Useful garbage
"Junk DNA" should not be thrown away!
Alexandra Bruter, <url>
In the 60-70s, at the dawn of genomic research, the term "junk DNA" (junk DNA) was coined and perfectly caught on. This term appeared when it became clear that a bunch of mutations did not cause any changes in the phenotype at all, which meant that not all DNA encodes proteins. In the human genome, proteins encode approximately 2% of DNA. Since everything incomprehensible is easy and pleasant to declare unnecessary, the name "garbage" has been fixed for the rest of the DNA. Over the past decade, however, the percentage of junk DNA in the human genome has noticeably decreased, and the point here is not the rapid evolution of the human genome, but closer studies of the remaining 98%.
An article published in Cell Reports (Fasching et al., TRIM28 Represses Transcription of Endogenous Retroviruses in Neural Progenitor Cells) is devoted to the role of one of the varieties of non–protein–coding DNA - Endogenous Retroviruses - in the development of nerve cells.
The cells that make up the nervous system are very different. There are more than a thousand types of neurons alone. At the same time, of course, their genomes are the same both among themselves and with the vast majority of other cells of the body. The question arises as to how these differences appear. In order for the cells to be different, it is necessary that the genes in them (at least at the stage of development) are active in different ways, that is, different proteins are synthesized.
The main method of regulating gene activity today is chemical modification, methylation – the attachment of methyl groups of atoms to some cytosines – the constituent elements of DNA. In addition, there are many varieties of regulatory RNAs. Usually they interact with the already synthesized matrix DNA corresponding to the gene and cause its degradation, thus rendering the gene inactive.
Recently, there has been evidence that former viruses, which are part of the genomes of almost all complex organisms in large numbers, also play a role in regulating gene activity.
Endogenous retroviruses make up approximately 8-10% of the human and mouse genome. Where did they even come from there? When a virus infects a cell, it embeds its genome into the DNA of the cell. If it is a pathogenic virus that causes an acute disease, it begins to multiply in full, the cell becomes ill, on the one hand, the virus harms it, on the other hand, it is attacked by the immune system, which detects viral particles on the cell surface. Probably, such a cell will die, and its copies of viral DNA will disappear from the body. But sometimes the infection of a cell with a virus occurs without all these effects, or for some reason the cell survives. Some pathogenic viruses, for example, HIV, infect not only T4 lymphocytes, which will eventually die, but also other cells in which backups are stored. The problem with HIV therapy is precisely that drugs are not able to destroy cells containing resting viral DNA in the genome. Generally speaking, if the virus is not very contagious, and a sick person cannot infect half a subway car with one sneeze, it is advantageous for him to behave quietly and live for a long time with one host.
Sometimes it happens that the virus embeds its genome, not into a somatic cell, but into a cell of the sexual line. If this particular cell takes part in the fertilization process, and a new organism develops from it, then all its cells will contain their own copy of the viral genome. In the future, this copy can be inherited. So, for many years of the evolution of wildlife, some species have accumulated a lot of viral sequences in the genome.
Of course, for an organism to be viable, viral sequences must become inactive. This usually happens, but inactivation is sometimes incomplete. For example, sometimes the activation of viruses leads to doubling of genes in the genome – the virus creates its own copy and takes the gene with it. Gene doubling plays a big role in evolution, because one of the copies obtained ceases to experience selection pressure and can mutate freely without affecting the phenotype.
It turned out that inactive viral fragments may contain active sequences that trigger or suppress the synthesis of RNA from nearby genes. In fact, such activity is fraught with the danger of certain genes getting out of control and the appearance of tumors. But it has been shown that viral elements are noticeably activated in nerve cells during their development. At the earliest stages of development, TRIM28 protein suppresses the activity of viral elements. Malfunctions in the work of this protein were considered to be associated with some mental disorders, for example, reduced stress tolerance.
Diagram from an article in Cell Reports – VM
In normal cells, TRIM28 is needed only at the first stage, even if it is turned off later, the viral elements are not activated again. In neural stem cells, everything happens differently. Without the constant supervision of this protein, some retroviruses activated themselves and began to regulate the activity of neighboring genes. The complete shutdown of TRIM28 turned out to be lethal for mice, and the shutdown of one copy of the gene led to behavioral disorders, in particular, hyperactivity.
It seems that viral sequences, although they got into the genome completely by accident, and seemed like garbage to scientists before, were still assigned to the task in the course of evolution – to regulate the activity of genes where chemical modifications of DNA for some reason do not fit.
Portal "Eternal youth" http://vechnayamolodost.ru14.01.2015