No X-chromosome dosage compensation in human proteomes

Abstract

The X and Y chromosomes of placental and marsupial mammals originated from a pair of autosomes. Ohno proposed that the expression levels of X-linked genes must have been doubled in males to compensate for the degeneration of their Y homologs. Recent mRNA sequencing experiments, however, found at most weak or infrequent X-chromosome dosage compensation. Nonetheless, dosage compensation need not occur at the mRNA level, because ultimately it is the protein concentration that matters. Analyzing human proteomic data from 22 tissues, we here report that X upregulation is absent at the protein level, indicating that Ohno's hypothesis is also invalid at the protein level.

Keywords: Ohno’s hypothesis; protein expression; proteomics; sex chromosome evolution.

Fig. 1.

No X-chromosome dosage compensation in human proteomes. (a) Fractions of X-linked (circles) and autosomal (triangles) genes with proteomic data. For each tissue, the symbols are closed when the fractions are significantly different between the X and autosomes (P < 0.05, χ² test) and are otherwise open. The mean fractions among either 17 nonsex-specific tissues or all 22 tissues are compared between the X and autosomes with a two-tailed paired t-test (closed, P < 0.05; open, P ≥ 0.05). The tissue name is in blue when the tissue samples are from males, in red when they are from females, and in black when they are from both sexes. (b) X:AA ratio in median protein concentration. For each tissue, the error bar shows the 95% confidence interval derived from 1,000 bootstrap replications, and a two-tailed Mann–Whitney U test is used to test the equality between the protein concentrations of X-linked and autosomal genes (closed, P < 0.05; open, P ≥ 0.05). The error bar of a mean ratio across tissues shows the 95% confidence interval of the mean derived from 1,000 bootstraps of the X:AA ratios of the individual tissues involved, and a two-tailed t-test is used to compare the mean X:AA ratio with 1 (closed, P < 0.05; open, P ≥ 0.05). (c) X:AA ratio in median mRNA concentration for the genes used in the proteomic analysis. All symbols and tests are the same as in panel b. (d) X:AA ratio in median value of protein concentration relative to mRNA concentration. All symbols and tests are the same as in panel b.