Determinants of divergent adaptation and Dobzhansky-Muller interaction in experimental yeast populations

Divergent adaptation can be associated with reproductive isolation in the process of speciation. We recently demonstrated the link between divergent adaptation and the onset of reproductive isolation in experimental populations of the yeast Saccharomyces cerevisiae evolved from a single progenitor in either a high-salt or a low-glucose environment. However, the genetic basis for adaptation and reproductive isolation remained unknown in this system. Here, we use whole-genome re-sequencing of representatives of three populations to identify 15 candidate mutations, six of which explained the adaptive increases in mitotic fitness in the two environments. In two populations evolved in high salt, two different mutations occurred in the proton efflux pump gene PMA1 and the global transcriptional repressor gene CYC8; the ENA genes encoding sodium efflux pumps were over-expressed once through expansion of this gene cluster and once as a result of the mutation in the regulator CYC8. In the population from low glucose, one mutation occurred in MDS3, which modulates growth at high pH, and one in MKT1, a global regulator of mRNAs encoding mitochondrial proteins, the latter recapitulating a naturally-occurring variant. A Dobzhansky-Muller (DM) incompatibility between the evolved alleles of PMA1 and MKT1 strongly depressed fitness in the low-glucose environment. This DM interaction is the first reported between experimentally evolved alleles of known genes and shows how reproductive isolation can arise rapidly when divergent selection is strong. Evolved and progenitor strains were grown in stressed and unstressed conditions to identify role of mutations in gene expression.