The Y chromosome is not the most important thing

X, Y and something else from genetics

Alexey Aleksenko, "Snob"

Why are people male and female? Biologists are one step closer to the answer.

At the risk of angering representatives of the most progressive lines of thought, let's start with the following statement: men are very different from women. Not as much, of course, as male anglerfish from females. In these deep-sea creatures, the differences are so great that zoologists for a long time did not just refer males to another species, but considered them some kind of parasite sucking the vital juices from the female. And yet the differences between the human sexes are also very revealing. Men from Mars, women from Venus – this is, of course, a poetic image, but there is quite legitimate surprise behind it: how creatures with almost identical genes can be so different.

Nettie Stevens, one of the first female geneticists, guessed how this happens in 1902. From her work, which was later brought to gloss by her boss, Edmund Beecher Wilson, follows the same story with the X and Y chromosomes, which everyone has undoubtedly heard about. In the original naive version, the situation looked like this: "female" genes are located on the X chromosome, "male" genes are located on the Y chromosome, and when both are present, the male ones overpower.

It took more than a hundred years to figure out the details. It may take as much more. Nevertheless, the recent scientific work of Dr. Robin Lovell-Badge from London and his colleagues gives reasons for optimism.

Here is one of the problems that Nettie Stevens didn't know about: sometimes there are no "male" genes on the Y chromosome at all. In drosophila flies, for example, sex is determined solely by the number of X chromosomes. In humans, the male chromosome is not so meaningless, although it contains mainly "garbage" sequences that do not encode anything. However, one important gene, called SRY (from the words Sex-determining Region on Y), still lurks among this junk. This gene, as is often the case with animal genes, is exclusively occupied with the fact that it includes other genes – and it depends on them which way the development of a living being will go. Will he develop curls, bows, dreaminess and the ability to procreate, or, on the contrary, a mustache, determination and the habit of turning around on every skirt.

Among the genes affected by SRY, the SOX family stands out, and among them is the SOX9 gene. It is not physically connected to the Y chromosome in any way, but is located on the most ordinary chromosome No. 17 - the one that both men and women have exactly two copies of. Meanwhile, he is probably the most important in this whole chain. When geneticists managed to include this gene by force, bypassing the usual events, the embryos developed exclusively into boys, regardless of what sex chromosomes they had there. More precisely, they developed into male mice: it is on mice, fortunately, that it is customary to conduct such experiments.

The picture emerged as follows: when it comes time for a lump of cells in the mother's womb to decide who to be, the SRY gene on the Y chromosome (if there is one) triggers various other genes, including SOX9. And after a little warm-up, he finally takes command. Let's repeat once again: this newly appointed commander has nothing to do with sex chromosomes anymore. Therefore, apparently, it turned out to be so easy for many animals, for example, crocodiles, to completely abandon the services of sex chromosomes and determine the sex of the embryo depending on the pressing tasks – for example, in accordance with the temperature of egg development.

It remains to understand exactly how this mysterious SOX9 is turned on. The difficulty here is this: most animal genes are busy turning on, off, strengthening or weakening each other. When theoretical biologists tried to estimate the genetic complexity of a person in the early 1960s, they found that there was no way to do with fewer genes than a million. But then it turned out that we only have a little over twenty thousand genes. However, the figure "million" soon also appeared. This is the value estimated by the number of "enhancers" – fragments of the genome, through which all this regulation of some genes by others takes place. One human gene accounts for an average of fifty enhancers, that is, it participates in five dozen different regulatory mechanisms. That's where all our complexity comes from.

British geneticists decided to sort out these very enhancers that control the single SOX9 gene. The prepared reader can learn about the ingenuity they had to show from the original article in Science. To the unprepared, let's face it: very, very great ingenuity. The enhancers of this gene are scattered over a huge segment of a chromosome the size of the genome of a good bacterium, and the size of each of them is only a few hundred letters of the genetic alphabet. Imagine a thick detective novel with a volume of two million printed characters – it's like three average Agatha Christie novels. And the key to solving the mystery is contained in just one paragraph 557 letters long. After reading to the end, you start feverishly turning the pages back – you definitely remember that there was some kind of clue, but where?

British researchers have found a clue. Its length was exactly 557 letters, and it was found half a million letters from the denouement of the detective, that is, from the beginning of the gene itself. If these letters are removed from a mouse embryo with a Y chromosome, which should grow into a glorious moustached mouse male, his fate changes, and he becomes a lovely moustached mouse girl. This tiny piece of genetic text turned out to be more important for determining gender than the whole huge and meaningless Y chromosome, which we men, for some reason, are so proud of. It turns out that the most important event in our gender destiny does not happen at all on these X and Y chromosomes worn out by journalists, but on the modest seventeenth. It is she who one day forms a kind of tricky loop from the life of the embryo, so that enhancer No. 13, discovered by the British, turns out to be exactly opposite the point from where the gene reading should begin. And if our destiny is to become a man, then this enhancer is active and triggers the gene itself. In all other cases, it turns out to be a woman, which is also fine in its own way.

This last phrase needs clarification: unfortunately, not in all cases. For every five thousand human babies, one is born with one or another sexual development disorder. Such cases, when, for example, chromosomal analysis shows the presence of normal X- and Y-chromosomes, but the newborn does not have developed genitals, baffled doctors. The work of Dr. Dovell-Badge and his colleagues provides the key to understanding such anomalies, and in the future, perhaps, to treatment.

But doctors will take care of it. And for now we have our own little reason for joy: we have begun to understand a little better the origin of the amazing mystery – the existence of men and women with all their diverse and amazing differences. Scientists, however, had to work hard for this. But it was enough for the dear reader to read this not too long note.

This article was published in the Israeli weekly "Windows", a literary supplement to the newspaper "Vesti".

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