African pygmy mice: Females are XY ... researchers find out why

A team led by Frédéric Veyrunes, CNRS researcher at the Institut des Sciences de l'Evolution in Montpellier, working in collaboration with biologists from the Institut de Génomique Fonctionnelle in Lyon and the IRD, have just identified this unexpected case of sex determination. These scientists have demonstrated a particular chromosomal rearrangement on the X chromosome of this mouse. This work should provide a clearer understanding of how classic sex determination functions in mammals.

The research is published in the 7 April issue of the journal Proceedings of the Royal Society B.

In the great majority of mammals, sex determination follows a simple rule: an XX chromosome arrangement defines a female while an XY arrangement produces a male. However, some situations may deviate from this principle, in which case reference is made to chromosomal anomalies that most generally cause sterility. On the Y chromosome, sex is determined by the presence or absence of a single gene called Sry. Located in 1990, this gene initiates the development of male characteristics; without this gene, the gonads become ovaries.

However, some mammal species do not obey this rule. Until now, only seven cases of atypical sex determination had been observed, all in rodents. The team coordinated by Frédéric Veyrunes has just identified a new case, the first to be described for 30 years, in Mus minutoides, an African pygmy mouse species which is particularly interesting as it is very closely related to the house mouse, the principal mammal model used in biology. By studying different populations of African Mus minutoides, the researchers observed a very high proportion of fertile females carrying XY chromosomes (between 74% and 100%).

In order to better understand the situation at a genetic level, the scientists performed molecular and cytogenetic analyses, and revealed that sex reversion did not appear to be induced by a mutation on the Sry gene but by an as yet unknown chromosomal rearrangement on the X chromosome. Indeed, two morphologically indistinguishable X chromosomes were present in the females: X and X*. One of them, named X*, was invariably associated with females carrying the X*Y pair. It bore a mutation causing a reversion of sex. It was quite surprising that the mutation was carried by the X rather than the Y chromosome, which generally determines gender. But the X chromosome of mammals also carries numerous genes that control sexual and reproductive traits, some of which are expressed at spermatogenesis. One question remains: why have these XY mice not disappeared as a result of natural selection? Several hypotheses have been put forward to explain this evolutionary paradox and are now being explored in more detail.

These aberrant systems are a subject of little study, and the mechanisms that explain these anomalies and their functioning remain almost unknown. Greater knowledge of them might enable a clearer understanding of "classic" sex determination in mammals. Indeed, most of the major advances in this area have arisen from the analysis of variant sex systems and pathological sex reversions in humans and mice.