Drive Against Hotspot Motifs in Primates Implicates the PRDM9 gene in Meiotic Recombination
By S. Myers, R. Bowden, A. Tumian, R. Bontrop, C. Freeman, T. Macfie, G. McVean, Peter Donnelly. Science, 2009
676 citations recorded by the source corpus.
Homing in on Hotspots The clustering of recombination in the genome, around locations known as hotspots, is associated with specific DNA motifs. Now, using a variety of techniques, three studies implicate a chromatin-modifying protein, the histone-methyltransferase PRDM9, as a major factor involved in human hotspots (see the Perspective by Cheung et al.). Parvanov et al. (p. 835, published online 31 December) mapped the locus in mice, and analyzed allelic variation in mice and humans, whereas Myers et al. (p. 876, published online 31 December) used a comparative analysis between human and chimpanzees to show that the recombination process leads to a self-destructive drive in which the very motifs that recruit hotspots are eliminated from our genome. Baudat et al. (p. 836, published online 31 December) took this analysis a step further to identify human allelic variants within Prdm9 that differed in the frequency at which they used hotspots. Furthermore, differential binding of this protein to different human alleles suggests that this protein interacts with specific DNA sequences. Thus, PDRM9 functions in the determination of recombination loci within the genome and may be a significant factor in the genomic differences between closely related species. Bioinformatics identifies a chromatin-modifying enzyme as a factor in determining recombination hotspots. 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.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/c3d3af18b7d3ea219f02bcfbf81f2873a36dd177
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In Molecular Biology
Citations in the corpus
- Nothing in Genetics Makes Sense Except in Light of Genomic Conflict (2013, background): “…digest, and replace—essentially guarantees that recombinational hot spots will be unstable across time due to a disadvantage in genomic conflict; alleles more prone to cutting have a molecular drive disadvantage, and this is a pattern that was recently confirmed empirically (Myers et al. 2010).”