Mismatch repair disturbs meiotic crossover control in S. cerevisiae

Crossover formation during meiosis generates genetic diversity. In many species most crossovers display interference, meaning they are spaced more evenly than expected by chance, and are called class I crossovers. Class II crossovers, a minority pathway, are believed to lack substantial interference. Here, using whole-genome recombination maps, we examine the impact of mismatch repair (MMR) on the formation and distribution of crossovers in Saccharomyces cerevisiae. Loss of the MMR protein Msh2 increases the uniformity of crossover distributions-an effect that is independent of changes in crossover frequency. Simulations indicate that this effect is driven by increases in the class I crossover proportion without any change in interference strength. Consistent with this view, distributions of Zip3 foci, specific markers of class I crossovers, are unchanged by MSH2 deletion. Notably, in wild-type cells, fewer crossovers arise in regions of higher polymorphism density-a skew that depends on both Msh2 and Zip3. Taken together, our results indicate a dual influence of Msh2 on recombination: suppression of class I crossovers in regions of higher polymorphism density, whilst unexpectedly promoting class II crossover formation. Our findings highlight how MMR shapes the landscape of genetic exchange, and links recombination to sequence divergence and its role in speciation.