Genome complexity: x and y control more than sex (Introduction)

by David Turell , Saturday, December 16, 2023, 16:54 (133 days ago) @ David Turell

Widespread controls:

https://phys.org/news/2023-12-sex-chromosomes-responsible.html

"Human sex chromosomes originated from a pair of autosomes, the ordinary or non-sex chromosomes that contain the majority of our genome and come in identical pairs. That ancestral pair of autosomes diverged to become two different chromosomes, X and Y. Even though X and Y have grown apart from each other and taken on unique functions—namely, determining sex and driving sex differences in males and females—they also retain shared functions inherited from their common ancestor.

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"The research, published in Cell Genomics on December 13, shows that genes expressed from the X and Y chromosomes impact cells throughout the body—not just in the reproductive system—by dialing up or down the expression of thousands of genes found on other chromosomes.

"Furthermore, the researchers found that the gene pair responsible for around half of this regulatory behavior, ZFX and ZFY, found on the X and Y chromosome respectively, have essentially the same regulatory effects as each other. This suggests that ZFX and ZFY inherited their role as influential gene regulators from their shared ancestor and have independently maintained it, even as their respective chromosomes diverged, because that regulatory role is critical for human growth and development. The genes regulated by ZFX and ZFY are involved in all sorts of important biological processes, showing that the sex chromosomes contribute widely to functions beyond those related to sex characteristics.

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"'By using the natural variation of sex chromosome composition in the human population, we were able to mathematically model how the number of X and Y chromosomes impacts expression of genes in a way that's never been done before. By taking this approach, we gained new insights into the massive impact that X and Y genes have broadly throughout the genome," San Roman says.

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"They found that thousands of genes changed their expression levels in response to changes in the number of X and/or Y chromosomes present. The effects scaled linearly, meaning that each additional X or Y chromosome changed gene expression by the same amount. Which genes were affected, and by how much, were different for each of the cell types, suggesting that each type of cell in the body may have a unique response to gene regulation by X and Y chromosome genes.

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"A subtlety thus far not discussed is that when Page and San Roman think about the sex chromosomes, they no longer think of X as most people think of it. Their work has convinced them that our current understanding of the sex chromosomes is imprecise. Although the human sex chromosomes are defined as X and Y, in fact there are two types of X chromosomes, and only one of them differs between typical males and females. Every human in the world has one "active X" chromosome. This chromosome is, like an autosome, universally present and so its presence has no bearing on sex.

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"'These chromosomes have historically been known as the 'inactive' X and the 'gene-poor' Y chromosomes, and given little attention beyond how they contribute to sex differentiation, so it was stunning to us to see how wide their network of influence was," Page says. "These chromosomes contain genes like ZFX and ZFY that are global gene regulators, and I think as we learn more about them, it's going to completely change how we think about the genetics of the human X and Y chromosomes.'"

Comment: it is always surprising to me that researchers are so surprised at the complexity they unearth. We don't know what we don't know, and genetic controls are purposeful and precise.