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Curr Opin Genet Dev. 2013 Dec;23(6):700-7. doi: 10.1016/j.gde.2013.10.007. Epub 2013 Nov 27.

Should evolutionary geneticists worry about higher-order epistasis?

Author information

1
Department of Ecology and Evolutionary Biology, and Center for Computational Molecular Biology, Brown University, Box G-W, Providence, RI 02912, USA. Electronic address: Daniel_Weinreich@Brown.edu.

Abstract

Natural selection drives evolving populations up the fitness landscape, the projection from nucleotide sequence space to organismal reproductive success. While it has long been appreciated that topographic complexities on fitness landscapes can arise only as a consequence of epistatic interactions between mutations, evolutionary genetics has mainly focused on epistasis between pairs of mutations. Here we propose a generalization to the classical population genetic treatment of pairwise epistasis that yields expressions for epistasis among arbitrary subsets of mutations of all orders (pairwise, three-way, etc.). Our approach reveals substantial higher-order epistasis in almost every published fitness landscape. Furthermore we demonstrate that higher-order epistasis is critically important in two systems we know best. We conclude that higher-order epistasis deserves empirical and theoretical attention from evolutionary geneticists.

PMID:
24290990
PMCID:
PMC4313208
DOI:
10.1016/j.gde.2013.10.007
[Indexed for MEDLINE]
Free PMC Article

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