Epimutations in Caenorhabditis elegans mutation accumulation lines

Epigenetic regulation involves changes in gene expression independent of DNA sequence variation that are inherited through cell division. In addition to a fundamental role in cell differentiation, some epigenetic changes can also be transmitted transgenerationally through meiosis. Epigenetic alterations (“epimutations”) could thus contribute to heritable variation within populations and be acted on by evolutionary processes such as natural selection and drift. However, this suggestion is controversial, partly because unlike classical mutations involving DNA sequence changes, key parameters such as the rate at which epimutations arise and their stability are unclear. Here, we study epimutations genome-wide for the first time in a metazoan organism. We use experimental evolution to characterise the rate, spectrum and stability of epimutations driven by small silencing RNAs in the model nematode C. elegans. We show that epimutations arise spontaneously at a rate ~25 times greater than DNA sequence changes but have a short half-life of 2-3 generations. Our results suggest that epimutations may contribute to evolutionary processes over a very short timescale but are unlikely to bring about long-term divergence without further DNA sequence changes.