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Evidence for dosage compensation between the X chromosome and autosomes in mammals

Nature Genetics volume 43, pages 1167–1169 (2011)Cite this article

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It has been hypothesized that, in addition to the inactivation of one of the female X chromosomes, X-linked expression in mammals is regulated through dosage compensation that involves a twofold upregulation of expression from the active X chromosome. This idea was initially based on evolutionary arguments and has subsequently been supported by the analysis of microarray expression data, which suggested that the median transcriptional magnitude of genes on the single active X chromosome is similar to that of genes on the two-copy autosomes (X:AA ratio of ∼1)1,2. However, in a recent Nature Genetics article, Xiong et al. state, on the basis of their examination of multiple human and mouse RNA sequencing (RNA-seq) data sets, that global X-chromosome upregulation is absent, thus necessitating a major revision of the current model3. The authors argue that the increased accuracy of the RNA-seq data reveals the true X:AA ratio to be close to 0.5, about half of the value obtained by examining microarray data. Here we contend that the low estimate of the X:AA ratio by Xiong et al. stems from the disproportionate contribution of transcriptionally inactive genes, which are not relevant for the evaluation of dosage compensation mechanisms, to the X chromosome average. We show that when only active genes are considered, the RNA-seq data give X:AA ratios closer to 1, and the observed minor deviation of the X:AA ratio from 1 is within the range expected when taking into account chromosome-to-chromosome variability.

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Figure 1: Transcriptional upregulation of genes on the active X chromosome.

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Acknowledgements

We thank M. Kuroda, E. Larschan, M. Gelart, C. Wang and J. Lee for helpful discussions and a critical reading of the manuscript.

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Authors and Affiliations

  1. Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts, USA

    Peter V Kharchenko, Ruibin Xi & Peter J Park

  2. Informatics Program, Children's Hospital Boston, Boston, Massachusetts, USA

    Peter V Kharchenko & Peter J Park

  3. Division of Genetics, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Peter J Park

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  1. Peter V Kharchenko
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  2. Ruibin Xi
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Correspondence to Peter J Park.

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Kharchenko, P., Xi, R. & Park, P. Evidence for dosage compensation between the X chromosome and autosomes in mammals. Nat Genet 43, 1167–1169 (2011). https://doi.org/10.1038/ng.991

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