Epigenetic modifications affect the rate of spontaneous mutations in a pathogenic fungus

While a correlation between epigenetic modifications and mutation rates has been observed, experimental evidence of causality is limited. Here the authors measure the mutation rate in fungal mutants lacking histone modifications and confirm experimentally a causal effect of epigenetic modifications on mutation rates. Mutations are the source of genetic variation and the substrate for evolution. Genome-wide mutation rates appear to be affected by selection and are probably adaptive. Mutation rates are also known to vary along genomes, possibly in response to epigenetic modifications, but causality is only assumed. In this study we determine the direct impact of epigenetic modifications and temperature stress on mitotic mutation rates in a fungal pathogen using a mutation accumulation approach. Deletion mutants lacking epigenetic modifications confirm that histone mark H3K27me3 increases whereas H3K9me3 decreases the mutation rate. Furthermore, cytosine methylation in transposable elements (TE) increases the mutation rate 15-fold resulting in significantly less TE mobilization. Also accessory chromosomes have significantly higher mutation rates. Finally, we find that temperature stress substantially elevates the mutation rate. Taken together, we find that epigenetic modifications and environmental conditions modify the rate and the location of spontaneous mutations in the genome and alter its evolutionary trajectory.

Automated summary

In this study, the authors demonstrated a causal effect of epigenetic modifications on mutation rates in fungal pathogens, as well as the impact of temperature stress and cytosine methylation on the rate and location of spontaneous mutations in the genome. Additionally, they found that histone modifications and transposable elements can significantly affect mutation rates.