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RNA sequencing shows no dosage compensation of the active X-chromosome

Abstract

Mammalian cells from both sexes typically contain one active X chromosome but two sets of autosomes. It has previously been hypothesized that X-linked genes are expressed at twice the level of autosomal genes per active allele to balance the gene dose between the X chromosome and autosomes (termed 'Ohno's hypothesis'). This hypothesis was supported by the observation that microarray-based gene expression levels were indistinguishable between one X chromosome and two autosomes (the X to two autosomes ratio (X:AA) 1). Here we show that RNA sequencing (RNA-Seq) is more sensitive than microarray and that RNA-Seq data reveal an X:AA ratio of 0.5 in human and mouse. In Caenorhabditis elegans hermaphrodites, the X:AA ratio reduces progressively from 1 in larvae to 0.5 in adults. Proteomic data are consistent with the RNA-Seq results and further suggest the lack of X upregulation at the protein level. Together, our findings reject Ohno's hypothesis, necessitating a major revision of the current model of dosage compensation in the evolution of sex chromosomes.

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Figure 1: Comparison of gene expressions measured by microarray and RNA-Seq6,11,12,13.
Figure 2: Comparisons of RNA-Seq gene expression levels between the X chromosome and autosomes in 12 human tissues and 3 mouse tissues11,12,13,16.
Figure 3: Comparison of RNA-Seq gene expression levels of the X chromosome and autosomes in C. elegans19.

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Acknowledgements

We thank B.-Y. Liao for sharing his processed mouse proteomic data, Y. Jiang for assistance in statistical analysis and B.-Y. Liao, J. Lu, O. Podlaha, P. Shi, W. Qian, C.-I. Wu and Y. Xing for valuable comments. Part of the work was conducted in the laboratory of Peng Shi at the State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology. This work was supported by research grants from the US National Institutes of Health (to J.Z.), the National Natural Science Foundation of China (90717115 and 30871371 to X.H.; 11001280 to Xueqin Wang) and the Tianyuan Fund for Mathematics (10926200 to Xueqin Wang).

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X.H. and J.Z. conceived the study. Y.X., X.C. and Z.C. produced data. X.H., X.C., Y.X., J.Z., Xunzhang Wang, S.S. and Xueqin Wang analyzed data. X.H., Xunzhang Wang and S.S. provided reagents. X.H. and J.Z. wrote the paper.

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Correspondence to Jianzhi Zhang or Xionglei He.

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The authors declare no competing financial interests.

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Supplementary Tables 1–15 and Supplementary Figures 1–5. (PDF 1085 kb)

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Xiong, Y., Chen, X., Chen, Z. et al. RNA sequencing shows no dosage compensation of the active X-chromosome. Nat Genet 42, 1043–1047 (2010). https://doi.org/10.1038/ng.711

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