Variation in Crossover Frequencies Perturb Crossover Assurance Without Affecting Meiotic Chromosome Segregation in Saccharomyces cerevisiae

摘要

The segregation of homologous chromosomes during the Meiosis I division requires an obligate crossover per homolog pair (crossover assurance). In Saccharomyces cerevisiae and mammals, [Msh4][1] and [Msh5][2] proteins stabilize Holliday junctions and its progenitors to facilitate crossing over. S. cerevisiae [msh4][1]/5 hypomorphs that reduce crossover levels up to twofold at specific loci on chromosomes VII, VIII, and XV without affecting homolog segregation were identified recently. We use the [msh4][1]–R676W hypomorph to ask if the obligate crossover is insulated from variation in crossover frequencies, using a S . cerevisiae S288c/YJM789 hybrid to map recombination genome-wide. The [msh4][1]–R676W hypomorph made on average 64 crossovers per meiosis compared to 94 made in wild type and 49 in the [msh4][1]Δ mutant confirming the defect seen at individual loci on a genome-wide scale. Crossover reductions in [msh4][1]–R676W and [msh4][1]Δ were significant across chromosomes regardless of size, unlike previous observations made at specific loci. The [msh4][1]–R676W hypomorph showed reduced crossover interference. Although crossover reduction in [msh4][1]–R676W is modest, 42% of the four viable spore tetrads showed nonexchange chromosomes. These results, along with modeling of crossover distribution, suggest the significant reduction in crossovers across chromosomes and the loss of interference compromises the obligate crossover in the [msh4][1] hypomorph. The high spore viability of the [msh4][1] hypomorph is maintained by efficient segregation of the natural nonexchange chromosomes. Our results suggest that variation in crossover frequencies can compromise the obligate crossover and also support a mechanistic role for interference in obligate crossover formation. [1]: http://www.yeastgenome.org/cgi-bin/locus.fpl?dbid=S000001891 [2]: http://www.yeastgenome.org/cgi-bin/locus.fpl?dbid=S000002313