EvoLunch Seminar: Linda Odenthal-Hesse (Max Planck Institute for Evolutionary Biology)

Meiosis is essential for gamete formation, and its failure represents a major cause of infertility and pregnancy loss. In the house mouse (Mus musculus), recombination is highly regulated and directed by the rapidly evolving histone methyltransferase PRDM9, which determines the genomic locations of meiotic double-strand breaks. Owing to its recent evolutionary divergence and exceptional genetic diversity, Mus musculus provides a uniquely powerful system to dissect the mechanisms and evolution of meiotic recombination. Here, we leverage a global collection of over 1,000 wild-derived and laboratory mouse samples, assembled over decades by the international mouse genetics community, to systematically characterise natural variation in Prdm9. We characterised more than 270 alleles in Mus musculus, including over forty previously undescribed variants, and developed a novel phylogenetic framework to resolve the evolution of its rapidly changing coding minisatellite. To enable other researchers to analyse Prdm9 variation in their own samples and integrate these data into a growing community resource, we established a protocol and a scalable bioinformatic toolkit. Together, these analyses reveal pronounced lineage-specific dynamics across subspecies and complex genomic backgrounds, including t-haplotypes, highlighting PRDM9 as one of the most rapidly evolving regulators of genome function in mammals. Building on a decade-long collaboration with the Jiří Forejt laboratory on the microRNA-mediated pachytene checkpoint, we extend this discovery and show that variation in the dosage of specific regulatory small RNAs modulates recombination dynamics and hybrid male fertility. Together, these findings establish Mus musculus as a central model for uncovering the multi-layered genetic and evolutionary architecture of meiotic control.