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Evidence for in vitro and in vivo molecular "Darwinian" selection Rank, Gerald Henry

Abstract

Molecular "Darwinian" selection is initially defined as the generation of a variant molecule, within a population of self-replicating molecules, that becomes the predominant molecular form in descendent populations by virtue of its replicative superiority. The molecular biology of the replication of Qβ in vivo is presented prior to providing evidence for molecular "Darwinian" selection of Qβ-RNA in vitro. Critical experiments undertaken to prove that Qβ—replicase is capable of catalyzing the synthesis of molecular replicas of primer Qβ-RNA in vitro are described. This information is followed by a description of the experiments utilized to demonstrate the occurrence of molecular "Darwinian" selection of Qβ-RNA under different selective environments. Molecular and phenotypic properties of mutant RNA molecules are discussed. After an account of the expectations of molecular "Darwinian" selection in vivo: suppressitivity, gross alterations of DNA base composition in microorganisms' and the von Magnus effect are presented as evidence for molecular "Darwinian" selection in vivo. Suppressive respiratory-deficiency in Saccharomyces cerevisiae is taken as a model system for the investigation of suppressitivity. A literature review of the data generated by genetic and cytological analyses of suppressitivity was found to be accommodated by the hypothesis of molecular "Darwinian" selection in vivo. In addition, the author's genetic analyses of: (i) mosaic colonies, (ii) the effect of the cytoplasmically-inherited suppressive-factor on a cytoplasmically-inherited erythromycin-resistant marker, and (iii) high and low suppressitivity, were interpreted as evidence for the hypothesis. Biochemical evidence is presented that indicates that the suppressive-factor is an abnormal mitochondrial DNA with a replicative superiority to normal mitochondrial DNA. A brief discussion of the possible influence of molecular "Darwinian" selection on pre and post cellular evolution is presented.

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