SEX CHROMOSOMES INFLUENCE ON AUTOSOMAL GENE EXPRESSION

The ancestral pair of autosomes split into the X and Y chromosomes. In addition to developing distinct roles like identifying sex and influencing sex differences in males and females—X and Y also continue to perform shared roles that are inherited from their common ancestor. Recent studies have demonstrated that the expression of genes on the X and Y chromosomes affects cells not only in the reproductive system but also in other parts of the body by regulating the expression of thousands of genes located on different chromosomes.The X and Y chromosomes, respectively, include the gene pair ZFX and ZFY, which together account for almost half of this regulatory behavior. The researchers discovered that these genes essentially had the identical regulatory effects on one another. Given how important this regulatory function is to human growth and development, it is possible that ZFX and ZFY independently preserved the important gene regulatory role that they inherited from their common ancestor, even after their individual chromosomes separated. The genes governed by ZFX and ZFY are implicated in numerous significant biological processes, indicating that the sex chromosomes play a significant role in functions that extend beyond those associated with sexual traits.

The researchers measured how gene expression changed in each cell type with each additional X or Y. They focused on two cell types that they selected for ease of sample acquisition: skin-cell derived fibroblasts, which help form our connective tissues, and lymphoblastoid cells, a type of immune cell.

    A karyotype of the complete set of human chromosomes.

They discovered that variations in the quantity of X and/or Y chromosomes present caused thousands of genes to alter in expression. Gene expression was altered by an equal amount with each extra X or Y chromosome due to the effects' linear scaling. The genes impacted and the degree of the effects varied depending on the type of cell, indicating that every kind of cell in the body might react differently to the regulation of genes by X and Y chromosome genes.The effect of an extra X tended to resemble the effect of an extra Y for a given gene in a particular cell type.

There are two types of X chromosomes, and only one of them differentiates between typical males and females, despite the fact that the human sex chromosomes are designated as X and Y. There is one "active X" chromosome in each and every human being. This chromosome has no effect on sex because, like autosomes, it is uniformly present.Typical males have the Y chromosome, whereas typical females have the "inactive X" chromosome, which is genetically identical to the active X but has most of its genes switched off. This is what separates normal males and females from each other. Any more X chromosomes in individuals with abnormal sex chromosomal compositions will always be inactive X chromosomes; therefore, when the researchers examined the impact of adding more X chromosomes, they were really examining the impact of adding more inactive X chromosomes. The X and Y are not the sex chromosomes that the researchers discovered to be influencing widespread gene expression; rather, it is the inactive X and Y. The inactive X and the Y both control the expression of several genes on the active X chromosome.In conclusion, the Y and inactive X chromosomes work as gene regulators and sex chromosomes, respectively, whereas the active X chromosome functions like an autosome.

REFERENCE:

“The human Y and inactive X chromosomes similarly modulate autosomal gene expression” by Adrianna K. San Roman, Helen Skaletsky, Alexander K. Godfrey, Neha V. Bokil, Levi Teitz, Isani Singh, Laura V. Blanton, Daniel W. Bellott, Tatyana Pyntikova, Julian Lange, Natalia Koutseva, Jennifer F. Hughes, Laura Brown, Sidaly Phou, Ashley Buscetta, Paul Kruszka, Nicole Banks, Amalia Dutra, Evgenia Pak, Patricia C. Lasutschinkow and David C. Page, 13 December 2023, Cell Genomics.
DOI: 10.1016/j.xgen.2023.100462