Evolutionary Arms Races Shaping the Germline Epigenome

Introduction

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.

Genetic Conflicts

These include conflicts between:

• Transposons and host genomes
• Chromosomes during meiosis
• Maternal and paternal epigenomes

Such genetic conflicts are predicted to drive evolutionary arms races leading to rapid genetic and epigenetic innovations.

Research Focus

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. Short Histone H2A Variants
   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 by 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. Functional Diversification in Chromatin Remodeling Enzymes
   Using in-depth phylogenomics and selection analyses, we uncovered novel signatures of functional diversification in rodent and primate chromatin remodeling enzymes. We propose to systematically identify these innovations across mammalian germline chromatin pathways.

3. Comparative Epigenome Profiling
   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.

Conclusion

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.