Genetic basis of X-Y chromosome dissociation and male sterility in interspecific hybrids

Abstract

A high frequency of X-Y chromosome dissociation (95%) was found at first meiotic metaphase (MI) in spermatocytes of interspecific hybrids between laboratory mice, C57BL/6J (BL/6) and Mus spretus, compared with an X-Y dissociation frequency of only 3-4% in parental mice. The X-Y dissociation in F1 hybrids occurred before diakinesis rather than as a precocious dissociation at MI. The high X-Y dissociation was accompanied by spermatogenic breakdown after MI, resulting in male sterility. All F1 males were sterile and approximately half of the backcross males from fertile F1 females crossed with either BL/6 or M. spretus males were sterile. Male sterility was highly correlated with X-Y dissociation in both backcrosses. All of the mice with high X-Y dissociation were sterile and all of the males with low X-Y dissociation were fertile or subfertile. This correlation suggested that genetic divergence of the X-Y pairing region could contribute to the male sterile phenotype such that the BL/6 X chromosome would not pair with the M. spretus Y chromosome. The segregation of species-type alleles of amelogenin (Amelb and Amels), a distal X chromosome locus adjacent to the X-Y pairing region, was followed in backcross males that were analyzed for X-Y dissociation and sterility (we have used Amel as the designation for the mouse amelogenin locus; the current designation for this locus is Amg). A 95% concordance between Amelb with fertility and Amels with sterility was observed in backcrosses with BL/6, whereas the converse was observed in the backcross to M. spretus. These results imply that X-Y pairing plays an important role in male fertility and suggest that genetic divergence in X-Y pairing region between Mus species can contribute to the reproductive barriers between species and the process of speciation.