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The researchers found in the genome of mammals thousands of unknown DNA sequences

 
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Last reviewed: 16.10.2021
 
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13 October 2011, 19:23

A colossal comparative study of the genomes of 29 mammalian species can lead to a revision of the principles of the functioning and organization of the human genome. Scientists managed to directly see the genetic "dark matter", the existence of which was already guessed for a long time. In previous studies comparing human and mouse DNA, an indirect conclusion was drawn that there are a significant number of regulatory sequences that do not encode proteins themselves but control the activity of other genes. But, unlike already known and characterized regulators, their existence remained in the field of hypotheses. That's why they were called "dark matter": it must necessarily be somewhere, but nobody can see it.

The team of researchers from the Massachusetts Institute of Technology (USA), together with colleagues from other world scientific centers, succeeded. For five years they were engaged in sequencing and comparing the genomes of 29 placental mammals, including humans, elephants, rabbits, bats, etc. For twenty of them, the genomic DNA sequence was first obtained for the first time. First of all, scientists were interested in those sequences that changed little from species to species. It was the high conservatism of such sites that made them suspect regulatory sequences.

And here is the result: 10,000 highly conserved sequences directly influencing the activity of the gene were detected, and more than 1,000 such that serve as the basis for the synthesis of regulatory RNAs with a complex structure. Scientists also found 2.7 million sites - potential targets for interacting with transcription factors that determine where and when the gene needs to work. In addition, 4,000 new coding sequences, with information on proteins, were detected. It must be said that although the human genome has been fully read, the functions of many DNA sequences remain unclarified. Dealing with only one genome, it is almost impossible to tell which site encodes the protein itself, and which performs the regulatory function. But when compared with other genomes, such a task is completely solvable.

Researchers have been able to follow the evolution of mammals for 100 million years at the molecular level. The adaptation of the organism to the changing conditions of the environment is reflected in the transformations in the regulation of the genome, in the recruitment and activity of that very "dark matter" (which is no longer so "dark"). For example, now you can find out which genes were made from a human monkey. Previously, there were about 200; part of them was responsible for the development of the brain and the structure of the limbs. Today, the number of such sequences in DNA has increased to 1,000.

Other times must come for medicine. A large number of diseases are associated with mutations directly in the coding region of DNA: these mutations spoil the structure of the proteins themselves. But even more diseases are caused by a violation in the regulation of gene activity - when the protein begins to be synthesized where it is not necessary, or not where necessary, or not in the quantities that are needed. So now with a new, detailed and expanded map of regulatory elements in the genome it will be possible to determine the true cause of many and many diseases.

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