Abstract
The brain, like any other organ, is sexually dimorphic. Gonadal hormones were long thought to be the main, if not the only, biological factor at the basis of brain sexual differentiation and subsequent behaviours. In the last two decades, a few studies have challenged this hormone-centred view and shown that sex chromosomes can also have an influence. However, the role of sex chromosomes is far from being understood, and the majority of these studies are based on transgenic mice, which may limit interpretations, especially when we are interested by phenotypes shaped by natural and sexual selection. The African pygmy mouse, Mus minutoides, is a wild mouse with a polygenic sex determination system, which allows to tackle these questions. In this species, there are three sex chromosomes: the classical X and Y, as well as a feminising chromosome, called X*, thus leading to three female genotypes in natural populations: XX, XX* and X*Y; males are XY. Previous studies have shown that X*Y females differ considerably from other females: they have a greater reproductive success, are more aggressive and less anxious. There is thus a dichotomy between gonadal sex and phenotypic sex that questions the direct impact of sex chromosomes on brain sexual differentiation. Here, we show that sex chromosomes influence maternal care strategies of females, rather than impacting on their quality. We have identified a candidate neural basis for some of these behaviours: the dopaminergic system. Interestingly, we also show that the latter, rather than steroid hormones, is likely to drive enhanced territorial aggression of X*Y females. Furthermore, we show that sex chromosomes have a pervasive and sometimes dominant influence on brain transcriptome differentiation. Most importantly, we show that the steady phenotypic similarities between XX and XX* females coincide with a preferential inactivation of X*, highlighting potential sexual conflicts between X and X*. Through these analyses, we were also able to identify candidate genes at the basis of females phenotypic divergences. In sum, these multidisciplinary approaches allow us to describe the genotype-phenotype relationship in the African pygmy mouse, and show that the emergence of the X* chromosome opens up avenues for the diversification of sexual phenotypes, underpinned by the new evolutionary trajectories of the sex chromosomes.