The X to Autosome Expression Ratio in Haploid and Diploid Human Embryonic Stem Cells

Ohno proposed that the expression levels of X-linked genes have been doubled to compensate the degeneration of Y-linked homologs during the evolution of mammalian sex chromosomes, but RNA sequencing in human somatic tissues showed no such upregulation for the vast majority of X-linked genes. Here we report that the X to autosome expression ratio equals ∼1 in haploid human parthenogenetic embryonic stem (pES) cells and ∼0.5 in diploidized pES cells, both with one active X chromosome. Although we confirmed the upregulation of ∼5% of X-linked genes encoding members of large protein complexes in diploids, these genes are also upregulated in haploids, breaking the otherwise balanced dosage. These findings argue against Ohno's hypothesis for both haploid and diploid cells and demonstrate that, at least in humans, precise gene regulation for dosage balance, even for members of large protein complexes, is much less critical than is commonly thought.