Y chromosome is important for more than just sex and reproduction

New research has found that the Y chromosome can affect other cells in the body besides those related to reproduction.

University of Montreal professor Christian Deschepper, director of the Experimental Cardiovascular Biology research unit of the Montreal Clinical Research Institute, published the new findings in the research journal Scientific Reports in September. 

Both men and women have 23 chromosome pairs, including a pair of sex chromosomes. Women have two X chromosomes, while males have one X and one Y chromosome.

Previously scientists thought the genes on the Y chromosome were involved only in sexual reproduction, although these genes are also present in all of the body's cells.

To look at whether Y chromosome genes might have other functions, Deschepper inactivated two male genes on the Y chromosome of adult mice and observed how this changed the signaling pathways in cells.

Specifically, Deschepper focused on the effect of the deletion in cardiac-related cells. He compared the group of mice with inactivated male genes to a control group of mice. He examined RNA sequencing and chromatin (DNA and protein) profiles on the cardiac cells.

He hypothesized that the type of changes he found could explain why men and women react differently to certain diseases. For example, the virus that causes COVID-19 has twice the death rate in men than women.

Also, Deschepper's paper notes, the loss of the male Y chromosome in human blood cells that occurs with age is associated with "a host of disease manifestations, including shorter survival, increased cancer risk, cardiovascular events, Alzheimer disease and age-related macular degeneration."

In addition, Deschepper found that the mechanism was different from that of other genes. These  genes do not directly regulate cells but instead regulate their protein production.

The research looked at how the Uty regulatory gene on the Y chromosome affects surrounding male genes. The study also examined what the regulatory relationships are among the male-specific part of the Y chromosome (MSY). Another part of the research involved understanding the effects of Uty on the autosomal (non-sex) chromatin. The context for investigating the impact of Uty on adult heart transcriptome (RNA molecules). 

The paper notes that a defining feature of the MSY genes is a high level of co-expression, meaning that different genes simultaneously convert DNA information into a gene product like a protein. Such high levels of co-expression are rare, and the author speculates that this might have occurred because of evolutionary forces on the MSY that are different from those on other genes.

The fact that a high proportion of the co-expressed genes are non-coding may also be the result of evolutionary forces, the author notes.

The paper concludes that "MSY genes have demonstrable effects on regulators of adult somatic cell functions." But, the author notes, "such effects might result from MSY behaving as an entire integrated regulatory unit rather than from individually regulated MSY genes, and might involve mechanisms other than just transcriptional regulation of autosomal protein-coding genes."

In any case, the paper states, "These findings could constitute a stepping stone to better understand in which fashion chrY-related genetic differences may affect health-related outcomes."