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Baudat, F.

Publications and source records attributed to Baudat, F..

3 recordsLinked to original sources

Explaining the rapid evolution of mammalian meiotic recombination proteins

Meiotic recombination -- the exchange of genetic material between parental chromosomes during gamete production -- is critical for fertility, genome stability, and evolutionary adaptation. In eukaryotes, meiotic recombination is carried out by a deeply conserved molecular machinery. Despite this conservation, the sequences of proteins involved in meiotic recombination evolve at a remarkably high rate in mammalian species. Several biological processes have been proposed to explain this rapid evolution, but none have been quantitatively tested. In this study, we analyzed the variation in evolutionary rates of 100 recombination proteins across approximately 400 placental mammals. Our results show that this rapid evolution is primarily driven by lower levels of purifying selection compared to the rest of the proteome. We show that, although selective pressures exerted on recombination proteins are generally shared across mammals, a few recombination proteins exhibit strong variation in selective pressures. Contrary to previous hypotheses, we demonstrate that chromosome number and genome-wide recombination rates do not account for much of this variation. Instead, these variations are primarily associated with chromosome pairing and synapsis proteins, which tend to experience increased selective pressures throughout mammalian evolution, especially in large and long-lived species. This pattern probably reflects more intense selection for stability of chromosome pairing proteins in the oocytes of long-lived species, in which chromosomes sometimes need to stay paired for decades.

evolutionary biology↗

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

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.

evolutionary biology↗

The FIGNL1-FIRRM complex is required to complete meiotic recombination in the mouse and prevents massive DNA damage-independent RAD51 and DMC1 loading

During meiosis, nucleoprotein filaments of the strand exchange proteins RAD51 and DMC1 are crucial for repairing SPO11-generated DNA double-strand breaks (DSBs) by homologous recombination (HR). A balanced activity of positive and negative RAD51/DMC1 regulators ensures proper recombination. Fidgetin-like 1 (FIGNL1) was previously shown to negatively regulate RAD51 in human cells. However, FIGNL1s role during meiotic recombination in mammals remains unknown. Here, we deciphered the meiotic functions of FIGNL1 and FIGNL1 Interacting Regulator of Recombination and Mitosis (FIRRM) using male germline-specific conditional knock-out (cKO) mouse models. Both FIGNL1 and FIRRM are required for completing meiotic prophase in mouse spermatocytes. Despite efficient recruitment of DMC1 on ssDNA at meiotic DSB hotspots, the formation of late recombination intermediates is defective in Firrm cKO and Fignl1 cKO spermatocytes. Moreover, the FIGNL1-FIRRM complex limits RAD51 and DMC1 accumulation on intact chromatin, independently from the formation of SPO11-catalyzed DSBs. Purified human FIGNL1{Delta}N alters the RAD51/DMC1 nucleoprotein filament structure and inhibits strand invasion in vitro. Thus, this complex might regulate RAD51 and DMC1 association at sites of meiotic DSBs to promote proficient strand invasion and processing of recombination intermediates.

genetics↗