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Originally published in Science Express on 11 December 2008
Science 16 January 2009:
Vol. 323. no. 5912, pp. 373 - 375
DOI: 10.1126/science.1163601
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Reports

A Mouse Speciation Gene Encodes a Meiotic Histone H3 Methyltransferase

Ondrej Mihola,1* Zdenek Trachtulec,1* Cestmir Vlcek,1 John C. Schimenti,2 Jiri Forejt1{dagger}

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.

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.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: jforejt{at}img.cas.cz

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