Professor of Mathematical Genomics
Department of Statistics
Wellcome Trust Centre for Human Genetics
University of Oxford
Host: Molly Przeworski
Title: Good things come in pairs: genetic diversity and fertility, synapsis and recombination
Abstract: During mammalian meiosis homologous chromosomes must pair (synapse) and exchange DNA. This is essential for fertility, enables balanced segregation, and generates genetic diversity. Work by our lab and others has shown that in many vertebrates, the double-strand breaks (DSBs) that initiate exchange occur at sites where the protein PRDM9 binds and deposits both H3K4me3 and H3K36me3. We will discuss work showing that PRDM9 also plays a role in homologous chromosome pairing, and explaining how genetic diversity disrupts this process in some mouse hybrids, leading to sterility and, potentially, speciation. Moreover, we will describe new work showing that a previously uncharacterised protein, ZCWPW1, which is essential for proper male synapsis, recognises and binds to PRDM9-bound sites and CpG sites throughout the genome, and has co-evolved with PRDM9 across vertebrates. Taken together, our results strongly support a functional interaction between PRDM9 and ZCWPW1, downstream of DSB formation.