MM-0001_Study_0001
The baker’s yeast diploid genome is remarkably stable in vegetative growth and meiosis
Accurate estimates of mutation rates in vegetative and meiotic cell cycles provide critical information to analyze genome evolution and organism fitness.  We used whole-genome DNA sequencing, pulse-field gel electrophoresis, and comparative genome hybridization to determine mutation rates in diploid vegetative and meiotic mutation accumulation lines of Saccharomyces cerevisiae.  Similar base substitution rates (per cell division) were observed in the vegetative (2.9 x 10-10) and meiotic (3.9 x 10-10) lines.  Simulations of our bottleneck scheme indicated that the meiotic mutation rate could be 25 to 55-fold higher than the vegetative rate without showing a statistically significant difference between the two.  Mutations detected in vegetative lines were all heterozygous while those in meiotic lines were homozygous.  A quantitative analysis of intra-tetrad mating events in the meiotic lines showed that inter-spore mating is primarily responsible for rapidly fixing mutations in the meiotic lines to homozygosity as well as for removing mutations.  We did not observe insertion/deletion (in-del, 1-2 nt) mutations in any of the sequenced lines and only one structural variant in an internal chromosomal location was found.  However, a large number of structural variations in subtelomeric sequences were seen in both vegetative and meiotic lines that did not affect viability, as measured by tetrad analysis.  In contrast to previous work performed in haploid yeast, our results indicate that the diploid yeast genome is remarkably stable during the vegetative and meiotic cell cycles and support the hypothesis that peripheral regions of chromosomes are more dynamic than gene-rich central sections where structural rearrangements could be deleterious.  This work also provides an improved estimate for the mutational load carried by diploid organisms, and is consistent with a recent bioinformatics study suggesting that recombination during meiosis in the wild is unlikely to create a mutational load for organisms.