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.
Who are these “certain parts,” and to paraphrase what Stalin supposedly said about the Pope, “How any divisions do they have?
Vive la difference!
As a longtime student of developmental genetics, I’m not surprised by this. Since there is no demonstration that many or most of these differences have any physiological significance, this sort of descriptive science should be taken with a healthy dose of salt.
Urban Legend,
The better question is, how many HR departments do they have?
JackD,
Agreed. Of course, some people don’t like differences, not that there’s anything wrong with that.
Joel,
A couple of comments. First, the literature showing physiological differences between male and females is longstanding, even if it isn’t tied to the much newer genetic literature.
Second, I am assuming you mean SDE genes may not have physiological significance – otherwise you end up ruling out any physiological significance in having ovaries or testis resulting from sex specific genes rather than expression.
The authors of the study do specifically state this:
That is suggestive, not a demonstration, but they do make claims that are more than suggestive too. Before I get to them, one comment: you don’t need many or even most of SDE genes to have any physiological significance for there to be a huge physiological effect when a third of the genes are SDE.
So to begin:
In other words… the difference here seems to be SDE.
Supporting that, there’s also this:
Moving on, there’s this:
That puts musculature into the potential SDE category, if I read correctly.
And getting back to a point many, many times about why differences between population groups will keep coming up, in the end, it all ties in with alleviating diseases and harmful conditions:
Now, is there a slam dunk to from SDE to, say, thought processes? No. Is it possible this whole line of research will be debunked, like the benefits of power posing or some other some other drivel out of the field of psychology or X studies? Sure. On the other hand, is it more likely than not this will prove to be one more nail in the blank slate coffin?
So these “certain parts” are in HR departments. What outrages are they committing that requires these lessons from academic research intended for those trained in the field who can actually understand it?
As with so much of this stuff being posted lately on Angry Bear, what is the point? What problem are we supposed to address, and what is the remedy?
Of course there is something wrong with people who don’t agree with differences; they are bigots who wish the world to operate on principles different from what works. People who want things to be separated based on gender, race, religion, or national origin simply want power instead of what works for the mass of people.
They’ve been finding all sorts of things by studying differential gene expression. For example, nerve cells in muscles express genes associated with muscles while nerve cells in the spine and brain express a different set, quite unlike those of muscle based neurons. This, for example, might explain why nerves in muscles can reconnect while those in the spine cannot.
I’m not surprised that men and women have lots of genes that are expressed at different levels. If nothing else, women have babies, and that requires all sorts of modifications to anatomy, the immune system, the regulatory system and so on. Then there’s the menstrual cycle which involves a whole damned cascade of genes. Meanwhile men tend to be built differently and build muscle mass differently. Men tend to have hairier bodies and lose their cranial hair more readily than women. They also lack women’s subcutaneous fat layer. All those differences involve gene expression.
I wonder how different gene expression is among individuals, even individuals we might consider closely related. For example, how different is gene expression between identical twins raised in different economic milieus? The genome is a massive, redundant kludge. I’ll bet it has ten ways to do anything.
Nothing in your reply changes my post. Nobody–and I mean nobody–denies that humans are sexually dimorphic. And a finding of sexually dimorphic gene expression in a sexually dimorphic tissue like breast tissue is like finding water at the bottom of the ocean.
“On the other hand, is it more likely than not this will prove to be one more nail in the blank slate coffin?”
In any meaningful sense, no. You don’t need gene expression profiling to tell that humans are sexually dimorphic. Nobody is claiming that sexual dimorphism in humans, including susceptibility to diseases such as osteoporosis, ovarian cancer, Alzheimers, testicular cancer, etc, is a social construct.
“For example, how different is gene expression between identical twins raised in different economic milieus?”
Patterns of gene expression between monozygotic gene pairs diverge with age. How much is a breakdown in regulation vs. difference in post-partum environment isn’t clear.
http://www.pnas.org/content/102/30/10604.full.pdf
Joel,
Careful. Your lack of surprise should travel very easily into a lack of surprise over papers like this, or this or this.
I’ve worked at a medical school for over 30 years. This sort of sloppy use of “race” doesn’t surprise me, nor does the sloppy editing of biomedical research journals. In these cases, the authors are using “race” as a synonym for “ancestry.”
Exactly. That’s the point I kept making on another thread.
Ah, then we agree: “race” in humans is a social construct and not a meaningful taxonomic term.
Ancestry, of course, is the foundation of genetics. It is also at the core of environmental factors like nutrition, education, religion, language.
So why, then, do you keep linking to articles that use “race?” What, exactly, is your point?