There is less and less garbage in the DNA
Genetic debris hid the coding areaAlla Solodova, Infox.ru
Geneticists will have to revise the mechanisms of DNA.
One of the sequences, which belonged to non-coding ("garbage") sites, was involved in the synthesis of one of the most important proteins of the human body.
Most of the human genome consists of non-coding or, as it is otherwise called, junk DNA. This part of the nucleotide sequence is present in chromosomes, but does not carry any information. When reading the "genetic cipher", special enzymes cut out non-coding sections from the primary copy of DNA. Further, other enzymes glue significant sequences of nucleotides into mRNA, from which proteins are synthesized as from the matrix (which is why it was called matrix).
As a rule, such non—coding sequences (introns) are located stationary - between functional DNA sites (exons). But there are also mobile non-coding nucleotides that move through the genome and periodically wedge into genes, causing chromosomal rearrangements and mutations.
Infected genomeThe human genome consists of more than 40% of various mobile genetic sequences — retrotransposons.
Moreover, among the genetic travelers there are also endogenous (internal) retroviruses that infect human DNA. They store information in RNA and contrary to the usual pattern of DNA → RNA → protein, retroviruses transmit genetic information in the opposite direction. Viral DNA is synthesized on the basis of RNA and then embedded in the human genome. In this way, viral DNA receives a "residence permit" in the genetic community and, together with human genes, is transmitted from generation to generation.
According to scientists, do not be afraid of such viruses — about 8% of the human genome consists of "contagious" DNA. And a person picked up this genetic "infection" quite a long time ago — tens of millions of years ago and is still alive. Moreover, it is possible that it is thanks to such genetic viruses that the most significant evolutionary changes and transformations have occurred.
The remaining 32% of the genetic mobile garbage is accounted for by three "families" of nucleotide sequences of different lengths and with varying degrees of repeats — LINE, SINE and LTR. Scientists are sure that most retrotransposons at least do not bring any benefit to the human genome, and in some cases they also cause harm. In a word, most of the genetic garbage is rightfully called "garbage". These assumptions were confirmed even more after Malone CD and Hannon GJ published an article Small RNAs as guardians of the genome in Cell magazine in 2009. According to the results of the study, they described the molecular mechanism by which the "host" cell suppresses any attempts of retrotransposons to show activity.
Functional garbageNevertheless, many genetic viruses and non-coding sequences still influence the synthesis of mRNA and protein, respectively.
Many of them are located in meaningless (intronic) sections of DNA at a distance of up to several hundred thousand bases from the gene with which they are functionally related. That is, it may not be immediately clear that the "garbage" in the far corner of the chromosome can somehow "stay in touch" with a functional gene.
One of the common "junk" mobile nucleotide sequences is the long terminal repeat of endogenous retrovirus—9 (ERV-9 LTRs). This mobile genetic element has been repeatedly noticed in connection with a number of hematological diseases. It is located at a distance of 40-70000 nucleotide bases from the genes that encode the fetal and adult forms of the globin protein. Interestingly, ERV-9 LTR interacts with not one, but almost ten human genes that are located near the genes of the globin protein
In the human and chimpanzee genome, ERV-9 LTR has a visible effect on the functional activity of embryonic and blood stem cells. Researchers from the Medical College of Georgia decided to test the role of ERV-9 LTR in the synthesis of "blood" protein. To do this, scientists raised transgenic mice with a 100,000-base-pair locus embedded in their genome containing globin protein genes. The genome of transgenic mice from the experimental group contained genetic garbage, and the genome of mice from the control group was "cleaned" by scientists from ERV-9 LTR.
And still not junkScientists have studied chromatin and proteins that are involved in the realization of genetic information.
It turned out that ERV-9 LTR does not just regulate the work of fetal and adult globin genes, but "turns on" the expression of these genes on a competitive basis. The researchers described the molecular mechanism by which ERV-9 LTR creates competition between two types of globin.
In the absence of ERV-9 LTR in the cell, the level of all proteins involved in the synthesis of adult globin significantly decreases. It is known that the inclusion of adult globin genes in the work automatically turns off fetal globin genes and vice versa. In the experiment, scientists once again confirmed this and showed that the main target of ERV-9 LTR are the genes of an adult globin. That is, it is he who forces hematopoietic cells to implement encoded information and synthesize a protein for adult hemoglobin.
Biologists also tracked ERV-9 LTR in blood stem cells and in embryonic cells. It turned out that ERV-9 LTR is most active in erythroid stem cells.
Based on the data obtained, geneticists came to the conclusion that out of 4,000 copies of ERV-9 LTR that are present in the human genome, at least a few sequences do not clog DNA, but help cells perform their functions and give some advantages in competitive protein synthesis. So now geneticists will have to revise the garbage parts of the genome to check whether they are not involved in the already seemingly studied mechanisms of certain genes.
Detailed results of the study are published in the article Long-range function of an intergenic retrotransposon in the journal PNAS.
Portal "Eternal youth" http://vechnayamolodost.ru07.07.2010