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.

Convergent adaptation to dangerous prey proceeds through the same first‐step mutation in the garter snake Thamnophis sirtalis

“…In extreme cases, sign epistasis can cause a single substitution to have opposing functional or fitness consequences in different genetic backgrounds Harms and Thornton 2013;Shah et al 2015;Storz 2016;Ono et al 2017). Unlike our results, Natarajan et al (2015Natarajan et al ( , 2016 found that convergence in hemoglobin-oxygen affinity in high-altitude avian species did not evolve through a repeated order of mutations to hemoglobin.…”

Analysis of RPA190 revealed multiple positively selected mutations associated with metalaxyl resistance in Phytophthora infestans

“…This also supports the observation of moderate metalaxyl resistance in P. infestans F1 progeny from a cross between sensitive and highly resistant isolates . It has been reported that double mutations of yeast showed greater fitness than single or no mutation isolates in the presence of fungicide . Although the role of the corresponding mutations was not investigated in all organisms, different mutations of RPA190 in yeast did lead to different phenotypes such as N1203S and L1222S .…”

Parallel genetic evolution and speciation from standing variation

“…; and Ono et al. for discussion of environment‐specific hybrid incompatibilities). We consider our model to be one of “extrinsic” rather than “intrinsic” isolation because we do not consider traits such as gamete viability, which experience environment‐independent selection.…”