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Developmental Biology - Y Chromosome Acts on Proteins

Y Chromosome Activates Proteins - Not Genes

Male genes perform regulatory functions differently than most genes - which might explain why men and women experience diseases differently...

The findings are published this month in Scientific Reports by Université de Montréal professor Christian Deschepper, Director, Experimental Cardiovascular Biology Research, 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 shed light on why some diseases occur differently in men and women."
Christian F. Deschepper PhD, Associate Professor, McGill University, Montreal, Canada, and study's lead author.

Females Genes vs Male Genes

Humans each have 23 pairs of chromosomes, including one pair of sex chromosomes. While females carry two X chromosomes, males carry one X and one Y. This one male chromosome carries genes that females don't. Although male genes are expressed [functioning] in all cells of the body, to date their only confirmed role is the function of male sex organs.
Deschepper's experiment inactivated two male genes on the Y chromosome, thus altering several cell signal paths important in the function of all other non-sex organ cells.

Under stress, for example, some affected cell functions could influence how human heart cells defend themselves against ischemia (reduced blood supply) or other mechanical stresses.

His study revealed that the male gene performed unusual regulatory functions when compared to non-sex chromosomes. Instead of directly activating specific genes, the Y chromosome seems to affect only the activation of protein production - the small molecules produced by genes.

Stanford University - The Tech Interactive

A gene is a stretch of DNA on a chromosome with instructions for making a protein. Each chromosome has many genes with humans having over 22,000 genes.

A protein is a molecular machine doing a specific job. Some proteins (amylase) help us digest food. Others (opsins) help us see colors. And still others (hemoglobins) help our blood take oxygen to and carbon dioxide away from our cells.

This discovery may explain why the functions of male Y chromosome genes have long been misunderstood, suggests Deschepper.
Males differ from females in manifestation, severity and consequence, of most diseases. A recent example of this duality is Covid-19, with a mortality rate twice as high in men than in women.

In addition to sperm-related genes, the male-specific chromosome Y (chrY) contains a class of ubiquitously expressed and evolutionary conserved dosage-sensitive regulator genes that include the neighboring Uty, Ddx3y and (in mice) Eif2s3y genes. However, no study to date has investigated the functional impact of targeted mutations of any of these genes within adult non-reproductive somatic cells. We thus compared adult male mice carrying a gene trap within their Uty gene (UtyGT) to their wild-type (WT) isogenic controls, and performed deep sequencing of RNA and genome-wide profiling of chromatin features in extracts from either cardiac tissue, cardiomyocyte-specific nuclei or purified cardiomyocytes. The apparent impact of UtyGT on gene transcription concentrated mostly on chrY genes surrounding the locus of insertion, i.e. Uty, Ddx3y, long non-coding RNAs (lncRNAs) contained within their introns and Eif2s3y, in addition to possible effects on the autosomal Malat1 lncRNA. Notwithstanding, UtyGT also caused coordinate changes in the abundance of hundreds of mRNA transcripts related to coherent cell functions, including RNA processing and translation. The results altogether indicated that tightly co-regulated chrY genes had nonetheless more widespread effects on the autosomal transcriptome in adult somatic cells, most likely due to mechanisms other than just transcriptional regulation of corresponding protein-coding genes.

Christian F. Deschepper.

The work was partly funded by Grant MOP-93583 from the Canadian Institutes for Health Research (CIHR). I am deeply grateful for the help of the IRCM Bioinformatics, Molecular Biology, Cytofluorometry and Animal Physiology Core Laboratories, and acknowledge in particular the contributions of Virginie Calderon, Caroline Grou, Odile Neyret, Myriam Rondeau, Éric Massicotte, Julie Lord and Manon Laprise. I also thank Sylvie Picard for technical help, Mariana Bego and Mélanie Laporte for help with generation of lentiviral particles, and Pierre Bensidoun for immunocytochemistry and microscopy. I thank J. Eales and M. Tomaszewski for sharing data pertaining to one of their previous publication.

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Sep 28 2020   Fetal Timeline   Maternal Timeline   News

By inactivating two male genes on the Y chromosome of male mice - researchers found only protein development was affected and not gene function. Genes control the making of proteins. This unexpected result may explain why men have twice the mortality of women under Covid-19 and in many other major diseases.

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