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Different but Equal?

Here’s a fascinating recent article with the forbidding title of The landscape of sex-differential transcriptome and its consequent selection in human adults.  I’ll provide the abstract, and then a translation into English.  Here’s the abstract:

Background
The prevalence of several human morbid phenotypes is sometimes much higher than intuitively expected. This can directly arise from the presence of two sexes, male and female, in one species. Men and women have almost identical genomes but are distinctly dimorphic, with dissimilar disease susceptibilities. Sexually dimorphic traits mainly result from differential expression of genes present in both sexes. Such genes can be subject to different, and even opposing, selection constraints in the two sexes. This can impact human evolution by differential selection on mutations with dissimilar effects on the two sexes.

Results
We comprehensively mapped human sex-differential genetic architecture across 53 tissues. Analyzing available RNA-sequencing data from 544 adults revealed thousands of genes differentially expressed in the reproductive tracts and tissues common to both sexes. Sex-differential genes are related to various biological systems, and suggest new insights into the pathophysiology of diverse human diseases. We also identified a significant association between sex-specific gene transcription and reduced selection efficiency and accumulation of deleterious mutations, which might affect the prevalence of different traits and diseases. Interestingly, many of the sex-specific genes that also undergo reduced selection efficiency are essential for successful reproduction in men or women. This seeming paradox might partially explain the high incidence of human infertility.

Conclusions
This work provides a comprehensive overview of the sex-differential transcriptome and its importance to human evolution and human physiology in health and in disease.

The article was interesting, but a slog given my lack of knowledge of the field.  I don’t mind admitting I couldn’t follow it in its entirety, though  I did manage to acquire a feeling of inadequacy and the start of a headache. So for a translation, I will rely on distinguished geneticist Jenny Graves who just wrote a piece about the article that is quite accessible and from which I will quote below. Graves starts with the punchline:

Most of us are familiar with the genetic differences between men and women.

Men have X and Y sex chromosomes, and women have two X chromosomes. We know that genes on these chromosomes may act differently in men and women.

But a recent paper claims that beyond just genes on X and Y, a full third of our genome is behaving very differently in men and women.

These new data pose challenges for science, medicine and maybe even gender equity.

Here’s a more extensive summary:

In their new paper, the authors Gershoni and Pietrokovsk looked at how active the same genes are in men and women. They measured the RNA produced by 18,670 genes in 53 different tissues (45 common to both sexes) in 544 adult post mortem donors (357 men and 187 women).

They found that about one third of these genes (more than 6,500) had very different activities in men and women. Some genes were active in men only or women only. Many genes were far more active in one sex or the other.

A few of these genes showed sex biased activity in every tissue of the body. More commonly, the difference was seen in one or a few tissues.

Most of these genes were not on sex chromosomes: only a few lay on the Y or the X.

How could a third of our genes be differently controlled in men and women?

We now understand that proteins work in extensive networks. Change the amount of one protein produced by one gene, and you change the amounts of all the proteins produced by many genes in a long chain of command.

We also know that hormones have powerful influences on gene activity. For instance, testosterone and estrogen dial up or down many genes in reproductive and body tissues.

Here is how Graves’ piece ends:

What do these new insights mean for our progress toward gender equity? A bad outcome could be appeals to return to outdated sexual stereotypes. A good outcome will be recognition of sex differences in medicine and treatment.

I think what Graves is after can be characterized as “different but equal.” And though it makes perfect sense given the current state of genetics and biology (to say nothing of common sense), such a philosophy would be quite unwelcome in certain parts these days.

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