The mismatch repair system is the major barrier to genetic recombination during interspecific sexual conjugation in prokaryotes. The existence of this anti‐recombination activity has implications for theories of evolution and the isolation of species. To determine if this phenomenon occurs in eukaryotes, the effect of a deficiency of mismatch repair on the meiotic sterility of an interspecific hybrid of Saccharomyces cerevisiae and the closely related species Saccharomyces paradoxus was examined. The results demonstrate that the rare viable spores from these hybrids have high frequencies of aneuploidy and low frequencies of genetic exchange. Hybrids lacking mismatch repair genes PMS1 or MSH2 display increased meiotic recombination, decreased chromosome non‐disjunction and improved spore viability. These observations are consistent with the proposal that the mismatch repair system is an element of the genetic barrier between eukaryotic species. We suggest that an anti‐recombination activity during meiosis contributes towards the establishment of post‐zygotic species barriers.

Topoisomerase II (topo II) catalyzes the decatenation of interlinked DNA molecules and is essential for chromosome segregation. To test the hypothesis that the noncatalytic C-terminal domain of topo II is necessary for mediating interactions with other proteins required for chromosome segregation, we used a two-hybrid cloning strategy to identify proteins that interact with S. cerevisiae topo II in vivo. One protein identified (Sgs1p) is structurally related to E. coli RecQ protein and contains helicase signature motifs. Strains lacking Sgs1p exhibit elevated levels of chromosome misseggregation during both mitotic and meiotic division. We propose a model to account for the interaction of a topoisomerase and a helicase in the faithful segregation of newly replicated eukaryotic chromosomes.

The question of how genetic variation in a population influences phenotypic variation and evolution is of major importance in modern biology. Yet much is still unknown about the relative functional importance of different forms of genome variation and how they are shaped by evolutionary processes. Here we address these questions by population level sequencing of 42 strains from the budding yeast Saccharomyces cerevisiae and its closest relative S. paradoxus. We find that genome content variation, in the form of presence or absence as well as copy number of genetic material, is higher within S. cerevisiae than within S. paradoxus, despite genetic distances as measured in single-nucleotide polymorphisms being vastly smaller within the former species. This genome content variation, as well as loss-of-function variation in the form of premature stop codons and frameshifting indels, is heavily enriched in the subtelomeres, strongly reinforcing the relevance of these regions to functional evolution. Genes affected by these likely functional forms of variation are enriched for functions mediating interaction with the external environment (sugar transport and metabolism, flocculation, metal transport, and metabolism). Our results and analyses provide a comprehensive view of genomic diversity in budding yeast and expose surprising and pronounced differences between the variation within S. cerevisiae and that within S. paradoxus. We also believe that the sequence data and de novo assemblies will constitute a useful resource for further evolutionary and population genomics studies.