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

The detailed mapping of the differences in gene expression serves as evidence that separate evolutionary processes take place in men and women, even if they are interdependent

Illustration: Weizmann Institute magazine.
illustration: Weizmann Institute Magazine.

Women and men differ from each other in different ways, for example in the risk of contracting certain diseases or in the way they react to medications. What are these differences, and how can they be explained? Researchers from the Weizmann Institute recently discovered thousands of human genes that are expressed, that is, activated, differently in each of the two sexes. The detailed mapping of the differences in gene expression between men and women, published in the scientific journal B.M.C. Biology, serves as evidence that separate evolutionary processes take place in males and females, even if they are interdependent.

Already several years ago they tried Prof. Shmuel Pitrokovsky And Dr. Moran Gershoni, from the Department of Molecular Genetics, to answer the question: Why is the incidence of certain diseases in the population higher than one would expect? For example, the two pointed out that the prevalence of fertility problems reaches up to 15% among couples in the Western world, apparently contrary to the simple evolutionary logic, according to which genetic mutations that harm fertility should have been sifted through the mechanisms of natural selection due to their direct effect on the number of offspring. Pitrokovsky and Gershoni showed in their research that mutations in genes related to sperm production manage to spread in the population precisely because many of these genes are expressed only in men. Therefore, a genetic mutation that causes "problems" in only half of the population - no matter how substantial - will be passed on to the next generation without interruption by the other half.

The more specific a gene was to one of the species, the lower the efficiency of the natural selection mechanisms we saw," Gershoni says. "Furthermore, among males, the efficiency of natural selection was even lower"

In the current study, the researchers sought to test their hypothesis widely, by mapping the expression of all the genes in the genome as a function of sex, men versus women. To this end, the scientists turned to the GTEx project, a large-scale study of the expression of human genes in the organs and tissues of approximately 550 adult donors. This project made it possible for the first time to carry out an extensive mapping of the genetic architecture of the sexes - men and women. Pitrokowski and Gershoni closely examined about 20,000 protein-coding genes, looking for differences in expression depending on the sex in each organ and tissue. The two identified about 6,500 genes in which there was biased activity towards one species or another in at least one tissue. For example, they identified genes that were prominently expressed in the skin of men, and found that these genes are important in the growth processes of body hair. Also, genes related to muscle building and contraction were overexpressed in men, while genes involved in fat storage showed overexpression in women.

In the next step, to understand how the mechanisms of natural selection work on genes unique to men or women, the researchers analyzed the tendency of harmful mutations to accumulate in the human population. In accordance with the hypotheses, the researchers found that the effectiveness of natural selection is less for these genes. That is, harmful mutations that cause risk or increase the risk of developing significant health problems manage to pass on to future generations and spread in the population, because they are inherited without interruption by the opposite sex. "The more specific a gene was to one of the species, the lower the effectiveness of natural selection mechanisms," says Gershoni. "Furthermore, among males, the efficiency of natural selection was even lower." Although the researchers do not have a complete explanation for this, they mention a theory that was first proposed in the 30s. "In many species", explains Pitrokowski, "females can give birth to a limited amount of offspring, while males, theoretically, are almost unlimited. Thus, the prosperity of the entire species depends to a greater extent on the number of breeding females, and is less affected by the number of breeding males. Perhaps this is the reason why 'natural selection' can be less severe when it comes to genes that are harmful only to males."

Precisely genes in which there are differences in expression between men and women are, paradoxically, the genes that directly affect human fertility and his ability to pass on the same mutations to the next generation."

Apart from the reproductive system, the researchers discovered quite a few genes that are active differently in women and men also in the mammary glands. This in itself is not surprising, but about half of these genes were overexpressed specifically in men. Since men have all the tissues necessary for lactation, even if in an inactive form, the scientists hypothesize that the role of some of these genes is to degenerate the tissues intended for milk secretion in men. Other organs where many genes with expression differences between women and men were found were the heart, brain and liver. One of these genes is found with almost exclusive expression in the hearts of young women, but is also associated with calcium absorption in bones. The scientists believe that this gene provides protection to the female heart until menopause and the cessation of the menstrual cycle, but after that, when its expression in women ceases, the risk of women developing heart disease and bone loss (osteoporosis) increases significantly. The exact role of another gene, whose specific activity was evident in the brains of women, is unknown, but the researchers believe that it protects certain nerve cells from Parkinson's disease, which is more common in men, and usually develops in them at younger ages. Several genes were also found with overexpression in the liver of women. These genes take part in the processes of breaking down drugs in the liver, and this may explain - at the molecular level - the known difference between the sexes in response to drugs.

"The human genome is almost identical in each of us, but it is activated differently in different organs and in different people," Gershoni says. "When it concerns the differences between the species, it can be seen that evolution works at the level of gene expression." Pitrokowski adds: "Exactly genes in which there are expression differences between men and women, and mutations in which can 'escape selection' and spread in the population, are paradoxically the genes that directly affect a person's fertility and his ability to pass those mutations on to the next generation." From this point of view, different pressures of natural selection are exerted on men and women, and at least to some extent, human evolution should be seen as a "co-evolution" of men and women.

8 תגובות

  1. Small detail: the GTEx repository is for dead people. The tissues from each person were taken at completely different times after death (sometimes even weeks and months) and in my eyes it is difficult to compare differences between women and men when the body has been dead for some time.

  2. We learned that the activity of certain identical genes is expressed differently in women and men.
    It follows that there is a gene that is responsible for sorting out the difference in the expression of those genes, between women and men. We call this gene GSBM (the gene for the difference in expression between the species)
    The immediate logic says that, this gene sits on the sex chromosomes X in women and Y in men.
    In this context, two points can be noted:
    1). It is possible that with the technology of genetic engineering it is possible to compare the distinguishing features of GSBM on the X and Y chromosomes, thereby blocking the possibility of the spread of "anti-evolutionary" features such as the problem of genetic infertility (mentioned in the article), in each of the species, and such as hereditary transmission of incurable diseases.
    A scientist who succeeds in actually carrying out this interview will surely win many prizes and maybe even the Levon Prize (or the reverse of the Nobel).
    2). If the remaining existence of the GSBM is indeed correct, then there is a lack of symmetry between men and women. Men have one Y gene and one X gene. Hence, it is possible that on the X gene in men there is a GSBM gene with female genetic sorting properties.
    Hence, in men, the GAS gene on the Y chromosome is often (but probably not always!) dominant and its effect in males outweighs the effect of the female GAS on the X chromosome.
    However, sometimes there is no such dominance of GPS Y over GPS X. Or then a hybrid (combined) expression of different sexual traits can arise resulting from a combined effect of GPS-Y and GPS-X.
    It is possible that this is the genetic reason for the formation of bisexual and androgynous traits.

  3. No.
    As you know, breast cancer also occurs in men.
    Since there is a connection between cancer and the female hormone, it appears more in women,
    But also appears in men.
    On the other hand, cervical cancer does not appear in men for some reason, and prostate cancer does not appear in women, I wonder why.

    I once read an article about the fact that in the past it was thought that every carrier of the XX gene would always be female and every carrier of XY was male...
    Since there were several female athletes in the Olympics who were in doubt as to whether they were female or male (who underwent gender reassignment surgery), they decided to perform a gene test on female athletes.
    In one of the tests, a perfect female with the XY gene was discovered, the same athlete also gave birth to children later.
    Following this case, the matter was investigated and it was discovered that what determines the classification of the fetus as male or female are hormones that are secreted by the mother during pregnancy - it is not the mother's body that knows whether it is XX or XY and secretes hormones according to the sex of the fetus that is supposed to develop, but in situations of distress and stress or a problem Otherwise the mechanism may go wrong and children are born with a different sexual identity than their genes - for example male children with female tendencies and vice versa, children with different genitalia and so on.

  4. Interestingly, the most common cancer in women is also unique to women, as is the case with men. Not sure it's related at all.
    The theory sounds interesting and convincing but on the other hand it is based on fertility problems in modern society. And in this matter, even if there is a genetic component, it is a problem that has become very acute in the modern era, and it makes more sense that our way of life is the one that causes the problems to manifest (it is known that even if there is a genetic defect, it will not always be sufficiently expressed. And it is also affected by environmental reasons) and if so it is clear why evolution does not Swinging those genes, she had no reason as long as the life form didn't make the genes work. This is also true for the types of cancer that are known to have a steep increase in their incidence such as breast cancer.
    Yaron
    It should not be particularly surprising that most of the differences between women and men are not differences in genes but only in their expression. This explains how a change in the relationship between the hormones alone can eliminate a large part of the external differences or how it is that there are those who are born with a double reproductive system (female and male genitals) even though in terms of chromosomes they are only male or only female.

  5. 6700 genes out of 21,000 human genes in total. I don't come from the field of genetics, that's what a google search showed. That means 1/3 of the genes are expressed differently and not different from each other.

  6. The title should be refined. The same genes are expressed differently between men and women. If there were different genes between men and women it would be two different species. Between us and chimpanzees there is approximately 1.5% genetic difference. Different species are usually unable to breed with each other and produce fertile offspring.

  7. interesting!
    If I understood correctly, it can be assumed that statistically it will be possible to find a higher correlation between women's fertility problems and similar problems in their father's family, and men's fertility problems - with their mother's side of the family.

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