It sheds new light on a little-known role of Y chromosomal genes that are specific to men and could explain why men suffer differently from women from various diseases, including Covid-19.
The results were published this month in scientific reports by Christian Deschepper, professor at Université de Montréal, director of the research unit for experimental cardiovascular biology at the Montreal Clinical Research Institute.
“Our discovery provides a better understanding of how male genes on the Y chromosome enable male cells to function differently from female cells,” said Deschepper, lead author of the study who is also an associate professor at McGill University.
“In the future, these results could help shed some light on why some diseases appear differently in men and women.”
Genes that women lack
Humans each have 23 pairs of chromosomes, including one pair of sex chromosomes. While women have two X sex chromosomes, men have one X and one Y chromosome. This male chromosome carries genes that women lack. Although these male genes are expressed in all cells of the body, their only confirmed role to date has been essentially limited to the functions of the genital organs.
In his study, Deschepper performed a genetic manipulation that inactivated two male genes on the Y chromosome and changed several signaling pathways that play an important role in certain functions of non-sex organ cells. For example, under stress, some of the affected mechanisms could influence the way in which cells in the human heart defend themselves against aggressions such as ischemia (decreased blood supply) or mechanical stress.
In addition, the study showed that these male genes performed their regulatory functions in ways that were unusual when compared to the mechanisms generally used by most of the other genes on the non-sex chromosomes. Instead of specifically activating certain genes through direct action at the genome level, the Y chromosome appears to affect cell functions by affecting protein production.
The discovery of these functional differences could partly explain why the functions of male Y chromosome genes have so far been poorly understood, said Deschepper.
Men differ from women in the manifestation, severity and consequences of most diseases. A current example of this duality is Covid-19, the mortality rate of which is twice as high for men as for women.
CF Deschepper et al. (2020) Regulatory Effects of the Uty / Ddx3y Locus on Neighboring Chromosome Y Genes and Autosomal mRNA Transcripts in Non-Reproductive Cells of Adult Mice. Scientific reports. doi.org/10.1038/s41598-020-71447-3.