Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice

It has been known for centuries that hybrids between closely related species are often infertile. This hybrid sterility was an enigma for Charles Darwin, who understood that it influenced how new species formed but could not fit it with his theory of evolution by natural selection. Sex cells – in mammals, the egg or sperm cells – form by a process called meiosis. During meiosis, chromosomes formed of DNA inherited from the mother pair up with the equivalent chromosomes inherited from the father and exchange sections of their DNA. This process is called synapsis and homologous recombination. A gene called Prdm9 determines where the DNA will break and recombine. Prdm9 plays a major role in determining whether the male hybrid offspring of two laboratory strains of mice (which come from different subspecies) are sterile. In sterile hybrids, the two versions of Prdm9 interact in ways that disturb the DNA repair process. However, these interactions are not enough on their own to cause hybrid males to be sterile. The currently prevailing view is that interactions between a large number of other – currently unidentified – genes also contribute to sterility. But could there be other processes involved that do not involve gene interactions? To investigate, Gregorova, Gergelits et al. utilized strains of hybrid mice where a pair of chromosomes of one subspecies was substituted by the corresponding pair from the other subspecies. This generated hybrids with stretches of DNA that came entirely from a single subspecies. Having such a stretch that lasted for 27 million or more DNA base pairs fully restored synapsis in a given pair of chromosomes during meiosis. Hybrid sterility was reversed when synapsis was restored in the four chromosomes that were most strongly affected by synapsis not occurring. The results presented by Gregorova, Gergelits et al. provide a direct link between Prdm9-controlled chromosome synapsis and the interruption of meiosis. Hybrid sterility occurs in all sexually reproducing organisms, as does chromosome pairing during meiosis. Thus Prdm9 could control a particular case of a more universal mechanism that enables new species to form.