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Perspective:Sign Epistasis and Genetic Constraint on Evolutionary Trajectories

Perspective:Sign Epistasis and Genetic Constraint on Evolutionary Trajectories
Perspective:Sign Epistasis and Genetic Constraint on Evolutionary Trajectories
Epistasis for fitness means that the selective effect of a mutation is conditional on the genetic background in which it appears. Although epistasis is widely observed in nature, our understanding of its consequences for evolution by natural selection remains incomplete. In particular, much attention focuses only on its influence on the instantaneous rate of changes in frequency of selected alleles via epistatic contribution to the additive genetic variance for fitness. Thus, in this framework epistasis only has evolutionary importance if the interacting loci are simultaneously segregating in the population. However, the selective accessibility of mutational trajectories to high fitness genotypes may depend on the genetic background in which novel mutations appear, and this effect is independent of population polymorphism at other loci. Here we explore this second influence of epistasis on evolution by natural selection. We show that it is the consequence of a particular form of epistasis, which we designate sign epistasis. Sign epistasis means that the sign of the fitness effect of a mutation is under epistatic control; thus, such a mutation is beneficial on some genetic backgrounds and deleterious on others. Recent experimental innovations in microbial systems now permit assessment of the fitness effects of individual mutations on multiple genetic backgrounds. We review this literature and identify many examples of sign epistasis, and we suggest that the implications of these results may generalize to other organisms. These theoretical and empirical considerations imply that strong genetic constraint on the selective accessibility of trajectories to high fitness genotypes may exist and suggest specific areas of investigation for future research.
Compensatory mutations, Fisher, functional epistasis, genetic recombination, statistical epistasis, Wright's fitness landscape
0014-3820
1165-1174
Weinreich, Daniel M.
a5522cf4-5a31-4e13-9934-e3529fdd4d6f
Watson, Richard A.
ce199dfc-d5d4-4edf-bd7b-f9e224c96c75
Chao, Lin
620948c9-b885-44a0-8e61-0610a799c90d
Weinreich, Daniel M.
a5522cf4-5a31-4e13-9934-e3529fdd4d6f
Watson, Richard A.
ce199dfc-d5d4-4edf-bd7b-f9e224c96c75
Chao, Lin
620948c9-b885-44a0-8e61-0610a799c90d

Weinreich, Daniel M., Watson, Richard A. and Chao, Lin (2005) Perspective:Sign Epistasis and Genetic Constraint on Evolutionary Trajectories Evolution, 59, (6), pp. 1165-1174.

Record type: Article

Abstract

Epistasis for fitness means that the selective effect of a mutation is conditional on the genetic background in which it appears. Although epistasis is widely observed in nature, our understanding of its consequences for evolution by natural selection remains incomplete. In particular, much attention focuses only on its influence on the instantaneous rate of changes in frequency of selected alleles via epistatic contribution to the additive genetic variance for fitness. Thus, in this framework epistasis only has evolutionary importance if the interacting loci are simultaneously segregating in the population. However, the selective accessibility of mutational trajectories to high fitness genotypes may depend on the genetic background in which novel mutations appear, and this effect is independent of population polymorphism at other loci. Here we explore this second influence of epistasis on evolution by natural selection. We show that it is the consequence of a particular form of epistasis, which we designate sign epistasis. Sign epistasis means that the sign of the fitness effect of a mutation is under epistatic control; thus, such a mutation is beneficial on some genetic backgrounds and deleterious on others. Recent experimental innovations in microbial systems now permit assessment of the fitness effects of individual mutations on multiple genetic backgrounds. We review this literature and identify many examples of sign epistasis, and we suggest that the implications of these results may generalize to other organisms. These theoretical and empirical considerations imply that strong genetic constraint on the selective accessibility of trajectories to high fitness genotypes may exist and suggest specific areas of investigation for future research.

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Published date: 2005
Keywords: Compensatory mutations, Fisher, functional epistasis, genetic recombination, statistical epistasis, Wright's fitness landscape
Organisations: Agents, Interactions & Complexity

Identifiers

Local EPrints ID: 261612
URI: http://eprints.soton.ac.uk/id/eprint/261612
ISSN: 0014-3820
PURE UUID: 7b0fbd97-f771-4457-99d5-c947ddc1eabd

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Date deposited: 30 Nov 2005
Last modified: 18 Jul 2017 09:00

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Contributors

Author: Daniel M. Weinreich
Author: Lin Chao

University divisions

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