Recent insights into the evolution of mutation rates in yeast

Abstract

Mutation is the origin of all genetic variation, good and bad. The mutation process can evolve in response to mutations, positive or negative selection, and genetic drift, but how these forces contribute to mutation-rate variation is an unsolved problem at the heart of genetics research. Mutations can be challenging to measure, but genome sequencing and other tools have allowed for the collection of larger and more detailed datasets, particularly in the yeast-model system. We review key hypotheses for the evolution of mutation rates and describe recent advances in understanding variation in mutational properties within and among yeast species. The multidimensional spectrum of mutations is increasingly recognized as holding valuable clues about how this important process evolves.

Figure 1.

Mutations in yeast occur on multiple scales, from single-nucleotide changes to whole genome duplication. There is evidence for variability in mutation patterns at every genomic scale, as well as among strains, species and environments. Example references are indicated for each type of variation.

Figure 2.. Mutation rates in yeast genes.

Bars show observed frequencies of mutations from three MA studies of S. cerevisiae (A) in genes, as a fraction of the whole genome, and (B) in essential genes relative to all genes. Dashed red lines represent the expected frequency if mutations occur in an unbiased fashion with respect to genes (A) or essential genes (B). These expected values account for gene length but do not incorporate other sources of mutation rate variation across the genome or variation in detection power. Values shown on bars indicate sample sizes, i.e., the total number of mutations observed in each category. Data from Ref. are aggregated over ploidy levels and genotypes. Data from Ref. are aggregated over environments; there is no evidence for a deviation from the null expectation in any individual environment. Indel mutations are observed in genes less often than expected, but are not observed in essential genes less often than expected; the deficit of genic indels may therefore reflect differences in sequence complexity between genic and intergenic regions. Overall, there is little evidence that mutations in this species occur less often in selectively-constrained regions.