Abstract
There is significant variation in the rate and spectrum of spontaneous mutations among taxa. How this variation is shaped by natural selection remains a subject of debate. The drift-barrier hypothesis proposes that selection generally favors lower mutation rates due to the risk of deleterious mutations but acts less effectively against weak mutator alleles in smaller populations, allowing the mutation rate to increase due to genetic drift. Given this model, we propose that mutation rates may also be elevated in cell types that appear rarely in a population, where DNA replication and repair processes are subject to selection less often. We can begin to test this prediction in yeast species, some of which can be grown in either a haploid or diploid cell state. Existing data on the budding yeast Saccharomyces cerevisiae support this prediction, with a higher mutation rate observed in haploids, which is the rare cell type in natural populations. However, this pattern could also appear if haploidy is inherently mutagenic, regardless of the dominant cell type. To test these alternatives, we conducted a mutation accumulation experiment with haploid and diploid cells of the fission yeast Schizosaccharomyces pombe, in which diploidy is the rare cell type. In this species, we found a higher mutation rate in diploids, consistent with our prediction. In both species, the spectrum of mutations is also influenced by ploidy state. Our findings suggest that limits to selection on mutation may be evident as variation within species.