S. cerevisiae ploidy by REV1 mutation accumulation WGS

The impact of selection versus genetic drift on mutation patterns is unclear. We previously found that, in the diplontic yeast S. cerevisiae, haploid cells have a >2-fold higher mutation rate than diploids, suggesting that haploid-specific mutator alleles may be present due to the limited opportunity for selection to act on this rare cell type. Because this ploidy-specific effect on mutation rate was driven by an abundance of single-nucleotide mutations (SNMs) in late-replicating regions of the haploid genome, we predicted that these haploid-specific mutator alleles are involved in the recruitment of error-prone translesion synthesis (TLS) polymerases in late-replicating regions. Additional research has demonstrated that removing REV1, a gene responsible for initiating TLS, causes a reduction in haploid mutation rate. To assess whether the preferential use of this error-prone repair pathway by haploids explains the difference in genome-wide mutation patterns between cell types, we deleted REV1 in both diploid and haploid S. cerevisiae and estimated their mutation rates using a mutation accumulation experiment. Consistent with our previous study, we found a 50% higher per-nucleotide SNM rate in REV1+ haploids than REV1+ diploids. We also found that deleting the REV1 gene caused this difference to vanish, with SNM rates in both haploid and diploid rev1 knockout lines decreasing significantly. Taken together, these results suggest that the mutagenic effect of translesion synthesis is haploid-specific, and that the difference in genome-wide mutation rates between ploidies is driven by limited opportunity for selection to act on haploid-specific mutator alleles involved in TLS.