RNA sequencing shows no dosage compensation of the active X-chromosome
RNA sequencing shows no dosage compensation of the active X-chromosome
复制标题
RNA测序显示活性X染色体没有剂量补偿
DOI：
10.1038/ng.711
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发表时间：
2010-12-01
期刊：
影响因子：
30.8
通讯作者：
He, Xionglei
中科院分区：
文献类型：
--
作者：
Xiong, Yuanyan;Chen, Xiaoshu;He, Xionglei
哺乳动物的两性细胞通常都含有一条活跃的X染色体，但有两组常染色体。以前的假设是，X连锁基因的表达水平是每个活跃等位基因常染色体基因水平的两倍，以平衡X染色体和常染色体之间的基因剂量(称为Ohno假说)。基于微阵列的基因表达水平在一个X染色体和两个常染色体(X与两个常染色体的比率(X：AA)∼1)之间无法区分的观察结果支持了这一假说。在这里，我们显示核糖核酸测序比微阵列更敏感，且核糖核酸序列数据显示在人和小鼠中X：AA比率为∼0.5。在秀丽隐杆线虫中，X：AA比值从幼虫的∼1递减到成虫的∼0.5。蛋白质组学数据与RNA-Seq结果一致，进一步表明在蛋白质水平上缺乏X上调。总之，我们的发现否定了Ohno的假设，需要对目前的性染色体进化中的剂量补偿模型进行重大修改。
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. InCaenorhabditis eleganshermaphrodites, 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.