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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Chromosomes, Mammalian / genetics
  • Dosage Compensation, Genetic*
  • Gene Expression Profiling
  • Genes, X-Linked
  • Humans
  • Mammals / genetics
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity / genetics
  • Sequence Analysis, RNA / methods*
  • X Chromosome / genetics*

Associated data

  • GEO/GSE12946
  • GEO/GSE13652
  • GEO/GSE3413