title: Prdm9 incompatibility controls oligospermia and delayed fertility but no selfish transmission in mouse intersubspecific hybrids.
abstract: PR-domain 9 (Prdm9) is the first hybrid sterility gene identified in mammals. The incompatibility between Prdm9 from Mus musculus domesticus (Mmd; the B6 strain) and the Hstx2 region of chromosome (Chr) X from M. m. musculus (Mmm; the PWD strain) participates in the complete meiotic arrest of mouse intersubspecific (PWD×B6)F1 hybrid males. Other studies suggest that also semisterile intersubspecific hybrids are relevant for mouse speciation, but the genes responsible remain unknown. To investigate the causes of this semisterility, we analyzed the role of Prdm9 and Chr X in hybrids resulting from the crosses of PWK, another Mmm-derived inbred strain. We demonstrate that Prdm9 and Chr X control the partial meiotic arrest and reduced sperm count in (PWK×B6)F1 males. Asynapsis of heterosubspecific chromosomes and semisterility were partially suppressed by removal of the B6 allele of Prdm9. Polymorphisms between PWK and PWD on Chr X but not in the Prdm9 region were responsible for the modification of the outcome of Prdm9-Chr X F1 hybrid incompatibility. Furthermore, (PWK×B6)F1 hybrid males displayed delayed fertility dependent on the Prdm9 incompatibility. While the Drosophila hybrid sterility gene Overdrive causes both delayed fertility and increased transmission of its own chromosome to the offspring, the segregation of Chr X and the Prdm9 region from the mouse (PWK×B6)F1 males was normal. Our results indicate extended functional consequences of Prdm9-Chr X intersubspecific incompatibility on the fertility of hybrids and should influence the design of fertility analyses in hybrid zones and of laboratory crosses between Mmm and Mmd strains.
authors.affiliation: Department of Mouse Molecular Genetics, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Flachs
authors.affiliation: Department of Mouse Molecular Genetics, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
authors.forename: Tanmoy
authors.initials: T
authors.lastname: Bhattacharyya
authors.affiliation: Department of Mouse Molecular Genetics, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
authors.forename: Ondřej
authors.initials: O
authors.lastname: Mihola
authors.affiliation: Research Facility Studenec, Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Piálek
authors.affiliation: Department of Mouse Molecular Genetics, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Forejt
authors.affiliation: Department of Mouse Molecular Genetics, Institute of Molecular Genetics of the Academy of Sciences of the Czech Republic, v.v.i., Prague, Czech Republic.
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Trachtulec
mesh_terms: D000367:Age Factors; D000483:Alleles; D000818:Animals; D033481:Chromosomes, Mammalian; D003433:Crosses, Genetic; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D007248:Infertility, Male / Q000235:genetics*; D008297:Male; D008540:Meiosis; D051379:Mice; D009845:Oligospermia / Q000235:genetics*; D010641:Phenotype; D040641:Quantitative Trait Loci; D013737:Testis / Q000378:metabolism / Q000473:pathology
chemical_list: D011495:Histone-Lysine N-Methyltransferase; C534829:prdm9 protein, mouse
references.citation: Mamm Genome. 2009 Feb;20(2):83-91
references.pmid: 19123034
references.citation: Science. 2006 Sep 8;313(5792):1448-50
references.pmid: 16960009
references.citation: Evolution. 1991 Mar;45(2):262-267
references.pmid: 28567880
references.citation: Genome Res. 2008 Mar;18(3):509-15
references.pmid: 18256238
references.citation: Dev Growth Differ. 1993 Jun;35(3):271-281
references.pmid: 37281282
references.citation: Genomics. 1994 Sep 1;23(1):132-7
references.pmid: 7829061
references.citation: Science. 2009 Jan 16;323(5912):373-5
references.pmid: 19074312
references.citation: Nature. 2011 Sep 14;477(7364):289-94
references.pmid: 21921910
references.citation: BMC Genomics. 2007 Jan 18;8:20
references.pmid: 17233890
references.citation: J Hered. 2008 Jan-Feb;99(1):34-44
references.pmid: 17965200
references.citation: Science. 2010 Feb 12;327(5967):835
references.pmid: 20044538
references.citation: Evolution. 2011 Apr;65(4):993-1010
references.pmid: 21463294
references.citation: Mol Ecol. 2012 Jun;21(12):3032-47
references.pmid: 22582810
references.citation: Nat Genet. 2011 May 29;43(7):648-55
references.pmid: 21623374
references.citation: Folia Biol (Praha). 2000;46(1):31-41
references.pmid: 10730880
references.citation: PLoS Genet. 2014 Feb 06;10(2):e1004088
references.pmid: 24516397
references.citation: Nature. 2012 May 13;485(7400):642-5
references.pmid: 22660327
references.citation: Evolution. 2004 Sep;58(9):2064-78
references.pmid: 15521462
references.citation: Nat Genet. 2004 Nov;36(11):1133-7
references.pmid: 15514660
references.citation: Evolution. 2008 Jan;62(1):50-65
references.pmid: 18005156
references.citation: Mamm Genome. 2004 Jul;15(7):515-24
references.pmid: 15366371
references.citation: Genet Res. 1974 Oct;24(2):189-206
references.pmid: 4452481
references.citation: Genetics. 2007 Jan;175(1):185-97
references.pmid: 17057240
references.citation: Chromosoma. 1993 Jan;102(2):71-80
references.pmid: 8432196
references.citation: Science. 1998 Nov 20;282(5393):1501-4
references.pmid: 9822383
references.citation: Genetics. 1991 Aug;128(4):841-58
references.pmid: 1916248
references.citation: PLoS Genet. 2012;8(11):e1003044
references.pmid: 23133405
references.citation: Genetics. 2004 Feb;166(2):913-24
references.pmid: 15020476
references.citation: Mamm Genome. 1996 Feb;7(2):107-13
references.pmid: 8835526
references.citation: Evolution. 2012 Nov;66(11):3321-35
references.pmid: 23106700
references.citation: Proc Biol Sci. 2012 Dec 7;279(1748):4803-10
references.pmid: 23055063
references.citation: Science. 2009 Jan 16;323(5912):376-9
references.pmid: 19074311
references.citation: Mamm Genome. 1999 Oct;10(10):958
references.pmid: 10501959
references.citation: Science. 2010 Feb 12;327(5967):836-40
references.pmid: 20044539
references.citation: Genetics. 2010 Sep;186(1):339-51
references.pmid: 20610405
references.citation: Evolution. 2012 Feb;66(2):443-58
references.pmid: 22276540
references.citation: Nature. 2005 Nov 17;438(7066):374-8
references.pmid: 16292313
references.citation: Genetics. 1999 Apr;151(4):1569-79
references.pmid: 10101178
references.citation: Genetics. 2011 Sep;189(1):289-304
references.pmid: 21750261
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):E468-77
references.pmid: 23329330
references.citation: Genetics. 2008 Mar;178(3):1777-84
references.pmid: 18245833
references.citation: Nat Genet. 2005 Jan;37(1):41-7
references.pmid: 15580272