Widespread Genetic Incompatibilities between First-Step Mutations during Parallel Adaptation of Saccharomyces cerevisiae to a Common Environment

Abstract

Independently evolving populations may adapt to similar selection pressures via different genetic changes. The interactions between such changes, such as in a hybrid individual, can inform us about what course adaptation may follow and allow us to determine whether gene flow would be facilitated or hampered following secondary contact. We used Saccharomyces cerevisiae to measure the genetic interactions between first-step mutations that independently evolved in the same biosynthetic pathway following exposure to the fungicide nystatin. We found that genetic interactions are prevalent and predominantly negative, with the majority of mutations causing lower growth when combined in a double mutant than when alone as a single mutant (sign epistasis). The prevalence of sign epistasis is surprising given the small number of mutations tested and runs counter to expectations for mutations arising in a single biosynthetic pathway in the face of a simple selective pressure. Furthermore, in one third of pairwise interactions, the double mutant grew less well than either single mutant (reciprocal sign epistasis). The observation of reciprocal sign epistasis among these first adaptive mutations arising in the same genetic background indicates that partial postzygotic reproductive isolation could evolve rapidly between populations under similar selective pressures, even with only a single genetic change in each. The nature of the epistatic relationships was sensitive, however, to the level of drug stress in the assay conditions, as many double mutants became fitter than the single mutants at higher concentrations of nystatin. We discuss the implications of these results both for our understanding of epistatic interactions among beneficial mutations in the same biochemical pathway and for speciation.

Abstract

A study of yeast adapted to the fungicide nystatin finds that the first step toward speciation (partial postzygotic reproductive isolation) can evolve rapidly in populations under similar selective pressures.

Author Summary

We crossed yeast bearing different genetic mutations to determine the fitness of their hybrid offspring. These strains had previously evolved in the presence of the fungicide nystatin. Even though the initial strains had nearly identical genomes, differing only in the mutation they carried within the biosynthetic pathway leading to ergosterol, the hybrid offspring were less fit than expected based on parental fitness. These negative interactions were so strong that beneficial mutations often became deleterious in the presence of one another (sign epistasis). In one third of crosses, the hybrid double mutant grew less well than either single mutant (reciprocal sign epistasis). This work indicates that the first step toward speciation, partial postzygotic reproductive isolation, can evolve rapidly between populations under similar selective pressures, even with only a single genetic change in each.