A mouse speciation gene encodes a meiotic histone H3 methyltransferase.
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.
Mihola
Ondrej
O
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Videnska 1083, 142 20 Prague, Czech Republic.
Trachtulec
Zdenek
Z
Vlcek
Cestmir
C
Schimenti
John C
JC
Forejt
Jiri
J
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D022202:Chromosomes, Artificial, Bacterial; D003433:Crosses, Genetic; D044127:Epigenesis, Genetic; D005260:Female; D005786:Gene Expression Regulation; D049810:Genetic Speciation; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006824:Hybridization, Genetic; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008540:Meiosis; D008745:Methylation; D051379:Mice; D008809:Mice, Inbred C3H; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010053:Ovary / Q000201:enzymology; D013737:Testis / Q000201:enzymology
D006657:Histones; D011495:Histone-Lysine N-Methyltransferase; C534829:prdm9 protein, mouse