Simon Update: Yeast Interactions

The importance of genetic interactions (epistasis) in the genetic architecture of complex traits has been a source of controversy since the early days of quantitative genetics. On the one hand, there are many examples where epistasis has been shown to have very large effects on individual phenotypes. On the other hand, both theory and previous observations suggests that the additive genetic variance dwarfs the epistatic genetic variance.

In a large cross (n = 4390) between two strains of yeast, we identified large epistatic networks for 20 complex traits. The networks were largely centered on a number of hub-loci and altogether involved hundreds of genetic interactions. Most network hubs had the ability to either suppress or uncover the phenotypic effects of other loci. Many multi-locus allele combinations resulted in phenotypes that deviated substantially from the expectations, had the loci acted in an additive manner.

Despite the strong epistatic effects of certain multi-locus allele combinations, the majority of the genetic variance was additive. This illustrates how the contrasting views described above are in fact compatible with each other, and that the level of epistatic variance is a poor indicator of the genetic architecture. Using simulations, we also illustrate how the additive variance explained by individual loci were highly dependent on the genetic background.

This study highlights the importance of accounting for epistasis in order to predict individual phenotypes. It also shows how a population can harbor considerable cryptic/hidden genetic potential, which might have implications for breeding efforts.