Transgender mice
British scientists turned a male mouse into a female without changing "his" genes
Biologists from the UK forced the male to "lose" the testes and all genitals and "grow" the ovaries and all other female secondary signs by removing a supposedly meaningless section in their DNA. The results of the experiments and photographs of the animals were published in the journal Science (Gonen et al., Sex reversal following deletion of a single distal enhancer of Sox9).
On the left is a mouse with sex chromosomes and female genitals, on the right is an ordinary (XX) female.
"For the first time, we managed to force an animal to completely change sex, changing not individual genes encoding proteins, but "junk" DNA. We suggest that this site, Enh13, may play a key role in various disorders of sexual development and among humans," said Robin Lovell–Badge, a geneticist at the Francis Crick Institute in London (in a press release, Non-coding DNA changes the genitals you're born with - VM).
All mammals and many bird species use special sex chromosomes to determine the sex of future offspring. For example, the presence of two X chromosomes in the genome of a human embryo will turn it into a girl, and one X and one Y chromosome into a boy. Where the "male" and "female" embryo growth programs are contained and what controls them, scientists do not yet know.
Over the past two decades, geneticists have discovered that two genes – Sox9 and Sry-control essential parts of this development program. The first gene is responsible for the transformation of germ cell blanks into future testes and their auxiliary cells, and the second for the "inclusion" of Sox9 at the moment when the embryo is "determined" with its sex.
Damage to Sry, as Lowell-Badge and his team found out back in 1991, leads to the fact that "female" embryos turn into full-fledged males capable of continuing their kind. This discovery led scientists to the idea that many disorders in sexual development should be associated with mutations in these genes, but they quickly discovered that when mutations in these genes in the DNA of "deviants" were often not.
Such failures forced scientists to look for the causes of such problems not in Sox9 and Sry themselves, but in how their protein "packaging" and the immediate environment are arranged, which strongly affects how often a cell can read DNA. Changes in their structure, as recent experiments by biologists show, can completely disable or activate the genes associated with them.
These experiments, as Lowell-Badge notes, led to the discovery of an extremely unusual piece of "junk" DNA located next to the Sox9 gene. This segment of the genome, named Enh13, causes the cell proteins to "untangle" the part of the chromosome inside which Sox9 is located, which, as scientists have suggested, increases its activity and launches a program of "male" development.
Guided by this idea, biologists checked what would happen if this section of DNA was damaged or temporarily disabled. To do this, they crossed mice in whose genome there was only one serviceable copy of Enh13, and followed how their offspring developed.
This trick led to completely unexpected consequences – all the "males" in the litter of such rodents not only did not lose their genitals, but also acquired ovaries and all female secondary sexual characteristics. As Lowell-Badge notes, this was completely unexpected for him, since scientists expected that only half of the rodents would change their gender, since another stimulator of Sox9 activity, the TES site, is present in their DNA.
A complete sex change, in turn, suggests that Enh13 plays a key role in the sexual development of mammals – damage or mutations in this section of "junk" DNA, according to scientists, should be the cause of most "failures" in the sexual development of humans and animals.
"Junk DNA occupies approximately 98% of our genome, and only 2% of its "letters" are protein-coding genes. If the removal of just one such segment completely changed the animal's organs, then one can imagine what consequences other changes of this kind will lead to. We have been trying for decades to understand which parts of the genome are associated with disorders in sexual development, and it seems that the answer to this question lies not in genes," Lowell-Badge concludes.
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