The Spontaneous Mutation Rate in the Fission Yeast Schizosaccharomyces pombe

Abstract

The rate at which new mutations arise in the genome is a key factor in the evolution and adaptation of species. Here we describe the rate and spectrum of spontaneous mutations for the fission yeast Schizosaccharomyces pombe, a key model organism with many similarities to higher eukaryotes. We undertook an 1700-generation mutation accumulation (MA) experiment with a haploid S. pombe, generating 422 single-base substitutions and 119 insertion-deletion mutations (indels) across the 96 replicates. This equates to a base-substitution mutation rate of 2.00 3 10 210 mutations per site per generation, similar to that reported for the distantly related budding yeast Saccharomyces cerevisiae. However, these two yeast species differ dramatically in their spectrum of base substitutions, the types of indels (S. pombe is more prone to insertions), and the pattern of selection required to counteract a strong AT-biased mutation rate. Overall, our results indicate that GC-biased gene conversion does not play a major role in shaping the nucleotide composition of the S. pombe genome and suggest that the mechanisms of DNA maintenance may have diverged significantly between fission and budding yeasts. Unexpectedly, CpG sites appear to be excessively liable to mutation in both species despite the likely absence of DNA methylation.KEYWORDS mutation accumulation; effective population size; biased gene conversion; fission yeast M UTATION is the ultimate source of all genetic differences within and among species. Mutation may alter the sequence of the genome via single-base substitutions; change the length of the genome by means of insertions, deletions, and duplications; or alter genome architecture via changes in chromosomal ploidy. The rate at which each of these events occurs in nature is largely obscured in a comparison of individuals or species owing to the action of natural selection and drift. An unbiased estimate of the rate and spectrum of spontaneous mutations can be obtained by passing replicate individuals through thousands of generations of mutation accumulation (MA). Under this protocol, which imposes a very small effective population size during passage, selection will have little influence on the fate of new mutations.The fission yeast Schizosaccharomyces pombe is a member of the largest and most diverse fungal phylum, Ascomycota, and is a key model system in cell biology. In the wild, S. pombe occurs in small, incompletely isolated populations with only weak population structure resulting from recent global dispersal (Brown et al. 2011;Jeffares et al. 2015). Beyond this, little is known of its natural ecology. It is, however, often recovered from natural fermentations and was isolated originally from East African millet beer.Notwithstanding the uncertainty regarding its ecology, the life cycle of S. pombe in the wild is likely to be predominantly haploid. In a collection of 81 natural isolates, all but one were haploid, with the sole diploid most likely resulting from biparental inbreeding (Brown et al. 2011). ...

Preferential Protection of Genetic Fidelity within Open Chromatin by the Mismatch Repair Machinery

“…4B). This differs from what was observed in budding yeast S. cerevisiae (36), but it is consistent with a recent fission yeast S. pombe study (37). This is an interesting observation because it suggests that although both insertions and deletions create looped-out structures in double-stranded DNA, they are likely to be differentially sensed by the mismatch machinery, because insertions Five independent mutation accumulation lines were created for each strain to undergo 100 single-cell bottleneck passages (P 0 to P 100 ).…”

Antibiotic treatment enhances the genome-wide mutation rate of target cells

“…Genetic drift in single-cell bottlenecked lines of E. coli is strong enough to prevent the operation of selection on all but mutations with very large effects (31), and numerous prior studies of this sort have validated the effectively nonselective nature of MA experiments (27,28,33,38,39). However, to directly test whether selection might have biased the mutation rate/spectrum (e.g., by enriching for mutations conferring norfloxacin resistance), we examined the synonymous and nonsynonymous status of each coding-region BPS (Dataset S1, Table S2).…”

“…MA experiments using bacteria are performed by repeatedly passing large numbers of initially identical lines through single-cell bottlenecks, a procedure that prevents natural selection from promoting or eradicating nearly all mutations, except the small subset with extremely large effects (31). This MA/WGS procedure provides an essentially unbiased, genomewide view of the rate and full molecular spectrum of mutations, and has yielded accurate estimates of these features in a wide variety of prokaryotic and eukaryotic microbes (27,28,(32)(33)(34).…”

Frequency and type of inheritable mutations induced by γ rays in rice as revealed by whole genome sequencing

“…−10 (Zhu et al, 2014) to 2.00×10 −10 mutations per base per generation (Farlow et al, 2015) in yeast. The differences of spontaneous mutation rates between rice and Arabidopsis should not be greater than those between Arabidopsis and Chlamydomonas reinhardtii or between Arabidopsis and yeast, because phylogenetic Arabidopsis is more conserved with rice than with Chlamydomonas reinhardtii or yeast.…”