Abstract

The two sexes have many somatic tissue differences that are due to the action of gonadal secretions. However, the genes encoded on the sex chromosomes might also have the potential to cause sex differences in development and/or function through differential expression of the X and Y homologues. A recent study demonstrates that this latter possibility could be occurring in mice [1xSex differences in sex chromosome gene expression in mouse brain. Xu, J. et al. Hum. Mol. Genet. 2002; 11: 1409–1419Crossref | PubMedSee all References][1]. Using RT–PCR and northern blot analysis, Xu et al. examined the expression of six Y genes and their X-linked homologues (Usp9y/x, Ube1y/x, Smcy/x, Eif2s3y/x, Uty/x, and Dby/x) in the brains of mice at three different stages of development: embryo day 13.5, 1 day postpartum and adult. There was more expression of the X-linked homologues in females than in males, irrespective of their X-inactivation status. Furthermore, the level of expression of the Y homologues for five of these genes was not sufficient in males to compensate for the female bias in X gene expression.In addition, two of the X–Y gene pairs (Usp9y/x and Ube1y/x) appear to be differentially regulated in a tissue-dependent manner, and one X–Y pair (Eif2s3y/x) is differentially regulated in an age-dependent manner. Hence, these three X–Y gene pairs, although assumed to be homologous, might not be functionally equivalent.Nevertheless, the differences in gene expression between X and Y homologues could in fact be due to the action of gonadal secretions. To test this, Xu et al. examined whether the expression of the six Y genes was dependent on the presence of androgens. They did this using the elegant strategy of comparing the expression in XY males and XY− females, where the Y− chromosome carries a deletion that removes the testis-determining gene Sry. The Y genes were expressed in both XY males and XY− females (but not XX female controls), indicating that expression is not in fact dependent on gonadal secretions in males, and these genes could act over and above the effects of hormones.Although somewhat unexpected, these results give rise to the possibility that, in the brain at least, there is a genetic mechanism in place that overrides any X inactivation process to generate sexual dimorphism. How these genes affect function is unclear, although there are a number of brain and behavioural outcomes, such as aggression, copulatory behaviour and hippocampal architecture, that are linked to the nonrecombining region of the Y chromosome.

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