Originally published as Genetics Published Articles Ahead of Print on August 24, 2007.

Genetics, Vol. 177, 1001-1010, October 2007, Copyright © 2007
doi:10.1534/genetics.107.075812

Evolution Can Favor Antagonistic Epistasis

Michael M. Desai*,1, Daniel Weissman{dagger} and Marcus W. Feldman{dagger}

* Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544 and {dagger} Department of Biological Sciences, Stanford University, Stanford, California 94305

1 Corresponding author: Lewis-Sigler Institute for Integrative Genomics, Carl Icahn Laboratory, Princeton University, Princeton, NJ 08544.
E-mail: mmdesai{at}princeton.edu

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 against 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.


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Genetics 2007 177: NP. [Full Text]