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Physical constraints on epistasis in proteins and gene regulatory networks Murugan, Arvind
Description
Living systems evolve one mutation at a time, but a single mutation can alter the effect of subsequent mutations. The underlying mechanistic determinants of such epistasis are unclear. Here, we argue that the physical properties of a biological system can generically and easily constrain its epistasis. We analyze the interaction between mutations in generic models of proteins and biochemical networks. In each case, a slow, collective physical mode is actuated upon mutation, reducing the dimensionality of mutational effects and thus the rank of the epistatic matrix. This, in turn, reduces the ruggedness of the sequence-to-function map. By providing a mechanistic basis for experimentally observed global epistasis, these results suggest that slow collective physical modes can make biological systems more evolvable.Â
Item Metadata
Title |
Physical constraints on epistasis in proteins and gene regulatory networks
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Creator | |
Publisher |
Banff International Research Station for Mathematical Innovation and Discovery
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Date Issued |
2019-08-21T12:25
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Description |
Living systems evolve one mutation at a time, but a single mutation can alter the effect of subsequent mutations. The underlying mechanistic determinants of such epistasis are unclear. Here, we argue that the physical properties of a biological system can generically and easily constrain its epistasis. We analyze the interaction between mutations in generic models of proteins and biochemical networks. In each case, a slow, collective physical mode is actuated upon mutation, reducing the dimensionality of mutational effects and thus the rank of the epistatic matrix. This, in turn, reduces the ruggedness of the sequence-to-function map. By providing a mechanistic basis for experimentally observed global epistasis, these results suggest that slow collective physical modes can make biological systems more evolvable.Â
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Extent |
33.0 minutes
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Type | |
File Format |
video/mp4
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Language |
eng
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Notes |
Author affiliation: University of Chicago
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Series | |
Date Available |
2021-01-18
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivatives 4.0 International
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DOI |
10.14288/1.0395645
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URI | |
Affiliation | |
Peer Review Status |
Unreviewed
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Scholarly Level |
Researcher
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Aggregated Source Repository |
DSpace
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Item Citations and Data
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International