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    PRDM9 histone methyltransferase associates sterility of mouse subspecies hybrids with meiotic recombination




    Jiri Forejt

    Institute of Molecular Genetics of Academy of Sciences
    of the Czech Republic, Vestec, Czech Republic


    Jeudi 3 mai 2018 à 12h00


     invité par Marc Fellous & Julie Cocquet


    Institut Cochin, 22 rue Méchain, 75014 Paris
    Salle de conférence Rosalind Franklin, 2e étage

    Hybrid sterility is one of the reproductive isolation mechanisms that prevent gene flow between incipient species and enable speciation. Forty-four years ago we mapped the first hybrid sterility gene in mammals, Hybrid sterility 1 (Hst1) in crosses between closely related subspecies of mice, and in 2009 we identified the Hst1 genetic locus with Prdm9 gene1,2. Prdm9 causes infertility in male hybrids between PWD/Ph and C57BL/6J mouse strains derived from Mus m. musculus and Mus m. domesticus subspecies by interfering with homologous chromosomes pairing and synapsis3. However, within species Prdm9 determines the sites of programmed DNA double-strand breaks (DSBs) and meiotic recombination hotspots.  We investigated the relationship between meiotic chromosome pairing and hybrid sterility in intersubspecific male hybrids with stretches of intrasubspecific homology on several autosomal pairs and found that 27 Mb of intrasubspecific homology was sufficient to rescue synapsis. Moreover, fertility in hybrid males was rescued by enhancing the pairing of four chromosomes with the highest asynapis rate. Our model relates hybrid sterility to the cascade of molecular events underlying meiotic chromosome recombination and pairing. If confirmed, this model could apply to other sexually reproducing species.

    1Forejt, J., Ivanyi, P.: Genetic studies on male sterility of hybrids between laboratory and wild mice (Mus musculus L.). Genet.Res.(Camb.) 24:189-206, 1974.

    2Mihola, O., Trachtulec, Z., Vlcek, C., Schimenti, J.C., Forejt, J: A mouse speciation gene encodes a meiotic Histone H3 methyltransferase. Science, 323:373—375, 2009.

    3Bhattacharyya, T., Gregorova, S., Mihola, O., Anger, M., Sebestova, J., Denny, P., Simecek, P., Forejt, J.: Mechanistic basis of male infertility in mouse intersubspecific hybrids. Proc Natl Acad Sci USA. Feb 5;110(6):E468-77, 2013.


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