Study sheds new light on the role of Y chromosome genes

Scientists have a shed new light on a little-known role of Y chromosome genes, which are specific to men, and may help explain why men suffer differently than women from numerous diseases, including COVID-19.

Study sheds new light on the role of Y chromosome genes
In his study, Deschepper performed a genetic manipulation that inactivated two male genes on the Y chromosome, altering several signaling pathways that play important roles in certain functions of non-sex organ cells. Image Credit: GETTY.

The results of the study were recently published in the Scientific Reports journal by Christian Deschepper, the University of Montreal professor and director of the Experimental Cardiovascular Biology research unit of the Montreal Clinical Research Institute.

Our discovery provides a better understanding of how male genes on the Y chromosome allow male cells to function differently from female cells. In the future, these results could help to shed some light on why some diseases occur differently in men and women.”

Christian Deschepper, Study Lead Author and Associate Professor, McGill University

Genes that females lack

Every human has 23 pairs of chromosomes, inclusive of a pair of sex chromosomes. Females carry a pair of X sex chromosomes, while males carry one X and one Y chromosome. Genes that are absent in women are carried by the male chromosome. Even though these male genes are expressed in every cell of the body, their only proven role to date has been fundamentally restricted to the functions of the sex organs.

During his study, Deschepper conducted out a genetic manipulation that deactivated a pair of male genes located on the Y chromosome, modifying many signaling pathways that play a crucial role in specific functions of non-sex organ cells.

For instance, under stress, certain affected mechanisms could affect the way through which cells located in human hearts protect themselves against aggressions, like mechanical stress or ischemia (reduced blood supply).

The research also revealed that such male genes carried out their regulatory functions in a manner that was strange compared to the mechanisms often used by a majority of other genes located on the non-sex chromosomes. Therefore, instead of particularly simulating certain genes through direct action at the genomic level, the Y chromosome appears to impact cellular functions by acting on protein synthesis.

According to Deschepper, the discovery of these functional differences may partly explain why the functions of male Y chromosome genes studied have not been clearly understood, to date.

Men are different from women in terms of the severity, manifestation, and consequences of a majority of the diseases. A new example of this duality is COVID-19, which has double the mortality rate in men than in women.

Source:
Journal reference:

Deschepper, C. F (2020) Regulatory effects of the Uty/Ddx3y locus on neighboring chromosome Y genes and autosomal mRNA transcripts in adult mouse non-reproductive cells. Scientific Reports. doi.org/10.1038/s41598-020-71447-3.

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