Modulating Crossover Frequency and Interference for Obligate Crossovers in Meiosis.

Meiotic crossover frequencies show wide variation among organisms. But most organisms maintain at least one crossover per homolog pair (obligate crossover). In , previous studies have shown crossover frequencies are reduced in the mismatch repair related mutant Δ and enhanced in a meiotic checkpoint mutant Δ by up to twofold at specific chromosomal loci, but both mutants maintain high spore viability. We analyzed meiotic recombination events genome-wide in Δ, Δ, and Δ Δ mutants to test the effect of variation in crossover frequency on obligate crossovers. Δ showed ∼30% genome-wide reduction in crossovers (64 crossovers per meiosis) and loss of the obligate crossover, but nonexchange chromosomes were efficiently segregated. Δ showed ∼50% genome-wide increase in crossover frequency (137 crossovers per meiosis), elevated noncrossovers as well as loss of chromosome size dependent double-strand break formation. Meiotic defects associated with did not cause significant increase in nonexchange chromosome frequency. Crossovers were restored to wild-type frequency in the double mutant Δ Δ (100 crossovers per meiosis), but obligate crossovers were compromised. Genetic interference was reduced in Δ, Δ, and Δ Δ. Triple mutant analysis of Δ Δ with other resolvase mutants showed that most of the crossovers in Δ Δ are made through the Mus81-Mms4 pathway. These results are consistent with a requirement for increased crossover frequencies in the absence of genetic interference for obligate crossovers. In conclusion, these data suggest crossover frequencies and the strength of genetic interference in an organism are mutually optimized to ensure obligate crossovers.