Loss of Heterozygosity and Base Mutation Rates Vary Among<i>Saccharomyces cerevisiae</i>Hybrid Strains

Abstract

A growing body of evidence suggests that mutation rates exhibit intra-species specific variation. We estimated genome-wide loss of heterozygosity (LOH), gross chromosomal changes, and single nucleotide mutation rates to determine intra-species specific differences in hybrid and homozygous strains of <i>Saccharomyces cerevisiae</i> The mutation accumulation lines of the <i>S. cerevisiae</i> hybrid backgrounds - S288c/YJM789 (S/Y) and S288c/RM11-1a (S/R) were analyzed along with the homozygous diploids RM11, S288c, and YJM145. LOH was extensive in both S/Y and S/R hybrid backgrounds. The S/Y background also showed longer LOH tracts, gross chromosomal changes, and aneuploidy. Short copy number aberrations were observed in the S/R background. LOH data from the S/Y and S/R hybrids were used to construct a LOH map for S288c to identify hotspots. Further, we observe up to a sixfold difference in single nucleotide mutation rates among the <i>S. cerevisiae</i> S/Y and S/R genetic backgrounds. Our results demonstrate LOH is common during mitotic divisions in <i>S. cerevisiae</i> hybrids and also highlight genome-wide differences in LOH patterns and rates of single nucleotide mutations between commonly used <i>S. cerevisiae</i> hybrid genetic backgrounds.