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Evolutionary Arms Races Shaping the Germline Epigenome

Project description

Epigenetics meets evolutionary biology

Germline inheritance ensures the transmission of genetic and epigenetic information across generations, playing a crucial role in reproduction and species’ continuity. Chromatin pathways such as modification and remodelling play a central role in this transmission as well as in evolutionary battles: for example, between jumping genes and the host genome. The scope of the ERC-funded EvoEpi project is to understand how these chromatin pathways evolve and how their rapid diversification impacts reproduction and inheritance. Considering that disruptions in these inheritance mechanisms can lead to infertility and developmental disorders, project results will shed light on reproductive health and development. Moreover, outcomes are expected to challenge the idea that epigenetic marks remain mostly unchanged over time.

Objective

Germline chromatin pathways are key to the stable inheritance of genetic and epigenetic information. They also participate in intense evolutionary battles between genetic entities with opposite incentives during reproduction. These include conflicts between transposons and host genomes, between chromosomes during meiosis, and between maternal and paternal epigenomes. Such genetic conflicts are predicted to drive evolutionary arms races leading to rapid genetic and epigenetic innovations. Contrary to current dogmas focusing on conserved features, my research program explicitly tackles the functional consequences of epigenome rapid evolution during mammalian reproduction and disease, including in humans. With the support of the ERC, we want to harvest this unique perspective on the germline epigenome to explore novel inheritance paradigms:
(1) Using mouse models, we discovered that rapidly evolving short histone H2A variants function in a novel imprinting-like conflict during reproduction. We will identify the mechanisms underlying these functions combining epigenome profiling with evolution-guided hypothesis testing in vivo. We then seek to explore their contributions to reproductive barriers using functional genetics across mouse sub-species.
(2) Using in-depth phylogenomics and selection analyses, we uncovered novel signatures of functional diversification in rodent and primate chromatin remodelling enzymes. We propose to systematically identify these innovations across mammalian germline chromatin pathways.
(3) To study the chromatin consequences of these innovations, we designed a surrogate system in human and mouse cells for comparative epigenome profiling. We will use this approach to uncover the breadth of epigenome regulatory mechanisms shaped by potential genetic conflicts in vivo.

In sum, this proposal interfaces our unique expertise in epigenomics and evolution to transform our current understanding of epigenome regulation and its impact on reproduction.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-COG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 996 223,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 996 223,00

Beneficiaries (1)

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