PRDM9 Is a Major Determinant of Meiotic Recombination Hotspots in Humans and Mice
Open accessAbstract
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.
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Using DSB maps and a maximum likelihood model, only 5.9% (2 log unit CI 0-24%) of observed PRDM9 knockout duo maternal gamete crossovers matched DSB sites from wild type PRDM9-A allele homozygotes.
“Using double strand break (DSB) maps and a maximum likelihood model to account for variability in region size and hotspot density(18), we estimated that only 5.9% (2 log unit confidence interval: 0 - 24%) of the observed PRDM9 knockout duo maternal gamete crossovers matched DSB sites from wild type PRDM9-A allele homozygotes(5).”
From Health and population effects of rare gene knockouts in adult humans with related parents (2016) · cites this paper as [18]
PRDM9 is the major known determinant of the genomic locations of meiotic recombination events in humans and mice through its DNA binding site zinc finger domain.
“PRDM9 is the major known determinant of the genomic locations of meiotic recombination events in humans and mice through its DNA binding site zinc finger domain (6, 18, 19).”
From Health and population effects of rare gene knockouts in adult humans with related parents (2016) · cites this paper as [18]
18.5% of crossovers in the PRDM9 knockout duo (CI 1%-42%) occurred in linkage disequilibrium based hotspots versus 75.7% in the control duo (CI 57%-89%).
“Using similar methods we saw that 18.5% of crossovers observed in the PRDM9 knockout duo (confidence interval: 1% - 42%) occurred in linkage disequilibrium based hotspots versus 75.7% in the control duo (confidence interval 57%-89% consistent with a previously published estimate of an average of 60% of crossovers occurring at hotspots(18))(5).”
From Health and population effects of rare gene knockouts in adult humans with related parents (2016) · cites this paper as [18]
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- Authors
- Baudat, F., Buard, J., Grey, C., Fledel-Alon, A., Ober, C., Przeworski, M., Coop, G., & de Massy, B.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Chicago (US)
- Howard Hughes Medical Institute (US)
- University of California, Davis (US)
- Institut de Génétique Humaine, UPR1142, CNRS, Montpellier, France.
- Corresponding author
- Baudat, F.
- Buard, J.
- Grey, C.
- Venue
- Science
- Published
- 2010-02-12
- Volume
- 327
- Issue
- 5967
- Pages
- 836-840
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4295902
- OpenAlex
- W2047657819
- Cited by
- 1,026
- References
- 31
- Citations by year
- 2026: 49 · 2025: 51 · 2024: 55 · 2023: 46 · 2022: 57 · 2021: 51 · 2020: 55 · 2019: 49 · 2018: 68 · 2017: 63 · 2016: 77 · 2015: 60 · 2014: 80 · 2013: 58 · 2012: 87
- FWCI
- 27.56
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Agence Nationale de la Recherche (ANR-09-BLAN-0269)
- U.S. Public Health Service
- National Heart, Lung, and Blood Institute (HL085197, R01HL085197)
- National Institute of General Medical Sciences (R01GM083098, GM83098)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD021244, HD21244)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- PRDM9, meiotic recombination hotspots, histone methyltransferase, DNA sequence motifs, chromatin modification, allelic variation, human-chimpanzee comparison, protein-DNA interactions, meiosis
- MeSH terms
- Alleles, Amino Acid Sequence, Animals, Base Sequence, Binding Sites, DNA, DNA-Binding Proteins, Genotype, Humans, Meiosis, Mice, Inbred C57BL, Molecular Sequence Data, Phenotype, Histone-Lysine N-Methyltransferase, Recombination, Genetic, Genome, Human, Zinc Fingers, Genome, Mice, DNA Breaks, Double-Stranded
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