The polygenic basis of an ancient divergence in yeast thermotolerance

Some of the most unique and compelling survival strategies in the natural world evolved long ago, and are fixed in now-isolated species. Molecular insight into these adaptations has been limited, as classic experimental genetics has focused on the interfertile individuals of a population. Here we dissect a complex thermotolerance difference between yeast species that diverged millions of years ago. Using a new mapping approach that screens mutants in a sterile interspecific hybrid, we identified eight genes that underlie the growth advantage of Saccharomyces cerevisiae over its sister species S. paradoxus at high temperature. All eight encode housekeeping factors with no known direct function in heat-shock or stress response. Pro-thermotolerance alleles at these mapped loci were required for the adaptive trait in S. cerevisiae and sufficient for its partial reconstruction in S. paradoxus. Together, our data reveal the genetic mechanism by which S. cerevisiae acquired its high-temperature growth advantage in the distant past. And our study lays the groundwork for the mapping of genotype to phenotype in clades of sister species across Eukarya.