6,500 Genes Expressed Differently in Men and Women Identified
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.
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 gene expression 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 women’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 harmful mutations weeded out or tolerated in the population? Indeed, the researchers found that the efficiency of selection is weaker in many such genes.
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.
“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.”
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.
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