On the origin of PRDM9-guided recombination hotspots

francisco ubeda

Department of Biological Sciences, Royal Holloway University of London, UK

www.intragenomicconflict.co.uk, f.ubeda@rhul.ac.uk

Link to onsite registration: https://duo.dr13.cnrs.fr/public/evenement/index

Link to seminar:  https://umontpellier-fr.zoom.us/webinar/register/WN_g61__faYRl66KAckYZro9A

The re-shuffling of genes during meiosis (recombination) plays a central role in genetics. Recombination is not uniformly distributed in the genome but clusters in recombination hotspots. In vertebrates, two types of hotspots have been observed: those guided by gene PRDM9 (PRDM9-guided recombination hotspots) and those that do not (non-PRDM9-guided recombination hotspots). PRDM9-guided recombination hotspots are found in most mammals (including humans) and characterised for initiating recombination in specific DNA-sequence motifs encoded by gene PRDM9. Because motifs enabling recombination are converted into motifs preventing recombination, these hotspots are short-lived, and often referred to as self-destructive recombination hotspots. Non-PRDM9-guided recombination hotspots are found in most birds and characterised for initiating recombination not in specific DNA-sequence motifs but in gene promoters. Because they act independently of any motif, these hotspots are long-lived, and can be referred to as self-preserving recombination hotspots. These two types of hotspots are considered alternative ways of achieving the same goal: gene re-shuffling and proper chromosomal segregation. While is unclear which type of hotspot evolved first, phylogenetic distribution shows transitions from non-PRDM9-guided to PRDM9-guided and vice-versa. What drives the evolution of a type of recombination hotspot in the presence of the other type remains a mystery. Here we formulate a population genetics model to explore the evolution of self-preserving and self-destructive recombination hotspots. We show that in the absence of any difference between hotspots other than their affinity for DNA-motifs, all transitions should be from PRDM9-guided ones to non-PRDM9-guided ones and eventually PRDM9-guided recombination hotspots should become extinct. However, PRDM9-guided recombination hotspots are abundant. Our work unveils a contradiction that requires an explanation. We conclude that PRDM9-guided recombination hotspots require an evolutionary advantage over non-PRDM9-guided to overcome their intrinsic, mechanistic, disadvantage.

Watch previous seminars on our YouTube channel: https://www.youtube.com/channel/UCrX4IsZ8WIFcDa0ZmC7rcQg