Meiotic crossover frequencies show wide variation among organisms. But most organisms maintain at least one crossover per homolog pair (obligate crossover). In S. cerevisiae, previous studies have shown crossover frequencies are reduced in the mismatch repair related mutant mlh3 delta and enhanced in a meiotic checkpoint mutant pch2 delta by up to two-fold at specific chromosomal loci, but both mutants maintain high spore viability. We analyzed meiotic recombination events genome wide in mlh3 delta, pch2 delta and mlh3pch2 delta mutants to test the effect of variation in crossover frequency on obligate crossovers.
mlh3 delta showed 1.5 fold genome wide reduction in crossovers (64 crossovers per meiosis) and loss of the obligate crossover, but non-exchange chromosomes were efficiently segregated. pch2 delta showed 1.5 fold genome-wide increase in crossover frequency (136 crossovers per meiosis) as well as elevated non-crossovers. Obligate crossovers were maintained in pch2 delta, suggesting that meiotic defects associated with pch2 delta do not increase non-exchange chromosome frequency. Crossovers were restored to wild-type frequency in the double mutant mlh3pch2 delta (100 crossovers per meiosis) but obligate crossovers were compromised. Triple mutant analysis of mlh3pch2 delta with other resolvase mutants showed that most of the crossovers in mlh3pch2 delta are made through the Mms4-Mus81 pathway. Genetic interference was reduced in mlh3 delta, pch2 delta and mlh3pch2 delta. Non-exchange chromosomes were observed among four spore viable tetrads at low frequencies in wild type and pch2 delta but elevated in mlh3 delta and mlh3pch2 delta.
The pch2 delta mutant data support previous computational analysis showing that increased crossover frequencies are required in the absence of genetic interference for obligate crossovers. Although, the mlh3pch2 delta mutant made as many crossovers as wild type, the percentage of meioses with non-exchange events were significantly more than wild type. These results suggest crossover frequencies in an organism are optimized based on the strength of genetic interference to ensure obligate crossovers. Less...