Quantitative analysis of Y-Chromosome gene expression across 36 human tissues
- Alexander K. Godfrey1,2,
- Sahin Naqvi1,2,
- Lukáš Chmátal1,
- Joel M. Chick3,
- Richard N. Mitchell4,
- Steven P. Gygi3,
- Helen Skaletsky1,5 and
- David C. Page1,2,5
- 1Whitehead Institute, Cambridge, Massachusetts 02142, USA;
- 2Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA;
- 3Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 4Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 5Howard Hughes Medical Institute, Whitehead Institute, Cambridge, Massachusetts 02142, USA
Abstract
Little is known about how human Y-Chromosome gene expression directly contributes to differences between XX (female) and XY (male) individuals in nonreproductive tissues. Here, we analyzed quantitative profiles of Y-Chromosome gene expression across 36 human tissues from hundreds of individuals. Although it is often said that Y-Chromosome genes are lowly expressed outside the testis, we report many instances of elevated Y-Chromosome gene expression in a nonreproductive tissue. A notable example is EIF1AY, which encodes eukaryotic translation initiation factor 1A Y-linked, together with its X-linked homolog EIF1AX. Evolutionary loss of a Y-linked microRNA target site enabled up-regulation of EIF1AY, but not of EIF1AX, in the heart. Consequently, this essential translation initiation factor is nearly twice as abundant in male as in female heart tissue at the protein level. Divergence between the X and Y Chromosomes in regulatory sequence can therefore lead to tissue-specific Y-Chromosome-driven sex biases in expression of critical, dosage-sensitive regulatory genes.
Footnotes
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.261248.120.
- Received January 21, 2020.
- Accepted May 18, 2020.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
