Epigenetic inheritance in adaptive evolution.

Since the Modern Synthesis, our ideas of evolution have mostly centered on the information encoded in the DNA molecule and their mechanisms of heredity. Increasing evidence, however, suggests that epigenetic mechanisms have the potential to perpetuate gene activity states in the context of the same DNA sequence. Here, we discuss recent compelling evidence showing that epigenetic signals triggered by environmental stress can persist over very long timeframes, contributing to phenotypic changes in relevant traits upon which selection could act. We argue that epigenetic inheritance plays an important role in fast phenotypic adaptation to fluctuating environments, ensuring the survival of the organisms of a population under environmental stress in the short term while maintaining a "bet-hedging" strategy of reverting to the original state if the environment returns to standard conditions. These examples call for a reevaluation of the role of nongenetic information in adaptive evolution, raising questions about its broader relevance in nature.

Molecular mechanisms of transgenerational epigenetic inheritance.

Increasing evidence indicates that non-DNA sequence-based epigenetic information can be inherited across several generations in organisms ranging from yeast to plants to humans. This raises the possibility of heritable 'epimutations' contributing to heritable phenotypic variation and thus to evolution. Recent work has shed light on both the signals that underpin these epimutations, including DNA methylation, histone modifications and non-coding RNAs, and the mechanisms by which they are transmitted across generations at the molecular level. These mechanisms can vary greatly among species and have a more limited effect in mammals than in plants and other animal species. Nevertheless, common principles are emerging, with transmission occurring either via direct replicative mechanisms or indirect reconstruction of the signal in subsequent generations. As these processes become clearer we continue to improve our understanding of the distinctive features and relative contribution of DNA sequence and epigenetic variation to heritable differences in phenotype.

Large domains of heterochromatin direct the formation of short mitotic chromosome loops.

During mitosis chromosomes reorganise into highly compact, rod-shaped forms, thought to consist of consecutive chromatin loops around a central protein scaffold. Condensin complexes are involved in chromatin compaction, but the contribution of other chromatin proteins, DNA sequence and histone modifications is less understood. A large region of fission yeast DNA inserted into a mouse chromosome was previously observed to adopt a mitotic organisation distinct from that of surrounding mouse DNA. Here, we show that a similar distinct structure is common to a large subset of insertion events in both mouse and human cells and is coincident with the presence of high levels of heterochromatic H3 lysine nine trimethylation (H3K9me3). Hi-C and microscopy indicate that the heterochromatinised fission yeast DNA is organised into smaller chromatin loops than flanking euchromatic mouse chromatin. We conclude that heterochromatin alters chromatin loop size, thus contributing to the distinct appearance of heterochromatin on mitotic chromosomes.