Man to Mouse—Lessons Learned from the Distal End of the Human X Chromosome

Conservation between human and murine X chromosomes has been accepted as an incontrovertible principle for a long time and was generally envisaged as a powerful model system for the evolution of vertebrate sex chromosomes. In fact, the original postulate of Ohno (1973) that the constraints imposed by X-inactivation would conserve genes on the mammalian X chromosomes was reevaluated to become a fundamental law underlying sex chromosome evolution. Contrasting this overall picture of harmony, the most distal band of the human X chromosome (Xp22.3) reveals a unique and so far unprecedented picture of chromosomal rearrangements during the evolution in eutherian mammals. The result of efforts toward the mapping of murine homologs of human X chromosomal genes have not only illustrated the massive reshuffling of X chromosomes during their evolution but also refined our understanding of mouse models for certain X chromosomal human genetic disorders.