EXCESS OF SPECIAL LONG INTRONS DETECTED IN BRAIN GENES
30.06.2020
The research is published in the journal Plos One. It is known that DNA encodes information about the structure and functioning of living organisms. In this "book of life", sequentially, nucleotide by nucleotide, information about all proteins and RNA formed in the cell is recorded. A DNA fragment encoding information about a single protein is called a gene, and the method of "translating" a DNA sequence into an amino acid sequence of a protein is called a genetic code.
Back in the 1960s, the main properties of the genetic code were discovered, among which tripletness is important. This property means that three consecutive nucleotides (codon) encode one amino acid. So, for example, the nucleotide sequence ATG (adenine-thymine-guanine) encodes the amino acid methionine, which usually begins with all proteins of living organisms at the stage of synthesis.
Since the discovery of the genetic code, a lot of information has been obtained about the structure of genes in living organisms. It became known that the genes of eukaryotes (organisms with a nucleus) are "fragmented". Inside the gene, between the coding regions, called exons, there are non-coding DNA fragments - introns. When the RNA of such genes matures, introns are excised and exons stitched together - a process called splicing.
Scientists have various hypotheses about how and how long ago introns originated. In particular, the presence of introns makes possible alternative splicing - the process of selectively linking different exons, which makes it possible to obtain different protein sequences from the same gene. This ensures that the number of different proteins in cells is much higher than the total number of genes.
Distribution of relative positions of introns along transcripts / © journals.plos.org
Also, an important mechanism of gene evolution, in which introns participate, is the so-called "mixing of exons". In this process, for example, an “extra” exon can be added between two other exons of a gene during recombination. This is how new genes emerge.
Due to the availability of the complete sequence of the genomes of many organisms, today scientists are able to analyze in detail the evolution of introns. It is known that introns can have different lengths (from several tens of pairs to several hundred thousand base pairs), as well as different phases. Phase 0 introns are located between codons, phase 1 - after the first nucleotide of the codon, phase 2 - after the second.
Bioinformatics from MIPT and IMPB RAS analyzed how the length and phase of introns in humans and mice relate to each other. “Before us, it never occurred to anyone to study the relationship between the length of an intron and its phase - because common sense says that there should be no connection between them (as between a person's height and the color of his eyes, for example),” comments Evgeny Baulin. an employee of the Laboratory of Applied Mathematics of the Institute of Metrology and Biology and the Department of Algorithms and Programming Technologies of the Moscow Institute of Physics and Technology
Phase distribution of long introns / © journals.plos.org
To the surprise of the authors of the study, a group of genes was found containing an unusually large number of long (more than 50 thousand base pairs) phase 1 introns. Moreover, such genes were associated with the transmission of nerve impulses in the brain. After conducting a detailed analysis of numerous scientific publications, the researchers were able to piece together a puzzle of disparate facts into a coherent picture. It turned out that the presence of phase 1 introns in this group of genes is explained in most cases by the presence of a special amino acid sequence, a signal peptide, at the beginning of proteins.
The task of this peptide is to direct the protein to its place of work, in the case of the receptors of nerve cells, to the plasma membrane. In turn, the relatively long length of these introns is also indirectly related to the presence of a signal peptide. The signal peptide in such proteins is always located at the beginning of the molecule, and the DNA fragment encoding it is always located at the beginning of the gene. Namely, long introns are often found at the beginning of a gene, because they contain regulatory DNA sequences that are important for the synthesis of this protein.
As a result of the work, the authors were able to decipher a harmonious and integral picture of the mechanism of mixing exons and the participation of long phase 1 introns in it. “This mechanism ensures the accelerated evolution of intercellular and membrane proteins in animals, in particular, the youngest of them - proteins that ensure the transmission of nerve impulses in brain cells,” concludes Evgeny Baulin.
Back in the 1960s, the main properties of the genetic code were discovered, among which tripletness is important. This property means that three consecutive nucleotides (codon) encode one amino acid. So, for example, the nucleotide sequence ATG (adenine-thymine-guanine) encodes the amino acid methionine, which usually begins with all proteins of living organisms at the stage of synthesis.
Since the discovery of the genetic code, a lot of information has been obtained about the structure of genes in living organisms. It became known that the genes of eukaryotes (organisms with a nucleus) are "fragmented". Inside the gene, between the coding regions, called exons, there are non-coding DNA fragments - introns. When the RNA of such genes matures, introns are excised and exons stitched together - a process called splicing.
Scientists have various hypotheses about how and how long ago introns originated. In particular, the presence of introns makes possible alternative splicing - the process of selectively linking different exons, which makes it possible to obtain different protein sequences from the same gene. This ensures that the number of different proteins in cells is much higher than the total number of genes.
Distribution of relative positions of introns along transcripts / © journals.plos.org
Also, an important mechanism of gene evolution, in which introns participate, is the so-called "mixing of exons". In this process, for example, an “extra” exon can be added between two other exons of a gene during recombination. This is how new genes emerge.
Due to the availability of the complete sequence of the genomes of many organisms, today scientists are able to analyze in detail the evolution of introns. It is known that introns can have different lengths (from several tens of pairs to several hundred thousand base pairs), as well as different phases. Phase 0 introns are located between codons, phase 1 - after the first nucleotide of the codon, phase 2 - after the second.
Bioinformatics from MIPT and IMPB RAS analyzed how the length and phase of introns in humans and mice relate to each other. “Before us, it never occurred to anyone to study the relationship between the length of an intron and its phase - because common sense says that there should be no connection between them (as between a person's height and the color of his eyes, for example),” comments Evgeny Baulin. an employee of the Laboratory of Applied Mathematics of the Institute of Metrology and Biology and the Department of Algorithms and Programming Technologies of the Moscow Institute of Physics and Technology
Phase distribution of long introns / © journals.plos.org
To the surprise of the authors of the study, a group of genes was found containing an unusually large number of long (more than 50 thousand base pairs) phase 1 introns. Moreover, such genes were associated with the transmission of nerve impulses in the brain. After conducting a detailed analysis of numerous scientific publications, the researchers were able to piece together a puzzle of disparate facts into a coherent picture. It turned out that the presence of phase 1 introns in this group of genes is explained in most cases by the presence of a special amino acid sequence, a signal peptide, at the beginning of proteins.
The task of this peptide is to direct the protein to its place of work, in the case of the receptors of nerve cells, to the plasma membrane. In turn, the relatively long length of these introns is also indirectly related to the presence of a signal peptide. The signal peptide in such proteins is always located at the beginning of the molecule, and the DNA fragment encoding it is always located at the beginning of the gene. Namely, long introns are often found at the beginning of a gene, because they contain regulatory DNA sequences that are important for the synthesis of this protein.
As a result of the work, the authors were able to decipher a harmonious and integral picture of the mechanism of mixing exons and the participation of long phase 1 introns in it. “This mechanism ensures the accelerated evolution of intercellular and membrane proteins in animals, in particular, the youngest of them - proteins that ensure the transmission of nerve impulses in brain cells,” concludes Evgeny Baulin.
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