Memories of an X-chromosome

Heterogametic sex determination systems, where one sex is homogametic –XX or ZZ– and the other is heterogametic –XY or ZW–, entail a transcriptional dosage problem: in the absence of a compensatory mechanism, the homogametic sex expresses a double dose of those genes allocated on the duplicated sex chromosome. Eutherian mammals have evolved an epigenetic-based compensatory mechanism, termed X-chromosome inactivation (XCI) (1) that ensures that most X-linked genes are equally expressed in male (XY) and female (XX) individuals. In these species, XCI occurs randomly in the paternal or maternally inherited X-chromosome in such a way that females can be considered as mosaic individuals, expressing the paternally inherited X-chromosome in half of their cells and the maternally inherited one in the other half. The random nature of XCI confers an evolutionary advantage to females, as deleterious or detrimental mutations on one of the X-chromosomes, which can be somehow compensated by the cells expressing the “healthy” allele.