PT - JOURNAL ARTICLE AU - Tim J. Cooper AU - Margaret R. Crawford AU - Laura J. Hunt AU - Marie-Claude Marsolier-Kergoat AU - Bertrand Llorente AU - Matthew J. Neale TI - Mismatch repair impedes meiotic crossover interference AID - 10.1101/480418 DP - 2018 Jan 01 TA - bioRxiv PG - 480418 4099 - http://biorxiv.org/content/early/2018/11/27/480418.1.short 4100 - http://biorxiv.org/content/early/2018/11/27/480418.1.full AB - Sequence divergence, mediated by the anti-recombinogenic activity of mismatch repair (MMR), forms a potent barrier to meiotic recombination and in turn the formation of viable gametes1–5. However, exactly how MMR jeopardizes meiotic success is unclear. Here we utilize a combination of S. cerevisiae genetics, genome-wide mapping of recombination and computational modelling to demonstrate that MMR unexpectedly influences the global distribution of recombination through preferential suppression of interfering crossovers (COs) at regions of greater sequence divergence. As a result, inactivation of MMR not only increases the rate of recombination, as previously observed, but also, paradoxically, the strength of CO interference. Our observations reveal a new mechanism by which MMR spatially sculpts the meiotic landscape—linking CO control to the mechanisms that can reproductively isolate a population, and highlighting how genomes may become meiotically incompatible at the molecular level, dependent upon interactions of the primary DNA sequence.