ArticlePLoS genetics2015
PRDM9 drives evolutionary erosion of hotspots in Mus musculus through haplotype-specific initiation of meiotic recombination.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 150 citations in OpenAlex.
- PRDM9-mediated meiotic hotspot specification is constrained in humans despite extensive sequence diversity.bioRxiv : the preprint server for biology · 2026Article
- On the origin of PRDM9-guided recombination hotspots.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Why recombination hotspots?PLoS genetics · 2026Review
- Beyond the Prdm9 model: independent evolution of hybrid male sterility in house mice.Heredity · 2026Article
- Low-coverage whole-genome sequencing facilitates accurate and cost-effective haplotype reconstruction in complex mouse crosses.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Article
- Convergent Evolution and the Epigenome.Epigenomes · 2025Review
- Young KRAB-zinc finger gene clusters are highly dynamic incubators of ERV-driven genetic heterogeneity in mice.Nature communications · 2025Article
- Genetic polymorphisms lead to major, locus-specific, variation in piRNA production in mouse.The EMBO journal · 2025Article
- Compensatory Evolution Following Deleterious Episodes of GC-biased Gene Conversion in Rodents.Molecular biology and evolution · 2025Article
- High-recombining genomic regions affect demography inference based on ancestral recombination graphs.Genetics · 2025Article
- PRDM9 drives the location and rapid evolution of recombination hotspots in salmonid fish.PLoS biology · 2025Article
- A Minimal Hybrid Sterility Genome Assembled by Chromosome Swapping Between Mouse Subspecies (Mus musculus).Molecular biology and evolution · 2024Article
- Understanding the Genetic Basis of Variation in Meiotic Recombination: Past, Present, and Future.Molecular biology and evolution · 2024Review
- High prevalence of PRDM9-independent recombination hotspots in placental mammals.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Bridging the gap between the evolutionary dynamics and the molecular mechanisms of meiosis: A model based exploration of the PRDM9 intra-genomic Red Queen.PLoS genetics · 2024Article
- Natural variation in the zinc-finger-encoding exon of Prdm9 affects hybrid sterility phenotypes in mice.Genetics · 2024Article
- Down the Penrose stairs, or how selection for fewer recombination hotspots maintains their existence.eLife · 2023Article
- Meiotic Recognition of Evolutionarily Diverged Homologs: Chromosomal Hybrid Sterility Revisited.Molecular biology and evolution · 2023Article
- Genetic control of the pluripotency epigenome determines differentiation bias in mouse embryonic stem cells.The EMBO journal · 2022Article
- The contribution of sex chromosome conflict to disrupted spermatogenesis in hybrid house mice.Genetics · 2022Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 2 countries.
Funding
Abstract
Meiotic recombination generates new genetic variation and assures the proper segregation of chromosomes in gametes. PRDM9, a zinc finger protein with histone methyltransferase activity, initiates meiotic recombination by binding DNA at recombination hotspots and directing the position of DNA double-strand breaks (DSB). The DSB repair mechanism suggests that hotspots should eventually self-destruct, yet genome-wide recombination levels remain constant, a conundrum known as the hotspot paradox. To test if PRDM9 drives this evolutionary erosion, we measured activity of the Prdm9Cst allele in two Mus musculus subspecies, M.m. castaneus, in which Prdm9Cst arose, and M.m. domesticus, into which Prdm9Cst was introduced experimentally. Comparing these two strains, we find that haplotype differences at hotspots lead to qualitative and quantitative changes in PRDM9 binding and activity. Using Mus spretus as an outlier, we found most variants affecting PRDM9Cst binding arose and were fixed in M.m. castaneus, suppressing hotspot activity. Furthermore, M.m. castaneus×M.m. domesticus F1 hybrids exhibit novel hotspots, with large haplotype biases in both PRDM9 binding and chromatin modification. These novel hotspots represent sites of historic evolutionary erosion that become activated in hybrids due to crosstalk between one parent's Prdm9 allele and the opposite parent's chromosome. Together these data support a model where haplotype-specific PRDM9 binding directs biased gene conversion at hotspots, ultimately leading to hotspot erosion.
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