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Published Online December 11, 2008
Science DOI: 10.1126/science.1163601

Reports

Submitted on July 22, 2008
Accepted on October 21, 2008

A Mouse Speciation Gene Encodes a Meiotic Histone H3 Methyltransferase

Ondrej Mihola 1{dagger}, Zdenek Trachtulec 1{dagger}, Cestmir Vlcek 1, John C. Schimenti 2, Jiri Forejt 1*

1 Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic
2 Center for Vertebrate Genomics, Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, T9014A Vet Research Tower, Ithaca, NY 14853, USA

* To whom correspondence should be addressed.
Jiri Forejt , E-mail: jforejt{at}img.cas.cz

{dagger}These authors contributed equally to this work.

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" Hst1f allele. Sterile hybrids display down-regulated microrchidia 2B (Morc2b) and fail to compartmentalize {gamma}H2AX 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.


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Science. ISSN 0036-8075 (print), 1095-9203 (online)