Variation in crossover frequencies perturb crossover assurance without affecting meiotic chromosome segregation in Saccharomyces cerevisiae.
Bottom Line: Crossover reductions in msh4-R676W and msh4Δ were significant across chromosomes regardless of size, unlike previous observations made at specific loci.The msh4-R676W hypomorph showed reduced crossover interference.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 hypomorph.
Affiliation: School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Trivandrum 695016, India.Show MeSH
Mentions: We analyzed crossover and noncrossover events in the msh4–R676W hypomorph. The average number of crossovers was reduced to 64.2 / meiosis while the noncrossovers were 55.2 / meiosis (Table 1 and Figure 1). The reduction in crossovers compared to wild type is statistically significant for the msh4–R676W hypomorph (t-test, P = 4.18 × 10−9). Noncrossovers were not statistically different from wild type (t-test, P = 0.77). These results suggest there is a genome-wide reduction in crossing over in the msh4–R676W hypomorph while noncrossovers are similar to wild type. Representative crossover and noncrossover distributions along chromosome IV for wild type and msh4–R676W hypomorph are shown in Figure 2, A and B. For the msh4Δ mutant, average crossovers were reduced to 49.5 / meiosis (t-test, P = 2.93 × 10−10), while noncrossovers (69.7 / meiosis, 56 median) were similar to wild type (t-test, P = 0.12). The data for msh4Δ are consistent with previous analysis of msh4Δ tetrads in the S288c x YJM789 hybrid where crossovers showed a twofold reduction while noncrossovers were unchanged (Chen et al. 2008; Mancera et al. 2008; Oke et al. 2014). Collectively these results suggest that in the msh4–R676W hypomorph and msh4Δ mutant, crossovers are reduced on a genome-wide scale while noncrossovers are maintained (Figure 1). These results suggest that most of the DSBs that cannot be repaired as crossovers in msh4 mutants are repaired using inter-sister recombination. It is also possible that the restoration/conversion ratio is perturbed in the msh4 mutants in favor of restoration of the SNP markers so that more noncrossovers are not detected.
Affiliation: School of Biology, Indian Institute of Science Education and Research, Thiruvananthapuram, Trivandrum 695016, India.