PRDM9 drives the location and rapid evolution of recombination hotspots in salmonids

Abstract

In many eukaryotes, meiotic recombination occurs preferentially at discrete sites, called recombination hotspots. In various lineages, recombination hotspots are located in regions with promoter-like features and are evolutionarily stable. Conversely, in some mammals, hotspots are driven by PRDM9 that targets recombination away from promoters. Paradoxically, PRDM9 induces the self-destruction of its targets and this triggers an ultra-fast evolution of mammalian hotspots. PRDM9 is ancestral to all animals, suggesting a critical importance for the meiotic program, but has been lost in many lineages with surprisingly little effect on meiosis success. However, it is unclear whether the function of PRDM9 described in mammals is shared by other species. To investigate this, we analyzed the recombination landscape of several salmonids, the genome of which harbors one full-length PRDM9 and several truncated paralogs. We identified recombination initiation sites in Oncorhynchus mykiss by mapping meiotic DNA double-strand breaks (DSBs). We found that DNA DSBs clustered at hotspots positioned away from promoters, enriched for the H3K4me3 and H3K4me36 marks and the location of which depended on the genotype of full-length Prdm9. We observed a high level of polymorphism in the zinc finger domain of full-length Prdm9, but not of the truncated paralogs. Moreover, population-scaled recombination maps in O. mykiss, Oncorhynchus kisutch and Salmo salar revealed a rapid turnover of recombination hotspots caused by PRDM9 target motif erosion. Our results imply that PRDM9 function is conserved across vertebrates and that the peculiar evolutionary runaway caused by PRDM9 has been active for several hundred million years.

Understanding the Genetic Basis of Variation in Meiotic Recombination: Past, Present, and Future

“…At the time of writing, insights into the ubiquity and relative importance of PRDM9-mediated hotspots are still emerging. PRDM9 was first shown to be the major driver of hotspot positioning in humans and mice ( Baudat et al 2010 ), and there is now evidence that it is associated with hotspots in nearly all mammals, some teleost fish, turtles, snakes, and lizards ( Baker et al 2017 ; Schield et al 2020 ; Hoge et al 2024 ; Raynaud et al 2024 ); there is also emerging evidence that PRDM9 may direct hotspot positioning in some insects ( Everitt et al 2024 ). However, PRDM9 function has been lost in some groups, such as canids, birds, crocodiles, and amphibians ( Baker et al 2017 ), which have reverted back to the stable, ancestral hotspots enriched at functional elements ( Singhal et al 2015 ).…”