title: 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.
authors.affiliation: State Key Laboratory of Biocontrol, College of Life Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yuanyan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Chen
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Chen
authors.forename: Xunzhang
authors.initials: X
authors.lastname: Wang
authors.forename: Suhua
authors.initials: S
authors.lastname: Shi
authors.forename: Xueqin
authors.initials: X
authors.lastname: Wang
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhang
authors.forename: Xionglei
authors.initials: X
authors.lastname: He
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D033481:Chromosomes, Mammalian / Q000235:genetics; D004303:Dosage Compensation, Genetic; D020869:Gene Expression Profiling; D050172:Genes, X-Linked; D006801:Humans; D008322:Mammals / Q000235:genetics; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics; D017423:Sequence Analysis, RNA / Q000379:methods*; D014960:X Chromosome / Q000235:genetics*