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Mammalian X chromosome inactivation evolved as a dosage-compensation mechanism for dosage-sensitive genes on the X chromosome

E. Pessia 1 T. Makino M. Bailly-Bechet 2 A. Mclysaght Gabriel Marais 1 
1 Sexe et évolution
PEGASE - Département PEGASE [LBBE]
Abstract : How and why female somatic X-chromosome inactivation (XCI) evolved in mammals remains poorly understood. It has been proposed that XCI is a dosage-compensation mechanism 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 hypothesis"). 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 refine 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 combined data on dosage sensitivity and XCI to compute a list of candidate genes for X-aneuploidy syndromes.
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Submitted on : Wednesday, May 16, 2012 - 2:39:56 PM
Last modification on : Sunday, September 25, 2022 - 3:54:22 AM

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E. Pessia, T. Makino, M. Bailly-Bechet, A. Mclysaght, Gabriel Marais. 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, National Academy of Sciences, 2012, 109 (14), pp.5346-5351. ⟨10.1073/pnas.1116763109⟩. ⟨hal-00698392⟩

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