Prdm9 incompatibility controls oligospermia and delayed fertility but no selfish transmission in mouse intersubspecific hybrids

PLoS One. 2014 Apr 22;9(4):e95806. doi: 10.1371/journal.pone.0095806. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Alleles
  • Animals
  • Chromosomes, Mammalian
  • Crosses, Genetic*
  • Female
  • Gene Dosage
  • Genotype
  • Histone-Lysine N-Methyltransferase / genetics*
  • Infertility, Male / genetics*
  • Male
  • Meiosis
  • Mice
  • Oligospermia / genetics*
  • Phenotype
  • Quantitative Trait Loci
  • Testis / metabolism
  • Testis / pathology


  • Histone-Lysine N-Methyltransferase
  • prdm9 protein, mouse

Grants and funding

PhD studies of PF and TB were supported in part by the Faculty of Science, Charles University, Prague. This work was also supported by the Czech Science Foundation grants nos. P305/10/1931 (ZT), 13-08078S (JF), P305/11/P605 (OM), and 206/08/0640 (JP), and by the Academy of Sciences of the Czech Republic (RVO 68378050; Premium Academiae to JF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.