Competing crossover pathways act during meiosis in Saccharomyces cerevisiae

Abstract

In Saccharomyces cerevisiae the MSH4-MSH5, MLH1-MLH3, and MUS81-MMS4 complexes act to promote crossing over during meiosis. MSH4-MSH5, but not MUS81-MMS4, promotes crossovers that display interference. A role for MLH1-MLH3 in crossover control is less clear partly because mlh1Delta mutants retain crossover interference yet display a decrease in crossing over that is only slightly less severe than that seen in msh4Delta and msh5Delta mutants. We analyzed the effects of msh5Delta, mlh1Delta, and mms4Delta single, double, and triple mutants on meiotic crossing over at four consecutive genetic intervals on chromosome XV using newly developed computer software. mlh1Delta mms4Delta double mutants displayed the largest decrease in crossing over (13- to 15-fold) of all mutant combinations, yet these strains displayed relatively high spore viability (42%). In contrast, msh5Delta mms4Delta and msh5Delta mms4Delta mlh1Delta mutants displayed smaller decreases in crossing over (4- to 6-fold); however, spore viability (18-19%) was lower in these strains than in mlh1Delta mms4Delta strains. These data suggest that meiotic crossing over can occur in yeast through three distinct crossover pathways. In one pathway, MUS81-MMS4 promotes interference-independent crossing over; in a second pathway, both MSH4-MSH5 and MLH1-MLH3 promote interference-dependent crossovers. A third pathway, which appears to be repressed by MSH4-MSH5, yields deleterious crossovers.

Figure 1.—

Distribution of genetic markers on chromosome XV. The solid circle indicates the centromere. The distances between markers are not drawn to scale. The actual physical and genetic distances in the wild-type diploid are given numerically for each interval and for the entire region between CENXV and HIS3.

Figure 2.—

Plots showing the distribution of viable spores in tetrads of each genotype. In all plots, the horizontal axis corresponds to the classes of tetrads with 4, 3, 2, 1, and 0 viable spores, and the vertical axis corresponds to the frequency of each class given in a percentage. The total number of tetrads dissected (n) and the overall spore viability (SV) are shown for each genotype.

Figure 3.—

Summary of the relationship between spore viability and meiotic crossing over. (A) Percentage of spore viability. (B) Cumulative genetic distances between URA3 and HIS3 measured from tetrads (T) and single spores (S). Each bar is divided into four sectors corresponding to the four genetic intervals in the region of chromosome XV analyzed. The size of the sectors is proportional to the contribution of each interval to the total URA3-HIS3 genetic distance.

Figure 4.—

Proposed organization of the meiotic crossover control pathway. The thickness of each line corresponds roughly to the relative contribution of each branch to the overall generation of crossovers. See text for details.