Cellular effects and epistasis among three determinants of adaptation in experimental populations of Saccharomyces cerevisiae

Eukaryot Cell. 2011 Oct;10(10):1348-56. doi: 10.1128/EC.05083-11. Epub 2011 Aug 19.


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 replicate Saccharomyces cerevisiae populations propagated in two different environments, a low-glucose and a high-salt environment. In a low-glucose environment, MDS3e and MKT1e interacted positively to confer a fitness advantage. Also, PMA1e from a high-salt environment interacted negatively with MKT1e in a low-glucose environment, an example of a Dobzhansky-Muller incompatibility that confers reproductive isolation. Here we showed that the negative interaction between PMA1e and MKT1e is mediated by alterations in intracellular pH, while the positive interaction between MDS3e and MKT1e 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 the MDS3 mutation is a necessary condition for the spread and fixation of the new mutations at the identical site in MKT1. The expected mutations in MKT1 rose to high frequencies in two of three experimental populations carrying MDS3e 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.

MeSH terms

  • Adaptation, Physiological*
  • Alleles
  • Epistasis, Genetic*
  • Gene Expression Regulation, Fungal
  • Glucose / metabolism
  • Hydrogen-Ion Concentration
  • Mutation
  • Proton-Translocating ATPases / genetics*
  • Proton-Translocating ATPases / metabolism
  • Repressor Proteins / genetics*
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / chemistry
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism


  • MDS3 protein, S cerevisiae
  • MKT1 protein, S cerevisiae
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • PMA1 protein, S cerevisiae
  • Proton-Translocating ATPases
  • Glucose