Not garbage at all
Suddenly: the "jumping gene," considered junk, is crucial for embryo development
Yulia Vorobyova, Vesti, based on University of California San Francisco: Not Junk: 'Jumping Gene' is Critical for Early Embryo
When scientists first learned in the 1950s how DNA encodes instructions for the production of proteins from which the entire body is built, they assumed that absolutely all human genetic information was important. But by the 1970s it became clear that only 1% of our genome encodes functional (working) proteins, and some parts of DNA perform completely different tasks, for example, regulate the activity of genes encoding proteins.
At that time, geneticists came to the conclusion that about 90% of our genome is completely useless. However, later this idea began to undergo changes, for example, in 2017 it was proved that 75% of DNA is useless, although harmless to the body, genetic material. It is also called non-coding, or garbage.
However, not all experts were convinced of the complete uselessness of such a part of DNA. And they were right.
In the new work, a team from the University of California, San Francisco studied one of the "jumping genes", also known as transposons. This term refers to sections of DNA capable of movement (transposition) and reproduction within the genome.
Such mobile genetic elements, as experts specify, make up half of our entire DNA. They are considered virus-like genetic garbage. It is known that in the course of evolution, some "jumping genes" left hundreds or even thousands of variants scattered throughout the genome of a living organism. And if most of them are considered inactive, then others can create real genetic chaos by changing or disrupting the normal genetic programming of cells, which causes dangerous diseases, for example, cancer.
Miguel Ramalho-Santos, who led the new study, has been studying transposons since 2003. The scientist focused on a group of "jumping genes" under the general name LINE1, one of the most common (accounting for more than 20% of the human genome).
These genes, like many others, were considered a "genetic parasite", but now a team of geneticists and reproductologists has proved that in fact they are an important regulator of embryonic development in the early stages.
The researchers noticed that embryonic stem cells, as well as embryos at the very first stages of development, actively generate proteins, thanks to the genes of the LINE1 group. This trend seemed illogical, because these genes can be potentially dangerous, Ramalho-Santos explains.
"These early embryos were really playing with fire. It just didn't make any sense, and I wondered if something else was going on," the scientist recalls.
Co-author of the work Michelle Percharde (Michelle Percharde) argues: "When I saw all the LINE1 RNA present in the nucleus of developing cells, I agreed that it should play a role. Why do cells produce so much of this RNA if it's either dangerous or useless?". Recall that an RNA molecule is created in a cell "on the basis" of DNA.
The experts decided to find out what caused the high levels of expression of the genes of the LINE1 group on the example of mouse embryos. When they eliminated the RNA encoded by these genes from embryonic stem cells, they saw that the expression of the genes had changed. The cells seemed to have "changed their personality" and demonstrated the expression of the genes of the sample of the so-called two-cell phase, into which the embryo passes after the first division of the fertilized egg.
In another experiment, the researchers deprived the fertilized eggs of the LINE1 genes themselves, and as a result, the embryos completely lost the ability to reach the next stage of development after the two-cell one.
Further experiments confirmed that the role of LINE1 genes is not to copy and paste new genetic material into different parts of the genome without control. Instead, the experts saw that the LINE1 RNA enters the cell nucleus, where it forms a complex compound with two protein regulators of genes.
The resulting complex disables the dominant genetic program, which is responsible for the formation of two cells of the embryo, and includes genes that are necessary for further division. In other words, without the participation of the LINE1 genes, the embryo simply "gets stuck" at this stage and cannot develop further.
The team plans to continue studying the role of "jumping genes" and hopes that other scientists will pay attention to their functionality and eventually become convinced of the usefulness of "genetic parasites".
"These genes have been with us for billions of years and have occupied most of our genome for hundreds of millions of years. I think it's fairer to ask whether 1.5% of the genes encoding proteins are "stowaways", and not vice versa," Ramalho–Santos believes.
In his opinion, transposons like LINE1 help the embryo to go through a difficult early stage of development precisely because they are so common. Since LINE1 repeats thousands of times in the genome, it is almost impossible for any mutation (and there are, as you know, a lot of them) to lead the genetic program astray. Even if one copy is "corrupted", there will still be a lot of "correct" copies that will allow the embryo to develop into a full-fledged organism.
"This can be a very reliable mechanism for regulating development," the researcher concludes.
A scientific article based on the results of this work was published in Cell (Percharde et al., A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity).
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