State Key Laboratory of Biocontrol, College of Life Sciences, Sun Yat-sen University, Guangzhou, China.
Nat Genet. 2010 Dec;42(12):1043-7. doi: 10.1038/ng.711.
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.
哺乳动物的雌雄细胞通常都含有一条活性 X 染色体和两套常染色体。先前的假说认为，X 连锁基因在每个活性等位基因上的表达水平是常染色体基因的两倍，以平衡 X 染色体和常染色体之间的基因剂量（称为“大野假说”）。这一假说得到了支持，因为基于微阵列的基因表达水平在一条 X 染色体和两条常染色体之间是无法区分的（X 染色体与两条常染色体的比值（X:AA）1）。在这里，我们表明 RNA 测序（RNA-Seq）比微阵列更敏感，并且 RNA-Seq 数据显示人类和小鼠的 X:AA 比值约为 0.5。在秀丽隐杆线虫雌雄同体中，X:AA 比值从幼虫时的1 逐渐降低到成虫时的~0.5。蛋白质组学数据与 RNA-Seq 结果一致，并进一步表明在蛋白质水平上缺乏 X 染色体的上调。总之，我们的研究结果否定了大野假说，需要对性染色体进化中目前的剂量补偿模型进行重大修订。
