Disappearing before our eyes
The human “male” Y chromosome is rapidly disappearing, having lost almost 87.5% of the genes responsible for protein production. Scientists have calculated that the risk of mutation in the Y chromosome is approximately five times higher than in other parts of our DNA. And it is quite possible that over time the Y chromosome in humans will completely cease to exist.
There are very few genes left on the small Y chromosome that are responsible for male development, the most important of which is Sry (Sex-determining region Y).
As it is known, the 6th-7th week of pregnancy. All embryos develop according to the female type until the 2nd week, but then the Sru gene located on the Y chromosome is activated and the testes that produce male hormones begin to develop in the fetus. It causes the embryo to develop according to the male type. Since testicles do not develop in children with mutations in the Sry gene, these embryos give birth to girls.
However, not only Sru, but also two other Sru that are not located on the sex chromosomes are important for male-type development. This is the Sox9 gene and the Sox9 “switch” located next to it – the Enh14 gene.
This makes it possible to trigger male-type development even in the complete absence of the Y chromosome, through hyperactivation of the Sox9 gene, which has been done experimentally in XX or X0 mice that should normally develop into females. In some species (for example, Japanese mice Tokudaia osimensis), this mechanism has already been implemented during evolution, when the Y chromosome was completely lost and sex was determined by regulation of the activity of the Sox9 gene.
“This is an important point, because it turns out that the Sry gene itself is located on the Y chromosome, but the actual ‘determiner’ of sex (Sox9) is located in a completely different location, not on the sex chromosome.” One of the leading researchers at the Institute of General Genetics. NI Vavilova RAS, Konstantin Krutovsky Professor at the Department of Genomics and Bioinformatics at the Siberian Federal University (SFU).
That is, in ordinary mice with a female sex chromosome set (XX) or no Y chromosome (X0), the activity of the Enh14 enhancer gene is increased by adding an additional copy of this gene (genome editing or injecting an “enhancer” of this gene) – they will then turn into males . In practice, it will be possible to control sex development in the human embryo with the help of similar manipulations,” says Krutovsky.
By the way, in nature there are several species of mice that have already lost their “game”. These are the previously mentioned Japanese voles Tokudaia osimensis (also known as Ryukian or spiny mice), mole voles of Transcaucasia, hairy voles of Japan, and North American voles.
Give me more genes
Sex in nature is regulated in different ways. A more evolutionarily advanced type of inheritance is believed to be a chromosomal type of inheritance, as in humans. But there is also regulation that uses the dose effect – “shed” more of a particular gene – and now you are already a man. In this way, for example, the sex of some turtles is regulated. In warmer conditions more females are born, in less warm conditions males are born.
“Humans have a chromosomal inheritance, but it is very rigid. If XY, it will definitely be male, and if XX, it will definitely be female. It has nothing to do with the environment. This ensures that the one-to-one ratio in this form is always maintained. In reality, slightly more boys are born for various reasons,” says Krutovsky.
However, according to the professor, it is also possible to artificially regulate gender in humans using the dose effect. This is exactly what scientists did to ordinary mice, inserting an enhancer gene into them.
Nowadays, the concentration of male or female hormones is artificially increased for the transition from male to female or male to female. This is essentially the same dose effect – if the genes that determine male sex are actively working in women (this is normally impossible because women do not have the male Y chromosome, where the “exchange” of these Sry genes occurs). place), then there will be male hormones that are produced naturally by the person’s own genes and are not entered into the body in the form of injections that transgender people receive. However, only secondary sexual characteristics can be affected by hormone injections and only to a limited extent after puberty. The primary ones will remain in place – what grows, grows.
According to Konstantin Krutovsky, it is possible to completely reprogram gender with the help of injection or genomic editing at the stages of embryo development, which will also affect the primary sexual characteristics. This mechanism can become fixed in the genome, become inherited, and often replace the Y chromosome if it is lost during human evolution.
“It would be very easy to edit, you increase the expression (activity) of a gene and you start developing completely into the male variant. This can be done by injection and you can possibly maintain that dose for a while, or you can stabilize and make the increased dose permanent through genome editing. If this is done in the early stages of development, before puberty, then the girl will no longer be able to develop primary female sexual characteristics, she will not have a vagina and breasts. Development will follow a purely masculine pattern. Or, on the contrary, you can suppress the activity of certain genes in boys and development will follow a purely feminine pattern. This is radically different from today’s picture of transition from one gender to another,” Konstantin Krutovsky concluded.
But before humanity has to think about who to congratulate on International Men’s Day, according to some calculations, thousands of years will pass, and according to others, millions of years.