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No X-chromosome dosage compensation in human proteomes

Xiaoshu Chen¹, Jianzhi Zhang²

¹Department of Ecology and Evolutionary Biology, University of Michigan.

Molecular Biology and Evolution

|February 21, 2015

Summary

Ohno's hypothesis proposed X-linked gene expression doubling in males to balance sex chromosomes. However, this study found no evidence of X-chromosome upregulation at the protein level in humans, invalidating the hypothesis.

Area of Science:

Genetics
Mammalian Evolution
Proteomics

Background:

The X and Y chromosomes in mammals evolved from autosomes.
Ohno's hypothesis posits that males double X-linked gene expression to compensate for Y chromosome degeneration.
Previous mRNA studies showed limited evidence for X-chromosome dosage compensation.

Purpose of the Study:

To investigate whether X-chromosome dosage compensation occurs at the protein level.
To test the validity of Ohno's hypothesis in human tissues.

Main Methods:

Analysis of human proteomic data from 22 distinct tissues.
Quantitative assessment of protein expression levels from X-linked genes.

Main Results:

No significant upregulation of X-linked genes was detected at the protein level across human tissues.
Findings contradict the expectation of dosage compensation based on Ohno's hypothesis.

Conclusions:

Ohno's hypothesis regarding X-chromosome dosage compensation is not supported at the protein level in humans.
Protein levels do not exhibit the compensatory upregulation predicted for X-linked genes.

Keywords:

Ohno’s hypothesis protein expression proteomics sex chromosome evolution

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Dosage Compensation

Dosage Compensation

In animals, gender is determined by the number and type of sex chromosome. For example, human females have two X chromosomes, and males have one X and one Y chromosome, whereas C.elegans with one X chromosome is a male, and the one with two X chromosomes is a hermaphrodite.
In addition to sexual development, the X chromosome has genes involved in autosomal functions such as brain development and the immune system. Therefore, males and females with distinct numbers of X chromosomes will...

X and Y Chromosomes

X and Y Chromosomes

Among mammals, the gender of an organism is determined by the sex chromosomes. Humans have two sex chromosomes, X and Y. Every human diploid cell has 22 pairs of autosomes and one pair of sex chromosomes. A human female has two X chromosomes, while a male has one X chromosome and one Y chromosome.
The germline cells such as egg and sperm cells carry only half the number of chromosomes, i.e., 22 autosomes and one sex chromosome. All eggs have an X chromosome, while sperm cells can carry an X or...

The Ratio of X Chromosome to Autosomes

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In most organisms, sex is determined by the ratio of X and Y chromosomes. However, in some organisms, such as Drosophila and C.elegans, sex is determined by the ratio of the number of X chromosomes to the number of sets of autosomes. The Y chromosome in Drosophila is active but does not determine sex. It contains genes responsible for the production of sperms in adult flies.
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X-Inactivation

X-Inactivation

The human X chromosome contains over ten times the number of genes as in the Y chromosome. Since males have only one X chromosome, and females have two, one might expect females to produce twice as many of the proteins, with undesirable results.

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