The red queen model of recombination hotspots evolution in the light of archaic and modern human genomes.
Recombination is an essential process in eukaryotes, which increases diversity by disrupting genetic linkage between loci and ensures the proper segregation of chromosomes during meiosis. In the human genome, recombination events are clustered in hotspots, whose location is determined by the PRDM9 protein. There is evidence that the location of hotspots evolves rapidly, as a consequence of changes in PRDM9 DNA-binding domain. However, the reasons for these changes and the rate at which they occur are not known. In this study, we investigated the evolution of human hotspot loci and of PRDM9 target motifs, both in modern and archaic human lineages (Denisovan) to quantify the dynamic of hotspot turnover during the recent period of human evolution. We show that present-day human hotspots are young: they have been active only during the last 10% of the time since the divergence from chimpanzee, starting to be operating shortly before the split between Denisovans and modern humans. Surprisingly, however, our analyses indicate that Denisovan recombination hotspots did not overlap with modern human ones, despite sharing similar PRDM9 target motifs. We further show that high-affinity PRDM9 target motifs are subject to a strong self-destructive drive, known as biased gene conversion (BGC), which should lead to the loss of the majority of them in the next 3 MYR. This depletion of PRDM9 genomic targets is expected to decrease fitness, and thereby to favor new PRDM9 alleles binding different motifs. Our refined estimates of the age and life expectancy of human hotspots provide empirical evidence in support of the Red Queen hypothesis of recombination hotspots evolution.
Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, Université Lyon 1, Villeurbanne, France.
Yann
Y
Lesecque
Institut des Sciences de l'Evolution, UMR CNRS 5554, Université Montpellier 2, Montpellier, France.
Sylvain
S
Glémin
Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, Université Lyon 1, Villeurbanne, France.
Nicolas
N
Lartillot
Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, Université Lyon 1, Villeurbanne, France.
Dominique
D
Mouchiroud
Laboratoire de Biométrie et Biologie Evolutive, UMR CNRS 5558, Université Lyon 1, Villeurbanne, France.
Laurent
L
Duret
D000818:Animals; D002875:Chromosomes / Q000235:genetics; D003434:Crossing Over, Genetic; D004268:DNA-Binding Proteins; D019143:Evolution, Molecular; D005785:Gene Conversion; D015894:Genome, Human; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D008540:Meiosis / Q000235:genetics; D002679:Pan troglodytes; D011995:Recombination, Genetic
D004268:DNA-Binding Proteins; D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human