Interference (genetic)

Abstract: Meiotic recombination plays a central role in the evolution of sexually reproducing organisms. The two recombination outcomes, crossover (CO) and noncrossover (NCO), increase genetic diversity, but have the potential to homogenize alleles by gene conversion. While CO rates are known to vary considerably across the genome, NCOs and gene conversions have only been identified in a handful of loci. To examine recombination genome-wide and at high spatial resolution, we generated maps of COs, CO-associated gene conversion and NCO gene conversion using dense genetic marker data collected from all four products of 56 yeast meioses. Our maps reveal differences in the distributions of COs and NCOs, showing more regions where either COs or NCOs are favoured than expected by chance. Furthermore, we detect evidence for interference between COs and NCOs, a phenomenon previously only known to occur between COs. Up to 1% of the genome of each meiotic product is subject to gene conversion in a single meiosis, with detectable bias towards GC nucleotides. The maps represent the first high-resolution, genome-wide characterization of the multiple outcomes of recombination in any organism. In addition, because NCO hot spots create holes of reduced linkage within haplotype blocks, our results stress the need to incorporate NCOs into genetic linkage analysis.

Abstract: Current models for meiotic recombination require that crossovers derive from the resolution of a double-Holliday junction (dHJ) intermediate In prokaryotes, enzymes responsible for HJ resolution are well characterized but the identification of a eukaryotic nuclear HJ resolvase has been elusive Indirect evidence suggests that MUS81 from humans and fission yeast encodes a HJ resolvase We provide three lines of evidence that Mus81/Mms4 is not the major meiotic HJ resolvase in S cerevisiae: (1) MUS81/MMS4 is required to form only a distinct subset of crossovers; (2) rather than accumulating, dHJ intermediates are reduced in an mms4 mutant; and (3) expression of a bacterial HJ resolvase has no suppressive effect on mus81 meiotic phenotypes Our analysis also reveals the existence of two distinct classes of crossovers in budding yeast Class I is dependent upon MSH4/MSH5 and exhibits crossover interference, while class II is dependent upon MUS81/MMS4 and exhibits no interference mms4 specifically reduces crossing over on small chromosomes, which are known to undergo less interference The correlation between recombination rate and degree of interference to chromosome size may therefore be achieved by modulating the balance between class I/class II crossovers