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
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.