Fluctuations in chromatin state at regulatory loci occur spontaneously under relaxed selection and are associated with epigenetically inherited variation in C. elegans gene expression

Author summaryEvolution is known to occur because of changes in DNA sequence which are inherited between generations. Recently, though, it has been discovered that information beyond the DNA sequence can be transmitted between generations. This information, known as epigenetic, can control how the DNA sequence is used. Epigenetic information that is transmitted between generations could drive evolutionary processes in populations, but this is yet to be tested. We used a simple nematode worm to investigate the contribution of different types of epigenetic information to evolution. We evolved populations of worms in the laboratory and investigated epigenetic differences that emerged in different lineages. Most epigenetic differences were very short-lived, so unlikely to be able to contribute to long-term evolutionary processes. However, we identified some changes that lasted much longer. Intriguingly, genes that control the worms' responses to external threats such as bacterial infections or noxious chemicals were most likely to undergo long-term epigenetic changes, despite the fact that the environment of the worms was stable and did not contain these stresses. We think that epigenetic processes might be able to create a fast-acting form of variation that could help in situations where organisms need to adapt to dangerous environments. Some epigenetic information can be transmitted between generations without changes in the underlying DNA sequence. Changes in epigenetic regulators, termed epimutations, can occur spontaneously and be propagated in populations in a manner reminiscent of DNA mutations. Small RNA-based epimutations occur in C. elegans and persist for around 3-5 generations on average. Here, we explored whether chromatin states also undergo spontaneous change and whether this could be a potential alternative mechanism for transgenerational inheritance of gene expression changes. We compared the chromatin and gene expression profiles at matched time points from three independent lineages of C. elegans propagated at minimal population size. Spontaneous changes in chromatin occurred in around 1% of regulatory regions each generation. Some were heritable epimutations and were significantly enriched for heritable changes in expression of nearby protein-coding genes. Most chromatin-based epimutations were short-lived but a subset had longer duration. Genes subject to long-lived epimutations were enriched for multiple components of xenobiotic response pathways. This points to a possible role for epimutations in adaptation to environmental stressors.

Automated summary

Recently, it has been discovered that there is information beyond the DNA sequence, known as epigenetic information, that can be transmitted between generations and control how the DNA sequence is used. We investigated the contribution of different types of epigenetic information to evolution using nematode worms. Most epigenetic differences were short-lived, but we identified some changes that lasted longer, particularly in genes related to the worms' responses to external threats.