 B r o w d e r , L.W. a n d J . H . W i l l i a m s o n (1976) The e f f e c t s o f cinnamon on x a n t h i n e d e h y d r o g e n a s e , a l d e h y d e o x i d a s e , and p y r i d o x a l o x i d a s e a c t i v i t y d u r i n g d e v e l o p m e n t i n Drosophila melanogaster Dev. B i o l . £3_(2) p. 2 4 l . C h e n , S. ( 1 9 4 8 ) Temperature e f f e c t i n t h r e e mosaic mutants of D r o s o p h i l a melanogaster B u l l . B i o l . France Belg. 82 p. 1 1 4 . C h i l d , G.P. ( 1 9 3 5 ) P h e n o g e n e t i c s t u d i e s on s c u t e - 1 o f Drosophila melanogaster. I . The a s s o c i a t i o n s b e t w e e n t h e b r i s t l e s a n d t h e e f f e c t s o f g e n e t i c m o d i f i e r s and. temperatures. G e n e t i c s _20 p . 1 0 9 • C l e v e r , U. ( i 9 6 0 ) Der e i n f l u s s der s i n n e s z e l l e n a u f d i e Borstenentwicklung bei G a l l e r i a m e l l o n e l l a • Wilh. Roux. A r c h . 1 5 2 p. 1 3 ? . C l i n e , T.W. (1976) A s e x - s p e c i f i c , temperature s e n s i t i v e maternal e f f e c t of the daughterless mutation of Drosophila melanogaster G e n e t i c s _84 p . 7 2 3 C o o p e r , K.W. ( 1 9 5 8 ) A probable heterochromatic deficiency i n I n ( l ) s c u t e - L 8 , t h e approximate l o c a t i o n o f b b and t h e s i z e o f b l o c k A. D r o s . I n f o r m . S e r v . J32 p . 1 1 8 . +  185.  C o o p e r , K.W. (1959) Cytogenetic a n a l y s i s of major heteroc h r o m a t i c e l e m e n t s ( e s p e c i a l l y Xh and Y) i n D r o s o p h i l a m e l a n o g a s t e r and t h e t h e o r y o f h e t e r o c h r o m a t i n Chromosoma 1_0 p. 5 3 5 C r e w , F.A. and R. Lamy ( 1 9 4 0 ) Spontaneous i n v e r t e d c h a n g e b e t w e e n X and Y i n D r o s o p h i l a m e l a n o g a s t e r J . G e n e t . 22. P- 7 3 •  ex-  2  D a r l i n g t o n , C.D. (1947) Symp. S o c . E x p . B i o l . D a v i d s o n , E.H. (1976) A c a d e m i c P r e s s , New  1  N u c l e i c a c i d s and p. 2 5 2 .  Gene A c t i v i t y York.  the  i n Early  chromosomes Development.  D e m e r e c , M. and M.E. H o o v e r ( 1 9 3 9 ) . H a i r y wing--A d u p l i c a t i o n i n Drosophila melanogaster G e n e t i c s 24 p. 271. D e m e r e c , M. and H. S l i z y n s k a ( 1 9 3 7 ) of Drosophila melanogaster D o b z h a n s k y , T. ( 1 9 3 6 ) Rev. 11 p. 364.  Mottled-white 258-18 G e n e t i c s 22 p. 641.  P o s i t i o n e f f e c t s on g e n e s  Biol.  D r o n a m r a j u , K.R. (1965) The f u n c t i o n o f t h e Y-chromosome i n Man, A n i m a l s , and P l a n t s Adv. i n G e n e t . 1_3_ p. 227D u b i n i n , N.P. (1929) melanogaster  Allelomorphs B i o l . Z e n t r . 4_2  of Drosophila p. 3 2 8 .  D u b i n i n , N.P. (1929) Step a l l e l o m o r p h i s m i n Drosophil;;. melanogaster. I. Allelomorphs scute-1, scute-2, scute-3. J . E x p . B i o l . J5_ p. 5 3 D u b i n i n , N.P. (1930b) Step a l l e l o m o r p h i s m i n D r o s o p h i l a melanogaster. VI. Allelomorphs scute-7; achaete 2 - scute 10; achaete 1 - scute 11; a c h a e t e 3 - s c u t e 13. J . Exp. B i o l . 6 #3-4. D u b i n i n , N.P. (1930d) melanogaster. The scute. J . Exp. D u b i n i n , N.P. (1936) B i o l . Zhurn.  p.  Step a l l e l o m o r p h i s m i n D r o s o p h i l a t h e o r y o f c e n t r e s o f gene a c h a e t e Biol. 6 #3-7A new 851.  type  of p o s i t i o n  effect  D u b i n i n , N.P. and B.N. S i d o r o v ( 1 9 3 5 ) The p o s i t i o n o f t h e h a i r y gene B i o l . Zhurn. 4 p. 555-  effect  186.  D u b i n i n , N.P.; N.N. S o k o l o v a n d G.G. T i n i a k o r (1937) C r o s s i n g over between t h e genes " y e l l o w " , "achaete" and " s c u t e " D r o s . I n f o r m . S e r v . 8 p . 76. Ede,  D.A. (1956b) S t u d i e s o n t h e e f f e c t s o f some g e n e t i c l e t h a l f a c t o r s on t h e embryonic development o f D r o s o p h i l a melanogaster• V. A n a n a l y s i s o f t h e m u t a n t X - l 0 W i l h . Roux' A r c h . l4_2 P- 247-  Endow, S.A.; M.L. P o l a n a n d J.G. G a l l (1975) sequences o f D r o s o p h i l a melanogaster p-  665.  E p h r u s s i , B. a n d E. S u t t o n (1944) the mechanism o f p o s i t i o n e f f e c t S c i . USA 10 p . I83.  Satellite J . Mol. Biol.  A reconsideration of Proc. N a t l . Acad.  F u r m a n , D.P. a n d V.A. R a t n e r (1977) Investigation of genetic topography o f the scute l o c u s i nD r o s o p h i l a melanogaster. I I . E f f e c t o f t e m p e r a t u r e on m u t a t i o n m a n i f e s t a t i o n s o f homozygotes G e n e t i k a 1_2. #4 p . 667F u r m a n , D.P.j S.N. R o d i n a n d V.A. R a t n e r (1977a) Invest i g a t i o n o f the g e n e t i c topography o f the scute l o c u s i n D r o s o p h i l a melanogaster. I I I . E f f e c t o f temperature on maps o f t h e f u n c t i o n a l m a n i f e s t a t i o n s o f h o m o z y g o t e s G e n e t i k a 1 2 #6 p. 1042. F u r m a n , D.P.; S.N. R o d i n a n d V.A. R a t n e r (1977b) Invest i g a t i o n o f the g e n e t i c topography o f the scute l o c u s i n D r o s o p h i l a melanogaster. IV. E f f e c t o f temperature on t h e f u n c t i o n a l m a n i f e s t a t i o n o f h e t e r o z y g o t e s G e n e t i k a H #7 P- 1220. F u r m a n , D.P.j S.N. R o d i n a n d V.A. R a t n e r (1977c) Invest i g a t i o n o f the g e n e t i c topography o f the scute l o c u s i n D r o s o p h i l a melanogaster. V. Maps o f f u n c t i o n a l m a n i f e s t a t i o n s o f h e t e r o z y g o t e s and model o f t h e phenomenon G e n e t i k a 11 #8 p . 1387. F u r m a n , D.P.; S.N. R o d i n a n d V.A. R a t n e r (1979) ' Structural and f u n c t i o n a l a n a l y s i s o f t h e s c u t e l o c u s i n D r o s o p h i l a melanogaster T h e o r . A p p l . G e n e t . _J?J5 P 231#  G a l l , J . (1973) R e p e t i t i v e DNA i n D r o s o p h i l a M o l e c u l a r • : Cytogenetics, B.A. H a m k a l a a n d J . P a p a c o n s t a n t i n o u ( e d s . ) Ptenum P r e s s , New Y o r k p . 59* G a r c i a - B e l l i d o , A. (1979) Genetic a n a l y s i s o f the achaetescute system o f D r o s o p h i l a melanogaster G e n e t i c s 91 p. 491.  187.  G a r c i a - B e l l i d o , A. a n d J.R. M e r r i a m (1969) C e l l lineage o f the i m a g i n a l d i s k s i n D r o s o p h i l a gynandromorphs J . Exp. Z o o l . 1 7 0 p. 6 1 . G a r c i a - B e l l i d o , A. a n d J.R. M e r r i a m ( 1 9 7 1 a ) Parameters o f the wing i m a g i n a l d i s c development o f D r o s o p h i l a melanogaster Dev. B i o l . 2 4 p. 6 1 . 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S m i r n o v a (1980) Investigation of m a t e r n a l e f f e c t f o r genes c o d i n g f o r 6-phosphogluconate dehydrogenase and g l u c o s e - 6 - p h o s p h a t e dehydrogenase i n Drosophila melanogaster G e n e t i k a 1_6 p . 5 5 • G e r s h , E.S. (194-9) I n f l u e n c e o f t e m p e r a t u r e on t h e e x p r e s s i o n o f p o s i t i o n e f f e c t s i n the scute-8 stock o f D r o s o p h i l a melanogaster and i t s r e l a t i o n t o h e t e r o c h r o matization G e n e t i c s ^4 p . 7 0 1 . G e r s h , E.S. ( 1 9 5 1 ) P i g m e n t a t i o n i n a m o t t l e d w h i t e eye due t o p o s i t i o n e f f e c t i n D r o s o p h i l a m e l a n o g a s t e r G e n e t i c s 21 P- 3 ' 2  2  G e r s h , E.S. (I963) V a r i e g a t i o n a t the white locus i n Drosophila melanogaster D.I.S. 22. P- 8 1 . G e r s h , E. a n d B. 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Z u c k e r k a n d l , E. (197*0 A possible role of "inert" heterochromatin i n c e l l d i f f e r e n t i a t i o n . A c t i o n o f a n d comp e t i t i o n f o r "locking" molecules. B i o c h i m i e J56 p. 9 3 7 -  

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