Why epistasis is important for selection and adaptation

Organisms are built from thousands of genes that interact in complex ways. Still, the mathematical theory of evolution is dominated by a gene-by-gene perspective in which genes are assumed to have the same effects regardless of genetic background. Gene interaction, or epistasis, plays a role in some theoretical developments such as the evolution of recombination, reproductive isolation, and canalization, but is strikingly missing from our standard accounts of phenotypic adaptation. This absence is most puzzling within the field of quantitative genetics, which, despite its polygenic perspective and elaborate statistical representation of epistasis, has not found a single important role for gene interaction in evolution. To the contrary, there is a widespread consensus that epistasis is evolutionary inert, and that all we need to know to predict evolutionary dynamics is the additive component of the genetic variance. This view may have roots in convenience, but also in theoretical results showing that the response to selection derived from epistatic variance components is not permanent and will decay when selection is relaxed. I show that these results are tied to a conceptual confusion, and are misleading as general statements about the significance of epistasis for the selection response and adaptation.