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Perspective:Sign Epistasis and Genetic Constraint on Evolutionary Trajectories

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

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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.

Item Type:Article
Creator/Authors:
Daniel M. Weinreich
Richard A. Watson
Lin Chao
Keywords:Compensatory mutations, Fisher, functional epistasis, genetic recombination, statistical epistasis, Wright's fitness landscape
Research Group:Old ECS Groups > BIO@ECS Research Group
Old ECS Groups > Science and Engineering of Natural Systems
Current ECS Groups > Agents, Interaction and Complexity
Date:2005
Information about this record:
Performance Indicator:EZ~03~01~11
Citations:ISI: 124, Google Scholar: 64
Downloads (2010):141
ID Code:11612
Last Modified:23 Sep 2011 10:32
Deposited On:30 Nov 2005 by Watson, Richard

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