Researchers identify 6,500 genes that are expressed differently in men and women

Researchers identify 6,500 genes that are expressed differently in men and women
6500 genes are expressed differently in men and women. Credit: Weizmann Institute of Science

Men and women differ in obvious and less obvious ways—for example, in the prevalence of certain diseases or reactions to drugs. How are these connected to one's sex? Weizmann Institute of Science researchers recently uncovered thousands of human genes that are expressed—copied out to make proteins—differently in the two sexes. Their findings showed that harmful mutations in these particular genes tend to accumulate in the population in relatively high frequencies, and the study explains why. The detailed map of these genes, reported in BMC Biology, provides evidence that males and females undergo a sort of separate, but interconnected evolution.

Several years ago, Prof. Shmuel Pietrokovski and Dr. Moran Gershoni of the Weizmann Institute's Molecular Genetics Department asked why the prevalence of certain human diseases is common. Specifically, about 15% of couples trying to conceive are defined as infertile, which suggested that mutations that impair fertility are relatively widespread. This seems paradoxical: Common sense says that these mutations, which directly affect the survival of the species by reducing the number of offspring, should have been quickly weeded out by natural selection. Pietrokovski and Gershoni showed that mutations in genes specific to sperm formation persist precisely because the genes are expressed only in men. A mutation that is problematic for only half the population, no matter how detrimental, is freely passed on to the next generation by the other half.

In the present study, the researchers expanded their analyses to include genes that, though not necessary for fertility, are still expressed differently in the two sexes. To identify these genes, the scientists turned to the GTEx project—a very large study of human recorded for numerous organs and tissues in the bodies of close to 550 adult donors. That project enabled, for the first time, the comprehensive mapping of the human sex-differential genetic architecture.

Pietrokovski and Gershoni looked closely at around 20,000 protein-coding genes, sorting them by sex and searching for differences in expression in each tissue. They eventually identified around 6,500 genes with activity that was biased toward one sex or the other in at least one tissue. For example, they found genes that were highly expressed in the skin of men relative to that in 's skin, and they realized that these were related to the growth of body hair. Gene expression for muscle building was higher in men; that for fat storage was higher in women.

Yet another difference

The two then looked at tendencies to accumulate mutations, to see if natural selection puts more or less pressure on genes that are specific to men or women. That is, to what extent are weeded out or tolerated in the population? Indeed, the researchers found that the efficiency of selection is weaker in many such genes. "The more a gene was specific to one sex, the less selection we saw on the gene. And one more difference: This selection was even weaker with men," says Gershoni. Although they do not have a complete explanation for this additional difference, the researchers point to a theory of sexual evolution first proposed in the 1930s: "In many species, females can produce only a limited number of offspring while males can, theoretically, father many more; so the species' survival will depend on more viable females in the population than males," explains Pietrokovski. "Thus can be more 'lax' with the genes that are only harmful to males."

Aside from the sexual organs, the researchers discovered quite a few sex-linked genes in the mammary glands—not so surprising, except that about half of these genes were expressed in men. Because men have fully fitted but basically nonfunctional mammary equipment, the scientists made an educated guess that some of these genes might suppress lactation.

Less obvious locations included genes that were found to be expressed only in the left ventricle of the heart in women. One of these genes, which is also related to calcium uptake, showed very high expression levels in younger women that sharply decreased with age; the scientists think that they are active in women up to menopause, protecting their hearts, but leading to heart disease and osteoporosis in later years when the gene expression is shut down. Yet another gene that was mainly expressed in women was active in the brain, and though its exact function is unknown, the scientists think it may protect the neurons from Parkinson's—a disease that has a higher prevalence and earlier onset in men. The researchers also identified gene expression in the liver in women that regulates drug metabolism, providing molecular evidence for the known difference in drug processing between women and men.

"The basic genome is nearly the same in all of us, but it is utilized differently across the body and among individuals," says Gershoni. "Thus, when it comes to the differences between the sexes, we see that evolution often works on the level of gene expression." Pietrokovski adds: "Paradoxically, sex-linked genes are those in which harmful mutations are more likely to be passed down, including those that impair fertility. From this vantage point, men and women undergo different selection pressures and, at least to some extent, human evolution should be viewed as co-evolution. But the study also emphasizes the need for a better understanding of the differences between men and women in the that cause disease or respond to treatments."

Prof. Shmuel Pietrokovski's research is supported by the Leo and Julia Forchheimer Center for Molecular Genetics; and the estate of Georges Lustgarten. Prof. Shmuel Pietrovski is the incumbent of the Herman and Lilly Schilling Foundation Professorial Chair.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to scientists, students, technicians and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials and developing new strategies for protecting the environment.

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Mutations from Mars: Researchers explain why genetic fertility problems can persist in a population

More information: Moran Gershoni et al. The landscape of sex-differential transcriptome and its consequent selection in human adults, BMC Biology (2017). DOI: 10.1186/s12915-017-0352-z
Journal information: BMC Biology

Citation: Researchers identify 6,500 genes that are expressed differently in men and women (2017, May 4) retrieved 16 October 2019 from
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May 04, 2017
Wait a minute, I thought one could simply choose a gender that may not be what was "arbitrarily" assigned at birth. Has anyone informed those marchers for Science about this?

Thank you for the laugh.
I don't think there is a single person on Tumblr who knows anything about science, since it would shatter their flawed world view and make them realize that their tendency to want to be another gender is merely a mental illness.

May 04, 2017
This is a grave day for science, it just lost a bunch of hipsters...

May 05, 2017
You two are confusing gender with the sex organs people are born with. Gender is a human construct, the sex organs are not. In our society we identify each other based on external (and internal) parts that those who feel are not the gender they were born with feel they must alter to fit into the gender identity they are comfortable with and that we all use.

Im guessing you both think homosexuality is also a mental illness...

May 05, 2017
Im guessing you both think homosexuality is also a mental illness
And I'm thinking you think it's a choice or a spiritual grant if some sort rather than biological, meaning genetic.

For that to be true there must be an evolutionary advantage to it that's not readily apparent. But let me offer a possibility.

Humans are a domesticated species. We have been artificially selected over 1000s of genes for our affinity for tribal life.

Living peacefully in tribes requires us to forego many behaviors that would otherwise be considered normal in the wild.

Apes became human through the use of their technology. Tech enabled them to systematically eliminate elements in their environment which were keeping their numbers in check.

This resulted in chronic overpopulation. It led to overgrowth and inevitable inter- and intra-conflict.

May 05, 2017
Many species have biological ways of limiting growth. Rabbit females in overcrowded warrens for instance will absorb unborn fetuses in the womb.

Homosexuals within the tribe could still work to support and defend it while not contributing to the burden of overpopulation. Homosexuality can be the expected result of group selection. It could be the epigenetic response of a mother's perception of overcrowding within the tribe, to effectively neuter her children in the womb. And yet these people could still procreate if the tribe needed to recover from disaster.

There is a higher incidence of younger brothers being homosexual. Could this be a mother's epigenetic desire to limit competition for her firstborn in a crowded tribe? Are more homosexuals born in urban settings? Are there fewer born after wars and pandemics?

There is NOTHING about the human animal that is not entirely biological. Metaphysics is a survival strategy for maintaining a space at the campfire.

May 05, 2017
"Lot Leaves Sodom
19 The two angels came to Sodom in the evening as Lot was sitting near the city gate. When he saw them, he got up and went to them and bowed facedown on the ground. 2 Lot said, "Sirs, please come to my house and spend the night. There you can wash your feet, and then tomorrow you may continue your journey."

The angels answered, "No, we will spend the night in the city's public square."

3 But Lot begged them to come, so they agreed and went to his house. Then Lot prepared a meal for them. He baked bread without yeast, and they ate it.

4 Before bedtime, men both young and old and from every part of Sodom surrounded Lot's house. 5 They called to Lot, "Where are the two men who came to you tonight? Bring them out to us so we can have sexual relations with them."

6 Lot went outside to them, closing the door behind him. 7 He said, "No, my brothers! Do not do this evil thing."

-Religionists hate anything that restricts flock growth.

May 05, 2017
On the contrary, homosexuality is a lifestyle choice (and a poor one, in my opinion) that diverts the normal use of a man's anus from digestive system waste removal to... you know what. Hardly should be considered normal, even less so celebrated
Choice? What about those of us to whom the thought is genuinely revolting? Are you saying that homosexuals are a subset of weak ambivalent people who succumb to the temptation of natural urges that are present in all of us?

Because I can assure you that theyre not. And if from your perspective they are, then perhaps youre genetically predisposed to expending your urges in non-procreative ways. For the good of the tribe that is.

Heres a clue: every kind of sex is intrinsically revolting to a significant portion of the populace. Which means that the revulsion is as normal as the proclivity.

Although I find it puzzling that I am extremely attracted to Kate McKinnon. No not the clinton character shudder

May 05, 2017
I am not implying anything abut homosexuals being a weak subset of people, merely stating my opinion that they are so of their own choosing, many having been victims as children
-And Im saying that too much of our behavior is used for sociopolitical purposes. Merely explaining homosexuality in a biological way will not convince the majority of heteros who are revulsed by the behavior to acceept it.

Like the typical human your dog cares not why you dont want him to pee on the rug. He responds best to fear and shaming.

Thats the major purpose of modern religion isnt it? To frighten and shame us into resisting our natural impulses yes?

A homosexual can no more change their orientation than a hetero can. They can only pretend, as the overwhelming majority of gays in iran are forced to do.

This means that it is entirely biological. Evolutionary. And so there must be a purpose for it which benefits the tribe.

And I gave you an entirely plausible one.

May 05, 2017
You listen to kate talking about her gaydom and you can begin to understand how natural it is for her.

-In earlier gens she would have been considered the quintessential frigid wife.

I think shes cool as hell.
No, that doesn't make me (us?) homophobic, as much as intolerant activists sling that word around. Disagreeing with someone's lifestyle and opting not to celebrate their unnatural use of their bodies is not homophobic
Youre not being honest with yourself. Youre the dog who has been taught to accept the cat in the house.

May 06, 2017
and will ignore further ones due to your abject lack of common decency and respect
Are you trying to shame me? Of course you are.
Animals that are trainable, such as dogs, respond best to praise and reward not punishment
-So by extension we should abolish the penal system?

Throughout all of human development negative reinforcement has gotten us to where we are. All animals of every species teach their young using punishment, regardless of what Walt Disney told you.

The new age discrediting of it doesnt seem to be working very well for the majority of people.
a man cannot change his gender simply by identifying as a woman
-No, genes determine which gender we identify as.
I would hope you not ignore the streak of mental illness in such a person
-So youre calling gaydom a mental illness and declaring it science?

Onanism used to be an unmistakable symptom as well. Your notions of science are religion-derived.

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