Yeast Spontaneous Mutation Rate and Spectrum Vary with Environment

Mutation is the ultimate genetic source of evolution and biodiversity, but to what extent the environment impacts mutation rate and spectrum is poorly understood. Past studies discovered mutagenesis induced by antibiotic treatment or starvation, but its relevance and importance to long-term evolution is unclear because these severe stressors typically halt cell growth and/or cause substantial cell deaths. Here, we quantify the mutation rate and spectrum in Saccharomyces cerevisiae by whole-genome sequencing following mutation accumulation in each of seven environments with relatively rapid cell growths and minimal cell deaths. We find the point mutation rate per generation to differ by 3.6-fold among the seven environments, generally increasing in environments with slower cell growths. This trend renders the mutation rate per year more constant than that per generation across environments, which has implications for neutral evolution and the molecular clock. Additionally, we find substantial among-environment variations in mutation spectrum, such as the transition to transversion ratio and AT mutational bias. Other main mutation types, including small insertion or deletion, segmental duplication or deletion, and chromosome gain or loss also tend to occur more frequently in environments where yeast grows more slowly. In contrast to these findings from the nuclear genome, the yeast mitochondrial mutation rate rises with the growth rate, consistent with the metabolic rate hypothesis. Together, these observations indicate that environmental changes, which are ubiquitous in nature, influence not only natural selection, but also the amount and type of mutations available to selection, and suggest that ignoring the latter impact, as is currently practiced, may mislead evolutionary inferences.