X inactivation in a mammal species with three sex chromosomes

Abstract

X inactivation is a fundamental mechanism in eutherian mammals to restore a balance of X-linked gene products between XY males and XX females. However, it has never been extensively studied in a eutherian species with a sex determination system that deviates from the ubiquitous XX/XY. In this study, we explore the X inactivation process in the African pygmy mouse Mus minutoides, that harbours a polygenic sex determination with three sex chromosomes: Y, X, and a feminizing mutant X, named X*; females can thus be XX, XX*, or X*Y, and all males are XY. Using immunofluorescence, we investigated histone modification patterns between the two X chromosome types. We found that the X and X* chromosomes are randomly inactivated in XX* females, while no histone modifications were detected in X*Y females. Furthermore, in M. minutoides, X and X* chromosomes are fused to different autosomes, and we were able to show that the X inactivation never spreads into the autosomal segments. Evaluation of X inactivation by immunofluorescence is an excellent quantitative procedure, but it is only applicable when there is a structural difference between the two chromosomes that allows them to be distinguished.

Unusual Mammalian Sex Determination Systems: A Cabinet of Curiosities

“…As in the species discussed above, it is characterized by a very high proportion of sex-reversed females (up to 60% of the females in some populations) due to a feminizing X* chromosome, which emerged at least 0.9 million years ago [60,61]. The two Xs of this species are easily told apart cytogenetically, owing to successive rearrangements, and are randomly inactivated in XX* females [62]. M. minutoides belongs to the subgenus Nannomys, known for its exceptional karyotypic variability [63].…”

Haploid selection, sex ratio bias, and transitions between sex-determining systems

“…Previous theory would predict that the dominant 433 X * chromosome (potentially an autosome that has fused with the sex chromosome) harbours female beneficial 434 alleles, driving its spread. However, XX and XX * females have similar fitness, whereas X * Y female fitness is 435 enhanced [96][97][98]. Although Y-linkage of female-beneficial alleles is counterintuitive, our model suggests that it 436 can be stably maintained when linkage is initially tight between the sex determining region and the selected locus, 437 subsequently favoring new feminizing mutations, which would be a parsimonious explanation for the spread of 438 feminizing alleles in this case.…”

Haploid selection, sex ratio bias, and transitions between sex-determining systems

“…Previous theory would predict that the dominant X* chromosome (potentially an autosome that has fused with the sex chromosome) harbours female-beneficial alleles, driving its spread. However, XX and XX* females have similar fitness, whereas X * Y female fitness is enhanced [ 96 – 98 ]. Although Y-linkage of female-beneficial alleles is counterintuitive, our model suggests that it can be stably maintained when linkage is initially tight between the sex-determining region and the selected locus, subsequently favouring new feminising mutations, which would be a parsimonious explanation for the spread of feminising alleles in this case.…”