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Claims and counterclaims of X-chromosome compensation

Nature Structural & Molecular Biology volume 19, pages 3–5 (2012)Cite this article

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Is there upregulation of the single active X chromosome in mammals or not? Recent studies take different points of view.

Before delving into the different views, let us examine two assumptions commonly made about dosage compensation that are not necessarily true. First, it is often assumed that most gene products encoded on a varied chromosome need to be in the proper stoichiometric relationship with others from across the genome. Evidence from experimental, clinical, population and evolutionary studies suggest that the most critical dosage-sensitive genes are those that are components of macromolecular complexes, including transcription factors and signal transduction pathway components10,11,12,13,14. Indeed, the inclusion of these genes as components of macromolecular machines contributes to their dosage sensitivity11,12. The change in the dosage of these classes of gene products appears to have the greatest impact on evolutionary fitness and on the phenotype13,14. Of course, regulatory genes produce their effects through their impact on downstream targets, and how this relationship affects fitness and the phenotype has not been explored to a large extent. Nevertheless, the dosage of specific classes of genes is likely to be the driver in the evolution of special mechanisms involved with dosage compensation. Specialized compensation mechanisms are as much about preventing havoc across the genome as about modulating the expression of the varied chromosome itself. Failure to upregulate other classes of genes might be without major consequences, although they could still be upregulated incidentally by mechanisms selected to operate on the dosage-critical genes.

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Figure 1: Ohno's proposed evolution of mammalian sex chromosomes.

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  1. James A. Birchler is in the Division of Biological Sciences, University of Missouri, Columbia, Missouri, USA.,

    James A Birchler

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Correspondence to James A Birchler.

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Birchler, J. Claims and counterclaims of X-chromosome compensation. Nat Struct Mol Biol 19, 3–5 (2012). https://doi.org/10.1038/nsmb.2218

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