Genetics. Published Articles Ahead of Print: August 24, 2007, Copyright © 2007
doi:10.1534/genetics.107.075812


A more recent version of this article appeared on October 1, 2007.


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Evolution Can Favor Antagonistic Epistasis

1 Princeton University
2 Stanford University

* To whom correspondence should be addressed. E-mail: mmdesai{at}princeton.edu.

Submitted on May 10, 2007
Revised on June 9, 2007
Accepted on 8 August 2007


Abstract

The accumulation of deleterious mutations plays a major role in evolution, and key to this are the interactions between their fitness effects, known as epistasis. Whether mutations tend to interact synergistically (with multiple mutations being more deleterious than would be expected from their individual fitness effects) or antagonistically is important for a variety of evolutionary questions, particularly the evolution of sex. Unfortunately, the experimental evidence on the prevalence and strength of epistasis is mixed and inconclusive. Here we study theoretically whether synergistic or antagonistic epistasis is likely to be favored by evolution, and by how much. We find that in the presence of recombination, evolution favors less synergistic or more antagonistic epistasis whenever mutations that change the epistasis in this direction are possible. This is because evolution favors increased buffering between the effects of deleterious mutations. This suggests that we should not expect synergistic epistasis to be widespread in nature, and hence that the mutational deterministic hypothesis for the advantage of sex may not apply widely.

Key Words: Antagonistic Epistasis, Evolution of Epistasis, Mutational Robustness