Genome-wide survey of post-meiotic segregation during yeast recombination

Abstract

Background: When mismatches in heteroduplex DNA formed during meiotic recombination are left unrepaired, post-meiotic segregation of the two mismatched alleles occurs during the ensuing round of mitosis. This gives rise to somatic mosaicism in multicellular organisms and leads to unexpected allelic combinations among progeny. Despite its implications for inheritance, post-meiotic segregation has been studied at only a few loci.

Results: By genotyping tens of thousands of genetic markers in yeast segregants and their clonal progeny, we analyzed post-meiotic segregation at a genome-wide scale. We show that post-meiotic segregation occurs in close to 10% of recombination events. Although the overall number of markers affected in a single meiosis is small, the rate of post-meiotic segregation is more than five orders of magnitude larger than the base substitution mutation rate. Post-meiotic segregation took place with equal relative frequency in crossovers and non-crossovers, and usually at the edges of gene conversion tracts. Furthermore, post-meiotic segregation tended to occur in markers that are isolated from other heterozygosities and preferentially at polymorphism types that are relatively uncommon in the yeast species.

Conclusions: Overall, our survey reveals the genome-wide characteristics of post-meiotic segregation. The results show that post-meiotic segregation is widespread in meiotic recombination and could be a significant determinant of allelic inheritance and allele frequencies at the population level.

Figure 1

Genome-wide post-meiotic segregation mapping. Schematic description of the approach to map post-meiotic segregation (PMS) genome-wide. The four pairs of mother-daughter cells resulting from the first mitosis of each spore were genotyped using a tiling microarray.

Figure 2

Examples of post-meiotic segregation. (a,b) Close-ups of a NCO in chromosome VI (a) and a CO in chromosome XVI (b) containing markers where PMS occurred. Red/blue vertical segments represent markers with the S288c/YJM789 genotype along the chromosomes of the two mother and daughter cells resulting from the first mitosis of each spore (A, B, C and D). The horizontal black line indicates the inferred NCO, and the diagonal, the CO. Green vertical segments immediately on top of the coordinate axis denote markers where PMS occurred and orange segments denote markers with non-Mendelian segregation.

Figure 3

Post-meiotic segregation markers are relatively isolated from other polymorphisms. Histograms showing the marker density in 100-bp windows centered on PMS markers (upper panel), centered on markers located at the end of conversion tracts (middle panel), and centered on overall markers in recombination intervals (lower panel). A range of window sizes produced qualitatively similar results. The median distance to the nearest polymorphism for markers at the end of conversion tracts was 58 bp larger than for all markers in recombination events (Wilcoxon test, P < 0.0001) and the median distance to the nearest polymorphism for PMS markers was 49 bp larger than for all end-of-interval markers (Wilcoxon test, P = 0.002).

Figure 4

Post-meiotic segregation occurs preferentially at specific polymorphism types. (a) Relative frequencies of the possible mismatches given the SNPs found in PMS events and in recombination events (Rec. SNPs). (b) Inverse relationship between the frequency of the different SNP types in the S. cerevisiae species and the efficiency with which the mismatches generated by the SNPs are repaired (PMS relative rate = PMS frequency/Recombination SNP frequency). In the figure the frequencies of SNPs between S288c and YJM789 are shown. The result is qualitatively the same when calculating SNP frequencies with other strains [37].