Speciation genes restrict gene flow between the incipient species and related taxa. Three decades ago, we mapped a mammalian speciation gene, hybrid sterility 1 (Hst1), in the intersubspecific hybrids of house mouse. Here, we identify this gene as Prdm9, encoding a histone H3 lysine 4 trimethyltransferase. We rescued infertility in male hybrids with bacterial artificial chromosomes carrying Prdm9 from a strain with the "fertility" Hst1(f) allele. Sterile hybrids display down-regulated microrchidia 2B (Morc2b) and fail to compartmentalize gammaH2AX into the pachynema sex (XY) body. These defects, seen also in Prdm9-null mutants, are rescued by the Prdm9 transgene. Identification of a vertebrate hybrid sterility gene reveals a role for epigenetics in speciation and opens a window to a hybrid sterility gene network.

Institute of Molecular Genetics Academy of Sciences of the Czech Republic Videnska 1083 142 20 Prague Czech Republic

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Science. 2009 Jan 16;323(5912):350-1. doi: 10.1126/science.1169442. PubMed

References provided by Crossref.org

Phenogenomic resources immortalized in a panel of wild-derived strains of five species of house mice

A Minimal Hybrid Sterility Genome Assembled by Chromosome Swapping Between Mouse Subspecies (Mus musculus)

Natural variation in the zinc-finger-encoding exon of Prdm9 affects hybrid sterility phenotypes in mice

Meiotic Recognition of Evolutionarily Diverged Homologs: Chromosomal Hybrid Sterility Revisited

Prdm9 deficiency of rat oocytes causes synapsis among non-homologous chromosomes and aneuploidy

Meiotic chromosome dynamics and double strand break formation in reptiles

Genic and chromosomal components of Prdm9-driven hybrid male sterility in mice (Mus musculus)

Rat PRDM9 shapes recombination landscapes, duration of meiosis, gametogenesis, and age of fertility

Chromosome-wide characterization of meiotic noncrossovers (gene conversions) in mouse hybrids

Chromosomal evolution in Raphicerus antelope suggests divergent X chromosomes may drive speciation through females, rather than males, contrary to Haldane's rule

Prdm9 Intersubspecific Interactions in Hybrid Male Sterility of House Mouse

Copy-number variation introduced by long transgenes compromises mouse male fertility independently of pachytene checkpoints

Genomic Structure of Hstx2 Modifier of Prdm9-Dependent Hybrid Male Sterility in Mice

Histone methyltransferase PRDM9 is not essential for meiosis in male mice

Cisplatin-induced DNA double-strand breaks promote meiotic chromosome synapsis in PRDM9-controlled mouse hybrid sterility

Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice

Genomic islands of differentiation in two songbird species reveal candidate genes for hybrid female sterility

Conservation of the Red Kite Milvus milvus (Aves: Accipitriformes) Is Not Affected by the Establishment of a Broad Hybrid Zone with the Black Kite Milvus migrans migrans in Central Europe

Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse

Multimer Formation Explains Allelic Suppression of PRDM9 Recombination Hotspots