It turned out that “unreadable” genes work

Scientists from the Moscow Institute of Physics and Technology and the Engelhardt Institute of Molecular Biology have discovered a mechanism that allows reading genes that are not available under normal conditions. This effect is due to the presence of sequences in the genome recognized by blocker proteins. The obtained results will help to understand the mechanisms of protein expression.

The work was published in Scientific Reports. The genomes of organisms containing a nucleus are packed in a structure consisting of DNA, RNA, and binding proteins – chromatin. Usually, chromatin can be divided into two main forms, differing in the ability to read genetic information.

The unreadable part is a tightly wound DNA strand around proteins and is called heterochromatin. The second part (euchromatin) consists of free stretches of unwound DNA, which allows enzymes to use this part of the genome to synthesize RNA and proteins. For a long time, heterochromatin was considered a “silent” part of the genome that did not contain genes. This means that it should not contain genetic information that affects the external signs of the organism.

As scientists obtained genomic data from various organisms, it became clear that heterochromatin contains both inactive and active regions. The latter contain genes encoding proteins, so the structural features of heterochromatin have become a new subject for study. In particular, several hundred protein-coding genes have already been found in Drosophila in the regions of heterochromatin lying near the intersection of parts of chromosomes.

In the course of evolution, genes moved between euchromatin and heterochromatin of the fruit fly genome. Therefore, the location of the same genes in the chromatin structure can be different even in organisms belonging to the same genus – “Drosophila”. And although the movement of genes between euchromatin and heterochromatin during the evolution of the Drosophila genome is quite common, the mechanism that allows genes to adapt to a heterochromatin environment remained unclear.

“We investigated protein-coding genes located near chromosome centromeres, in the so-called pericentromeric heterochromatin,” says Alexander Rezvykh, PhD student at Moscow Institute of Physics and Technology. It turned out that next to these genes there are insulators – DNA sequences with which special insulator proteins bind, which block the signal coming from the genomic environment.

The scientists analyzed genes that moved between euchromatin and heterochromatin in Drosophila species separated by 40 million years of evolution. It turned out that DNA sequences recognized by insulator proteins are retained with almost all studied genes, regardless of their location in different parts of chromatin.

“We assume that the ability for local adaptation of genes in heterochromatic regions of the genome was predetermined by the content of insulator sites in the regulatory regions of these genes in their common ancestor.

In addition, we have shown that the majority of heterochromatin genes are associated not with one, but with many insulator proteins, which possibly compensate for each other’s function and ensure their normal functioning in a heterochromatic environment, ”adds Sergey Funikov, Researcher, Laboratory of Molecular Mechanisms biological adaptation of the V.A.Engelgardt Institute of Molecular Biology.

Scientists from the Marine Biological Laboratory (Woods Hole, USA), the University of Jyväskylä (Finland) and the Koltsov Institute of Developmental Biology also took part in the work.