Drive against hotspot motifs in primates implicates the PRDM9 gene in meiotic recombination.
Although present in both humans and chimpanzees, recombination hotspots, at which meiotic crossover events cluster, differ markedly in their genomic location between the species. We report that a 13-base pair sequence motif previously associated with the activity of 40% of human hotspots does not function in chimpanzees and is being removed by self-destructive drive in the human lineage. Multiple lines of evidence suggest that the rapidly evolving zinc-finger protein PRDM9 binds to this motif and that sequence changes in the protein may be responsible for hotspot differences between species. The involvement of PRDM9, which causes histone H3 lysine 4 trimethylation, implies that there is a common mechanism for recombination hotspots in eukaryotes but raises questions about what forces have driven such rapid change.
Myers
Simon
S
Department of Statistics, Oxford University, 1 South Parks Road, Oxford OX1 3TG, UK. myers@stats.ox.ac.uk
Bowden
Rory
R
Tumian
Afidalina
A
Bontrop
Ronald E
RE
Freeman
Colin
C
MacFie
Tammie S
TS
McVean
Gil
G
Donnelly
Peter
P
D000818:Animals; D001483:Base Sequence; D003434:Crossing Over, Genetic; D004247:DNA / Q000378:metabolism; D019143:Evolution, Molecular; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008540:Meiosis / Q000235:genetics*; D008745:Methylation; D002679:Pan troglodytes / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011995:Recombination, Genetic; D013045:Species Specificity
D006657:Histones; D004247:DNA; D011495:Histone-Lysine N-Methyltransferase; C544431:PRDM9 protein, human