Epigenetic gene silencing alters the mechanisms and rate of evolutionary adaptation

Abstract

Epigenetic, non-DNA sequence-based inheritance can potentially contribute to adaptation but, due to its transient nature and the difficulty involved in uncoupling it from genetic variation, it is unclear whether it has any effect on long-term evolution. However, short-term epigenetic inheritance may interact with genetic change by modifying the rate and type of adaptive mutations. Here, we test this notion in an experimental evolution set-up in yeast. We tune low, intermediate and high levels of heritable silencing of a URA3 reporter under selection by insertion at different positions within silent subtelomeric chromatin in otherwise isogenic Saccharomyces cerevisiae. Heritable silencing does not impact mutation rate but drives population size expansion and rapid epigenetic adaptation. This eventually leads to genetic assimilation of the silent phenotype by mutations that reduce or abolish URA3 expression. Moreover, at intermediate or low levels of heritable silencing we find that populations evolve more rapidly by accumulation of adaptive mutations, in part through acquisition of novel alleles that enhance gene silencing, aiding accelerated adaptation. We provide an experimental proof of concept that defines the impact and mechanisms of how short-term epigenetic inheritance can shape adaptive evolution.

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Data availability

Whole-genome sequence data for all strains listed in Supplementary Fig. 6 are available at the National Center for Biotechnology Information Sequence Read Archive, accession no. SRP129019.

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Acknowledgements

We thank R. Kolodner (University of California, San Diego) and E. Louis (University of Leicester) for strains, and I. Gordo, P. Beldade, C. Bank, M. Ferreira (all Instituto Gulbenkian de Ciência), L.-M. Chevin (Centre National de la Recherche Scientifique, Montpellier) and T. Flatt (University of Fribourg) for helpful comments and suggestions. We acknowledge the Instituto Gulbenkian de Ciência Gene Expression Unit for genome sequencing support. Salary support to D.S. was provided by the Fundação para a Ciência e a Tecnologia fellowship (no. SFRH/BD/52170/2013), and Investigador FCT positions to L.P. and L.E.T.J. This work was supported by the Instituto Gulbenkian de Ciência.

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D.S., L.P. and L.J. conceived the study and designed the experiments. D.S. constructed the strains and performed the experiments. D.S., L.P. and L.J. critically analysed the data. D.S. and L.J. created the figures. D.S., L.P. and L.J. wrote the manuscript. L.P. and L.J. provided resources, funding and supervision.

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Correspondence to Lília Perfeito or Lars E. T. Jansen.

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Stajic, D., Perfeito, L. & Jansen, L.E.T. Epigenetic gene silencing alters the mechanisms and rate of evolutionary adaptation. Nat Ecol Evol 3, 491–498 (2019). https://doi.org/10.1038/s41559-018-0781-2

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