Geneticists have discovered a piece of DNA that, when turned off, prevents the body from becoming a male. It has now been studied only in mice. The discovery will help explain the phenomenon of female organisms with a male set of chromosomes and will help to understand the similar mechanisms of occurrence of many diseases. The research is published in the journal Science.
In the first weeks of life, in most mammalian embryos, only genes on the “female” X chromosome are active, while the “male” Y chromosome turns on later. If it is still not activated, then all embryos will turn into females. The SRY gene on the Y chromosome is responsible for the partial suppression of female traits and the development of male traits. It indirectly activates another gene, Sox9, which is directly responsible for the formation of male genital organs. Biologists knew that one or more enhancers are involved in this process - regions of DNA outside genes that do not encode proteins, but serve to attach enzymes that read genetic information to them. The human genome contains about one million enhancers that control the activity of 21,000 genes. Therefore, finding the right piece of DNA is difficult enough.
In the new work, geneticists at the Francis Crick Institute in London have used several methods to find the desired enhancers in mouse embryos. They found 16 candidates, and further experiments made it possible to single out one of them. It is 557 nucleotides long and is located half a million bases from Sox9. In order for such a distant site to affect the gene, a special loop is formed in the chromosome. Disabling this enhancer made Sox9 less active, which is why all embryos with such a change turned into females, regardless of the set of chromosomes.
In addition to the fundamental importance that is important in order to elucidate the mechanisms of sex determination in animals, the work can also be useful in medicine. About one in 5,500 babies is born with a male set of chromosomes, but no male genitals are formed. Now the causes of this developmental disorder can be established in less than half of the cases. "This enhancer is so important in mice that it is likely to have a significant impact on human development," said team leader Robin Lowell-Badge. "It may be possible to apply the knowledge gained in order to understand and even change the functions of the genitals [in humans]."