Cellular Effects and Epistasis among Three Determinants of Adaptation in Experimental Populations of Saccharomyces cerevisiae

Epistatic interactions in which the phenotypic effect of an allele is conditional on its genetic background have been shown to play a central part in various evolutionary processes. In a previous study (J. B. Anderson et al., Curr. Biol. 20:1383-1388, 2010; J. R. Dettman, C. Sirjusingh, L. M. Kohn, and J. B. Anderson, Nature 447:585-588, 2007), beginning with a common ancestor, we identified three determinants of fitness as mutant alleles (each designated with the letter “e ”) that arose in replicateSaccharomyces cerevisiae populations propagated in two different environments, a low-glucose and a high-salt environment. In a low-glucose environment,MDS3e andMKT1e interacted positively to confer a fitness advantage. Also,PMA1e from a high-salt environment interacted negatively withMKT1e in a low-glucose environment, an example of a Dobzhansky-Muller incompatibility that confers reproductive isolation. Here we showed that the negative interaction betweenPMA1e andMKT1e is mediated by alterations in intracellular pH, while the positive interaction betweenMDS3e andMKT1e is mediated by changes in gene expression affecting glucose transporter genes. We specifically addressed the evolutionary significance of the positive interaction by showing that the presence of theMDS3 mutation is a necessary condition for the spread and fixation of the new mutations at the identical site inMKT1 . The expected mutations inMKT1 rose to high frequencies in two of three experimental populations carryingMDS3e but not in any of three populations carrying the ancestral allele. These data show how positive and negative epistasis can contribute to adaptation and reproductive isolation.