The X chromosomes of therian (marsupial and eutherian) mammals share a common evolutionary origin, with the marsupial X corresponding to approximately two-thirds of the human X chromosome. Inactivation of the X chromosome in female somatic cells is observedin both of these mammalian lineages and is presumed to have evolved in the therian ancestor to compensate for X-gene dosage differences between XY males and XX females. In the 50 years since Mary Lyon’s landmark publication on the hypothesis of X chromosome inactivation (XCI), we are still struggling to unravel the evolution of this fascinating silencing mechanism. Ohno proposed that dosage compensation for X-borne genes required up regulation to restore the X to autosome transcription ratio to one in males.
This in turn led to an over expression of X-borne genes in females, which was counteracted by XCI.By using RNA-FISH, a technique that permits the visualization of X-borne gene primary transcripts in single cells, it is evident that there are similarities between marsupials and eutherians. Genes on the marsupial X show a reproducible frequency of cells with monoallelic or biallelic expression. This was also observed for genes escaping inactivation in three distantly related eutherian species (human, mouse and elephant), particularly for genes in the region added to the X chromosome in the eutherian lineage.
This is similar to the pattern of expression observed for genes on the multiple X chromosomes of a monotreme mammal, the platypus, the X chromosomes of which share no homology to the therian X. It has been proposed that this type of probabilistic expression represents an ancient method of silencing from which XCI arose. Comparisons of distantly related species suggest that there are some common features of XCI between both lineages and support the idea of a common origin of XCI. Future research should continue to compare XCI in diverse species, if we are to unravel the mysteries behind the evolution of this remarkable epigenetic mechanism.
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