Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome.
Item Type:Journal Article
Citation:Pessia E, Makino T, Bailly-Bechet M, McLysaght A, Marais GA, Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome., Proceedings of the National Academy of Sciences of the United States of America, 109, 14, 2012, 5346-5351
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How and why female somatic X-chromosome inactivation (XCI) evolved in mammals remains poorly understood. Ohno proposed a two-step process where XCI is a dosage-compensation mechaQ: 7 nism that evolved to equalize expression levels of X-linked genes in females (2X) and males (1X), with a prior twofold increase in expression of X-linked genes in both sexes [Ohno S (1967) (Springer, Berlin)]. Whereas the parity of X chromosome expression between the sexes has been clearly demonstrated, tests for the doubling of expression levels globally along the X chromosome have returned contradictory results. However, changes in gene dosage during sex-chromosome evolution are not expected to impact on all genes equally, and should have greater consequences for dosage-sensitive genes. We show that, for genes encoding components of large protein complexes (! 7 members)?a class of genes that is expected to be dosage-sensitive?expression of X-linked genes is similar to that of autosomal genes within the complex. These data support Ohno?s hypothesis that XCI acts as a dosage-compensation mechanism, and allow us to re!ne Ohno?s model of XCI evolution. We also explore the contribution of dosage- sensitive genes to X aneuploidy phenotypes in humans, such as Turner (X0) and Klinefelter (XXY) syndromes. X aneuploidy in humans is common and is known to have mild effects because most of the supernumerary X genes are inactivated and not affected by aneuploidy. Only genes escaping XCI experience dosage changes in X-aneuploidy patients. We sensitivity and XCI to compute a list of candidate genes for Xaneuploidy syndromes.
Author: MC LYSAGHT, AOIFE
Type of material:Journal Article
Series/Report no:Proceedings of the National Academy of Sciences of the United States of America;
Availability:Full text available