We all know that the appearance of a person, some habits and even diseases are inherited. All this information about a living being is encoded in the genes. So what do these notorious genes look like, how do they function, and where are they located?
So, the carrier of all genes of any person or animal is DNA. This compound was discovered in 1869 by Johann Friedrich Miescher. Chemically, DNA is deoxyribonucleic acid. What does this mean? How does this acid carry the genetic code of all life on our planet?
Let's start by looking at where DNA is located. There are many organelles in the human cell that perform various functions. DNA is located in the nucleus. The nucleus is a small organelle that is surrounded by a special membrane that stores all the genetic material - DNA.
What is the structure of a DNA molecule?
First, let's look at what DNA is. DNA is a very long molecule consisting of structural elements - nucleotides. There are 4 types of nucleotides - adenine (A), thymine (T), guanine (G) and cytosine (C). The chain of nucleotides schematically looks like this: GGAATTSTAAG.... This sequence of nucleotides is the DNA chain.The structure of DNA was first deciphered in 1953 by James Watson and Francis Crick.
In one DNA molecule, there are two chains of nucleotides that are helically twisted around each other. How do these nucleotide chains stick together and twist into a spiral? This phenomenon is due to the property of complementarity. Complementarity means that only certain nucleotides (complementary) can be opposite each other in two chains. So, opposite adenine is always thymine, and opposite guanine is always only cytosine. Thus, guanine is complementary with cytosine, and adenine with thymine. Such pairs of nucleotides opposite each other in different chains are also called complementary.
It can be schematically represented as follows:
G - C
T - A
T - A
C - G
These complementary pairs A - T and G - C form chemical bond between the nucleotides of the pair, and the bond between G and C is stronger than between A and T. The bond is formed strictly between complementary bases, that is, the formation of a bond between non-complementary G and A is impossible.
The "packaging" of DNA, how does a strand of DNA become a chromosome?
Why do these nucleotide chains of DNA also twist around each other? Why is this needed? The fact is that the number of nucleotides is huge and you need a lot of space to accommodate such long chains. For this reason, there is a spiral twisting of two strands of DNA around the other. This phenomenon is called spiralization. As a result of spiralization, DNA chains are shortened by 5-6 times.Some DNA molecules are actively used by the body, while others are rarely used. Such rarely used DNA molecules, in addition to helicalization, undergo even more compact “packaging”. Such a compact package is called supercoiling and shortens the DNA strand by 25-30 times!
How is DNA helix packaged?
For supercoiling, histone proteins are used, which have the appearance and structure of a rod or spool of thread. Spiralized strands of DNA are wound onto these "coils" - histone proteins. In this way, the long filament becomes very compactly packed and takes up very little space. If it is necessary to use one or another DNA molecule, the process of “untwisting” occurs, that is, the DNA thread is “reeled” from the “coil” - the histone protein (if it was wound on it) and unwinds from the helix into two parallel chains. And when the DNA molecule is in such a untwisted state, then the necessary genetic information can be read from it. Moreover, the reading of genetic information occurs only from untwisted DNA strands!
A set of supercoiled chromosomes is called heterochromatin, and the chromosomes available for reading information - euchromatin.
What are genes, what is their relationship with DNA?
Now let's look at what genes are. It is known that there are genes that determine the blood group, the color of the eyes, hair, skin and many other properties of our body. A gene is a strictly defined section of DNA, consisting of a certain number of nucleotides arranged in a strictly defined combination. Location in a strictly defined section of DNA means that a particular gene has its place, and it is impossible to change this place. It is appropriate to make such a comparison: a person lives on a certain street, in a certain house and apartment, and a person cannot arbitrarily move to another house, apartment or to another street. A certain number of nucleotides in a gene means that each gene has a specific number of nucleotides and cannot become more or less. For example, the gene encoding insulin production is 60 base pairs long; the gene encoding the production of the hormone oxytocin is 370 bp. A strict nucleotide sequence is unique for each gene and strictly defined. For example, the AATTAATA sequence is a fragment of a gene that codes for insulin production. In order to obtain insulin, just such a sequence is used; to obtain, for example, adrenaline, a different combination of nucleotides is used. It is important to understand that only a certain combination of nucleotides encodes a certain "product" (adrenaline, insulin, etc.). Such a unique combination of a certain number of nucleotides, standing in "its place" - this is gene.
In addition to genes, the so-called "non-coding sequences" are located in the DNA chain. Such non-coding nucleotide sequences regulate the functioning of genes, help chromosome spiralization, and mark the start and end points of a gene. However, to date, the role of most non-coding sequences remains unclear.
What is a chromosome? sex chromosomes
The totality of an individual's genes is called the genome. Naturally, the entire genome cannot be packed into a single DNA. The genome is divided into 46 pairs of DNA molecules. One pair of DNA molecules is called a chromosome. So it is precisely these chromosomes that a person has 46 pieces. Each chromosome carries a strictly defined set of genes, for example, the 18th chromosome contains genes encoding eye color, etc. Chromosomes differ from each other in length and shape. The most common forms are in the form of X or Y, but there are also others. A person has two chromosomes of the same shape, which are called paired (pairs). In connection with such differences, all paired chromosomes are numbered - there are 23 pairs. This means that there is a pair of chromosomes #1, pair #2, #3, and so on. Each gene responsible for a particular trait is located on the same chromosome. In modern manuals for specialists, the localization of the gene may be indicated, for example, as follows: chromosome 22, long arm.What are the differences between chromosomes?
How else do chromosomes differ from each other? What does the term long arm mean? Let's take X-shaped chromosomes. The crossing of DNA strands can occur strictly in the middle (X), or it can occur not centrally. When such an intersection of DNA strands does not occur centrally, then relative to the point of intersection, some ends are longer, others, respectively, are shorter. Such long ends are commonly called the long arm of the chromosome, and short ends, respectively, the short arm. Y-shaped chromosomes are mostly occupied by long arms, and short ones are very small (they are not even indicated on the schematic image). The size of the chromosomes fluctuates: the largest are the chromosomes of pairs No. 1 and No. 3, the smallest chromosomes of pairs No. 17, No. 19.
In addition to shapes and sizes, chromosomes differ in their functions. Out of 23 pairs, 22 pairs are somatic and 1 pair is sexual. What does it mean? Somatic chromosomes determine all the external signs of an individual, the characteristics of his behavioral reactions, hereditary psychotype, that is, all the features and characteristics of each individual person. A pair of sex chromosomes determines the sex of a person: male or female. There are two types of human sex chromosomes - X (X) and Y (Y). If they are combined as XX (x - x) - this is a woman, and if XY (x - y) - we have a man in front of us.
Hereditary diseases and chromosome damage
However, there are "breakdowns" of the genome, then genetic diseases are detected in people. For example, when there are three chromosomes in 21 pairs of chromosomes instead of two, a person is born with Down syndrome.There are many smaller "breakdowns" of genetic material that do not lead to the onset of the disease, but, on the contrary, give good properties. All "breakdowns" of the genetic material are called mutations. Mutations that lead to disease or a deterioration in the properties of the organism are considered negative, and mutations that lead to the formation of new useful properties are considered positive.
However, in relation to most of the diseases that people suffer today, it is not a disease that is inherited, but only a predisposition. For example, in the father of a child, sugar is absorbed slowly. This does not mean that the child will be born with diabetes, but the child will have a predisposition. This means that if the child abuses sweets and flour products he will develop diabetes.
Today, the so-called predicative the medicine. As part of this medical practice, predispositions are identified in a person (based on the identification of the corresponding genes), and then recommendations are given to him - what diet to follow, how to properly alternate work and rest regimes so as not to get sick.
How to read the information encoded in DNA?
But how can you read the information contained in DNA? How does her own body use it? DNA itself is a kind of matrix, but not simple, but encoded. To read information from the DNA matrix, it is first transferred to a special carrier - RNA. RNA is chemically ribonucleic acid. It differs from DNA in that it can pass through the nuclear membrane into the cell, while DNA lacks this ability (it can only be found in the nucleus). The encoded information is used in the cell itself. So, RNA is a carrier of coded information from the nucleus to the cell.How does RNA synthesis occur, how is protein synthesized with the help of RNA?
The DNA strands from which information must be “read” are untwisted, a special enzyme, the “builder”, approaches them and synthesizes a complementary RNA chain in parallel with the DNA strand. The RNA molecule also consists of 4 types of nucleotides - adenine (A), uracil (U), guanine (G) and cytosine (C). In this case, the following pairs are complementary: adenine - uracil, guanine - cytosine. As you can see, unlike DNA, RNA uses uracil instead of thymine. That is, the “builder” enzyme works as follows: if it sees A in the DNA strand, then it attaches Y to the RNA strand, if G, then it attaches C, etc. Thus, a template is formed from each active gene during transcription - a copy of RNA that can pass through the nuclear membrane. How is the synthesis of a protein encoded by a particular gene?
After leaving the nucleus, RNA enters the cytoplasm. Already in the cytoplasm, RNA can be, as a matrix, built into special enzyme systems (ribosomes), which can synthesize, guided by the information of RNA, the corresponding amino acid sequence of the protein. As you know, a protein molecule is made up of amino acids. How does the ribosome manage to know which amino acid to attach to the growing protein chain? This is done on the basis of a triplet code. The triplet code means that the sequence of three nucleotides of the RNA chain ( triplet, for example, GGU) code for one amino acid (in this case, glycine). Each amino acid is encoded by a specific triplet. And so, the ribosome “reads” the triplet, determines which amino acid should be added next as information is read into the RNA. When a chain of amino acids is formed, it takes a certain spatial form and becomes a protein capable of carrying out the enzymatic, building, hormonal and other functions assigned to it.Protein for any living organism is a gene product. It is proteins that determine all the various properties, qualities and external manifestations of genes.
8.1. Gene as a discrete unit of heredity
One of the fundamental concepts of genetics at all stages of its development was the concept of the unit of heredity. In 1865, the founder of genetics (the science of heredity and variability), G. Mendel, based on the results of his experiments on peas, came to the conclusion that hereditary material is discrete, i.e. represented by individual units of heredity. Units of heredity, which are responsible for the development of individual traits, G. Mendel called "inclinations". Mendel argued that in the body, for any trait, there is a pair of allelic inclinations (one from each of the parents), which do not interact with each other, do not mix and do not change. Therefore, during sexual reproduction of organisms, only one of the hereditary inclinations in a "pure" unchanged form enters the gametes.
Later, G. Mendel's assumptions about the units of heredity received complete cytological confirmation. In 1909, the Danish geneticist W. Johansen called Mendel's "hereditary inclinations" genes.
Within the framework of classical genetics, the gene is considered as a functionally indivisible unit hereditary material, which determines the formation of some elementary feature.
Various variants of the state of a particular gene, resulting from changes (mutations), are called "alleles" (allelic genes). The number of alleles of a gene in a population can be significant, but in a particular organism the number of alleles of a particular gene is always equal to two - according to the number of homologous chromosomes. If in a population the number of alleles of any gene is more than two, then this phenomenon is called "multiple allelism".
Genes are characterized by two biologically opposite properties: the high stability of their structural organization and the ability to hereditary changes (mutations). Thanks to these unique properties, it is ensured: on the one hand, the stability of biological systems (invariability in a number of generations), and on the other hand, the process of their historical development, the formation of adaptations to conditions environment, i.e. evolution.
8.2. Gene as a unit of genetic information. Genetic code.
More than 2500 years ago, Aristotle suggested that gametes are by no means miniature versions of the future organism, but structures containing information about the development of embryos (although he recognized only the exceptional importance of the egg to the detriment of the spermatozoon). However, the development of this idea in modern research became possible only after 1953, when J. Watson and F. Crick developed a three-dimensional model of the structure of DNA and thereby created the scientific prerequisites for revealing the molecular foundations of hereditary information. Since that time, the era of modern molecular genetics began.
The development of molecular genetics has led to the disclosure of the chemical nature of genetic (hereditary) information and has filled with concrete meaning the idea of a gene as a unit of genetic information.
Genetic information is information about the signs and properties of living organisms, embedded in the hereditary structures of DNA, which is realized in ontogeny through protein synthesis. Each new generation receives hereditary information, as a program for the development of an organism, from its ancestors in the form of a set of genome genes. The unit of hereditary information is a gene, which is a functionally indivisible section of DNA with a specific nucleotide sequence that determines the amino acid sequence of a particular polypeptide or RNA nucleotides.
Hereditary information about the primary structure of a protein is recorded in DNA using the genetic code.
The genetic code is a system for recording genetic information in a DNA (RNA) molecule in the form of a specific sequence of nucleotides. This code serves as a key for translating the nucleotide sequence in mRNA into the amino acid sequence of the polypeptide chain during its synthesis.
Properties of the genetic code:
1. Tripletity - each amino acid is encoded by a sequence of three nucleotides (triplet or codon)
2. Degeneracy - most amino acids are encrypted by more than one codon (from 2 to 6). There are 4 different nucleotides in DNA or RNA, which theoretically can form 64 different triplets (4 3 = 64) to code for 20 amino acids that make up proteins. This explains the degeneracy of the genetic code.
3. Non-overlapping - the same nucleotide cannot be part of two adjacent triplets at the same time.
4. Specificity (uniqueness) - each triplet encodes only one amino acid.
5. The code has no punctuation marks. Reading information from mRNA during protein synthesis always goes in the direction 5, - 3, in accordance with the sequence of mRNA codons. If one nucleotide falls out, then when reading it, the nearest nucleotide from the neighboring code will take its place, which will change the amino acid composition in the protein molecule.
6. The code is universal for all living organisms and viruses: the same triplets encode the same amino acids.
The universality of the genetic code indicates the unity of the origin of all living organisms
However, the universality of the genetic code is not absolute. In mitochondria, the number of codons has a different meaning. Therefore, sometimes one speaks of the quasi-universality of the genetic code. Features of the genetic code of mitochondria indicate the possibility of its evolution in the process of historical development of living nature.
Among the triplets of the universal genetic code, three codons do not code for amino acids and determine the end of the synthesis of a given polypeptide molecule. These are the so-called "nonsens" codons (stop codons or terminators). These include: in DNA - ATT, ACT, ATC; in RNA - UAA, UGA, UAG.
The correspondence of nucleotides in a DNA molecule to the order of amino acids in a polypeptide molecule is called collinearity. Experimental confirmation of collinearity played a decisive role in deciphering the mechanism for the realization of hereditary information.
The meaning of the codons of the genetic code are given in table 8.1.
Table 8.1. Genetic code (mRNA codons for amino acids)
Using this table, mRNA codons can be used to determine amino acids. The first and third nucleotides are taken from the vertical columns located on the right and left, and the second - from the horizontal. The place where the conditional lines cross contains information about the corresponding amino acid. Note that the table lists mRNA triplets, not DNA triplets.
Structural - functional organization of the gene
Molecular biology of the gene
The modern understanding of the structure and function of the gene was formed in line with a new direction, which J. Watson called the molecular biology of the gene (1978)
An important stage in the study of the structural and functional organization of the gene was the work of S. Benzer in the late 1950s. They proved that a gene is a nucleotide sequence that can change as a result of recombinations and mutations. S. Benzer called the unit of recombination a recon, and the unit of mutation a muton. It has been experimentally established that the muton and recon correspond to one pair of nucleotides. S. Benzer called the unit of genetic function the cistron.
AT last years it became known that the gene has a complex internal structure, and its individual parts have different functions. In a gene, the nucleotide sequence of the gene can be distinguished, which determines the structure of the polypeptide. This sequence is called a cistron.
A cistron is a sequence of DNA nucleotides that determines a particular genetic function of a polypeptide chain. A gene may be represented by one or more cistrons. Complex genes containing several cistrons are called polycistronic.
Further development theory of the gene is associated with the identification of differences in the organization of the genetic material in organisms taxonomically distant from each other, which are pro- and eukaryotes.
Gene structure of prokaryotes
In prokaryotes, of which bacteria are typical representatives, most of the genes are represented by continuous informative DNA sections, all of which information is used in the synthesis of the polypeptide. In bacteria, genes occupy 80-90% of DNA. The main feature of prokaryotic genes is their association into groups or operons.
An operon is a group of successive structural genes controlled by a single regulatory region of DNA. All linked operon genes code for enzymes of the same metabolic pathway (eg lactose digestion). Such a common mRNA molecule is called polycistronic. Only a few genes in prokaryotes are individually transcribed. Their RNA is called monocistronic.
An operon-type organization allows bacteria to quickly switch metabolism from one substrate to another. Bacteria do not synthesize enzymes of a particular metabolic pathway in the absence of the required substrate, but are able to start synthesizing them when a substrate is available.
Structure of eukaryotic genes
Most eukaryotic genes (unlike prokaryotic genes) have a characteristic feature: they contain not only regions encoding the structure of the polypeptide - exons, but also non-coding regions - introns. Introns and exons alternate with each other, which gives the gene a discontinuous (mosaic) structure. The number of introns in genes varies from 2 to tens. The role of introns is not completely clear. It is believed that they are involved in the processes of recombination of genetic material, as well as in the regulation of expression (implementation of genetic information) of the gene.
Thanks to the exon-intron organization of genes, the prerequisites for alternative splicing are created. Alternative splicing is the process of “cutting out” different introns from the primary RNA transcript, as a result of which different proteins can be synthesized based on one gene. The phenomenon of alternative splicing occurs in mammals during the synthesis of various antibodies based on immunoglobulin genes.
Further study of the fine structure of the genetic material further complicated the clarity of the definition of the concept of "gene". Extensive regulatory regions have been found in the eukaryotic genome with various regions that can be located outside the transcription units at a distance of tens of thousands of base pairs. The structure of a eukaryotic gene, including transcribed and regulatory regions, can be represented as follows.
Fig 8.1. Structure of a eukaryotic gene
1 - enhancers; 2 - silencers; 3 – promoter; 4 - exons; 5 - introns; 6, exon regions encoding untranslated regions.
A promoter is a section of DNA for binding to RNA polymerase and the formation of a DNA-RNA polymerase complex to start RNA synthesis.
Enhancers are transcription enhancers.
Silencers are transcription attenuators.
Currently, the gene (cistron) is considered as a functionally indivisible unit of hereditary mastery, which determines the development of any trait or property of the organism. From the standpoint of molecular genetics, a gene is a section of DNA (in some viruses, RNA) that carries information about the primary structure of a polypeptide, a molecule of transport and ribosomal RNA.
Diploid human cells have approximately 32,000 gene pairs. Most of the genes in every cell are silent. The set of active genes depends on the type of tissue, the period of development of the organism, and the received external or internal signals. It can be said that in each cell its own chord of genes “sounds”, determining the spectrum of synthesized RNA, proteins and, accordingly, the properties of the cell.
Gene structure of viruses
Viruses have a gene structure that reflects the genetic structure of the host cell. Thus, bacteriophage genes are assembled into operons and do not have introns, while eukaryotic viruses have introns.
A characteristic feature of viral genomes is the phenomenon of "overlapping" genes ("gene within a gene"). In "overlapping" genes, each nucleotide belongs to one codon, but there are different frames for reading genetic information from the same nucleotide sequence. Thus, the phage φ X 174 has a segment of the DNA molecule, which is part of three genes at once. But the nucleotide sequences corresponding to these genes are read each in its own frame of reference. Therefore, it is impossible to talk about "overlapping" the code.
Such an organization of the genetic material ("gene within a gene") expands the information capabilities of a relatively small virus genome. The functioning of the genetic material of viruses occurs in different ways depending on the structure of the virus, but always with the help of the enzyme system of the host cell. Various ways organization of genes in viruses, pro- and eukaryotes are shown in Figure 8.2.
Functionally - genetic classification of genes
There are several classifications of genes. So, for example, allelic and non-allelic genes, lethal and semi-lethal, “housekeeping” genes, “luxury genes”, etc. are isolated.
Housekeeping Genes- a set of active genes necessary for the functioning of all cells of the body, regardless of the type of tissue, the period of development of the body. These genes encode enzymes for transcription, ATP synthesis, replication, DNA repair, etc.
"luxury" genes are selective. Their functioning is specific and depends on the type of tissue, the period of development of the organism, and the received external or internal signals.
Based on modern ideas about the gene as a functionally indivisible unit of hereditary material and the systemic organization of the genotype, all genes can be fundamentally divided into two groups: structural and regulatory.
Regulatory genes- encode the synthesis of specific proteins that affect the functioning of structural genes in such a way that the necessary proteins are synthesized in the cells of different tissue affiliation and in the required quantities.
Structural called genes that carry information about the primary structure of a protein, rRNA or tRNA. Protein-coding genes carry information about the amino acid sequence of certain polypeptides. From these DNA regions, mRNA is transcribed, which serves as a template for the synthesis of the primary structure of the protein.
rRNA genes(4 varieties are distinguished) contain information about the nucleotide sequence of ribosomal RNA and determine their synthesis.
tRNA genes(more than 30 varieties) carry information about the structure of transfer RNAs.
Structural genes, the functioning of which is closely related to specific sequences in the DNA molecule, called regulatory regions, are divided into:
independent genes;
Repetitive genes
gene clusters.
Independent genes are genes whose transcription is not associated with the transcription of other genes within the transcription unit. Their activity can be regulated by exogenous substances, such as hormones.
Repetitive genes present on the chromosome as repeats of the same gene. The ribosomal 5-S-RNA gene is repeated many hundreds of times, and the repeats are arranged in tandem, i.e., following closely one after another without gaps.
Gene clusters are groups of different structural genes with related functions localized in certain regions (loci) of the chromosome. Clusters are also often present in the chromosome in the form of repeats. For example, a cluster of histone genes is repeated in the human genome 10-20 times, forming a tandem group of repeats. (Fig. 8.3.)
Fig.8.3. Cluster of histone genes
With rare exceptions, clusters are transcribed as a whole, as one long pre-mRNA. So the pre-mRNA of the histone gene cluster contains information about all five histone proteins. This accelerates the synthesis of histone proteins, which are involved in the formation of the nucleosomal structure of chromatin.
There are also complex gene clusters that can code for long polypeptides with multiple enzymatic activities. For example, one of the NeuraSpora grassa genes encodes a polypeptide with a molecular weight of 150,000 daltons, which is responsible for 5 consecutive steps in the biosynthesis of aromatic amino acids. It is believed that polyfunctional proteins have several domains - conformationally limited semi-autonomous formations in the polypeptide chain that perform specific functions. The discovery of semifunctional proteins gave reason to believe that they are one of the mechanisms of the pleiotropic effect of one gene on the formation of several traits.
In the coding sequence of these genes, non-coding ones, called introns, can be wedged. In addition, between the genes there may be sections of spacer and satellite DNA (Fig. 8.4).
Fig.8.4. Structural organization of nucleotide sequences (genes) in DNA.
Spacer DNA is located between genes and is not always transcribed. Sometimes the region of such DNA between genes (the so-called spacer) contains some information related to the regulation of transcription, but it can also be simply short repetitive sequences of excess DNA, the role of which remains unclear.
Satellite DNA contains a large number of groups of repeating nucleotides that do not make sense and are not transcribed. This DNA is often located in the heterochromatin region of the centromeres of mitotic chromosomes. Single genes among satellite DNA have a regulatory and reinforcing effect on structural genes.
Micro- and minisatellite DNA are of great theoretical and practical interest for molecular biology and medical genetics.
microsatellite DNA- short tandem repeats of 2-6 (usually 2-4) nucleotides, which are called STR. The most common are nucleotide CA repeats. The number of repetitions can vary significantly for different people. Microsatellites are found predominantly in certain regions of DNA and are inherited according to the laws of Mendel. Children receive one chromosome from their mother, with a certain number of repeats, another from their father, with a different number of repeats. If such a cluster of microsatellites is located next to the gene responsible for a monogenic disease, or inside the gene, then a certain number of repeats along the length of the cluster can be a marker of the pathological gene. This feature is used in the indirect diagnosis of gene diseases.
Minisatellite DNA- tandem repeats of 15-100 nucleotides. They were called VNTR - tandem repeats variable in number. The length of these loci is also significantly variable in different people and can be a marker (label) of a pathological gene.
Micro- and macrosatellite DNA use:
1. For the diagnosis of gene diseases;
2. In forensic medical examination for personal identification;
3. To establish paternity and in other situations.
Along with structural and regulatory repeating sequences, the functions of which are unknown, migrating nucleotide sequences (transposons, mobile genes), as well as the so-called pseudogenes in eukaryotes, have been found.
Pseudogenes are non-functioning DNA sequences that are similar to functioning genes.
They probably occurred by duplication, and the copies became inactive as a result of mutations that violated any stages of expression.
According to one version, pseudogenes are an "evolutionary reserve"; in another way, they represent “dead ends of evolution”, side effect rearrangements of once functioning genes.
Transposons are structurally and genetically discrete DNA fragments that can move from one DNA molecule to another. First predicted by B. McClintock (Fig. 8) in the late 40s of the XX century based on genetic experiments on corn. Studying the nature of the color of corn grains, she made the assumption that there are so-called mobile ("jumping") genes that can move around the cell genome. Being next to the gene responsible for the pigmentation of corn grains, mobile genes block its work. Subsequently, transposons were identified in bacteria and it was found that they are responsible for the resistance of bacteria to various toxic compounds.
Rice. 8.5. Barbara McClintock was the first to predict the existence of mobile ("jumping") genes capable of moving around the genome of cells.
Mobile genetic elements perform the following functions:
1. encode proteins responsible for their movement and replication.
2. cause many hereditary changes in cells, as a result of which a new genetic material is formed.
3. leads to the formation of cancer cells.
4. integrating into different parts of chromosomes, they inactivate or enhance the expression of cellular genes,
5. is an important factor in biological evolution.
Current State of Gene Theory
Modern theories The gene is formed due to the transition of genetics to the molecular level of analysis and reflects the fine structural and functional organization of units of heredity. The main provisions of this theory are as follows:
1) gene (cistron) - a functional indivisible unit of hereditary material (DNA in organisms and RNA in some viruses), which determines the manifestation of a hereditary trait or property of an organism.
2) Most genes exist in the form of two or more alternative (mutually exclusive) variants of alleles. All alleles of a given gene are localized on the same chromosome in a certain section of it, which is called a locus.
3) Changes in the form of mutations and recombinations can occur inside the gene; the minimum sizes of a muton and a recon are equal to one pair of nucleotides.
4) There are structural and regulatory genes.
5) Structural genes carry information about the sequence of amino acids in a particular polypeptide and nucleotides in rRNA, tRNA
6) Regulatory genes control and direct the robot of structural genes.
7) The gene is not directly involved in protein synthesis, it is a template for synthesis various kinds RNAs that are directly involved in protein synthesis.
8) There is a correspondence (colinearity) between the arrangement of triplets of nucleotides in structural genes and the order of amino acids in the polypeptide molecule.
9) Most gene mutations do not manifest themselves in the phenotype, since DNA molecules are capable of repair (restoring their native structure)
10) The genotype is a system that consists of discrete units - genes.
11) The phenotypic manifestation of a gene depends on the genotypic environment in which the gene is located, the influence of factors of the external and internal environment.
“Gene”, “genome”, “chromosome” are words that are familiar to every schoolchild. But the idea of this issue is rather generalized, since deepening into the biochemical jungle requires special knowledge and a desire to understand all this. And it, if it is present at the level of curiosity, then quickly disappears under the weight of the presentation of the material. Let's try to understand the intricacies of hereditary information in a scientific polar form.
What is a gene?
A gene is the smallest structural and functional piece of information about heredity in living organisms. In essence, it represents small plot DNA, which contains knowledge about a certain sequence of amino acids for building a protein or functional RNA (from which a protein will also be synthesized). The gene determines those traits that will be inherited and passed on to descendants further along the genealogical chain. Some unicellular organisms have gene transfer that is not related to the reproduction of their own kind, it is called horizontal.
“On the shoulders” of genes lies a huge responsibility for how each cell and the organism as a whole will look and work. They govern our lives from conception to our very last breath.
The first scientific advance in the study of heredity was made by the Austrian monk Gregor Mendel, who in 1866 published his observations on the results of crossing peas. The hereditary material that he used clearly showed the patterns of transmission of traits, such as the color and shape of peas, as well as flowers. This monk formulated the laws that formed the beginning of genetics as a science. The inheritance of genes occurs because parents give their child half of all their chromosomes. Thus, the signs of mom and dad, mixing, form a new combination of already existing signs. Fortunately, there are more options than living creatures on the planet, and it is impossible to find two absolutely identical creatures.
Mendel showed that hereditary inclinations do not mix, but are transmitted from parents to descendants in the form of discrete (isolated) units. These units, represented in individuals by pairs (alleles), remain discrete and are passed on to subsequent generations in male and female gametes, each of which contains one unit from each pair. In 1909, the Danish botanist Johansen named these units genes. In 1912, Morgan, a geneticist from the United States of America, showed that they are in the chromosomes.
Since then, more than a century and a half have passed, and research has advanced further than Mendel could have imagined. At the moment, scientists have settled on the opinion that the information contained in the genes determines the growth, development and functions of living organisms. Or maybe even their death.
What is a chromosome? sex chromosomes
The totality of an individual's genes is called the genome. Naturally, the entire genome cannot be packed into a single DNA. The genome is divided into 46 pairs of DNA molecules. One pair of DNA molecules is called a chromosome. So it is precisely these chromosomes that a person has 46 pieces. Each chromosome carries a strictly defined set of genes, for example, the 18th chromosome contains genes encoding eye color, etc. Chromosomes differ from each other in length and shape. The most common forms are in the form of X or Y, but there are also others. A person has two chromosomes of the same shape, which are called paired (pairs). In connection with such differences, all paired chromosomes are numbered - there are 23 pairs. This means that there is a pair of chromosomes #1, pair #2, #3, and so on. Each gene responsible for a particular trait is located on the same chromosome. In modern manuals for specialists, the localization of the gene may be indicated, for example, as follows: chromosome 22, long arm.
What are the differences between chromosomes?
How else do chromosomes differ from each other? What does the term long arm mean? Let's take X-shaped chromosomes. The crossing of DNA strands can occur strictly in the middle (X), or it can occur not centrally. When such an intersection of DNA strands does not occur centrally, then relative to the point of intersection, some ends are longer, others, respectively, are shorter. Such long ends are commonly called the long arm of the chromosome, and short ends, respectively, the short arm. Y-shaped chromosomes are mostly occupied by long arms, and short ones are very small (they are not even indicated on the schematic image).
The size of the chromosomes fluctuates: the largest are the chromosomes of pairs No. 1 and No. 3, the smallest chromosomes of pairs No. 17, No. 19.
In addition to shapes and sizes, chromosomes differ in their functions. Out of 23 pairs, 22 pairs are somatic and 1 pair is sexual. What does it mean? Somatic chromosomes determine all the external signs of an individual, the characteristics of his behavioral reactions, hereditary psychotype, that is, all the features and characteristics of each individual person. A pair of sex chromosomes determines the sex of a person: male or female. There are two types of human sex chromosomes - X (X) and Y (Y). If they are combined as XX (X - X) - this is a woman, and if XY (X - Y) - we have a man in front of us.
Hereditary diseases and chromosome damage
However, there are "breakdowns" of the genome, then genetic diseases are detected in people. For example, when there are three chromosomes in 21 pairs of chromosomes instead of two, a person is born with Down syndrome.
There are many smaller "breakdowns" of the genetic material that do not lead to the onset of the disease, but, on the contrary, give good properties. All "breakdowns" of the genetic material are called mutations. Mutations that lead to disease or deterioration of the properties of the organism are considered negative, and mutations that lead to the formation of new beneficial properties are considered positive.
However, in relation to most of the diseases that people suffer today, it is not a disease that is inherited, but only a predisposition. For example, in the father of a child, sugar is absorbed slowly. This does not mean that the child will be born with diabetes but the child will have a predisposition. This means that if a child abuses sweets and flour products, then he will develop diabetes.
Today, the so-called predictive medicine is developing. As part of this medical practice, predispositions are identified in a person (based on the identification of the corresponding genes), and then recommendations are given to him - what diet to follow, how to properly alternate work and rest regimens so as not to get sick.
Sources of human diversity
Genes carry plans (or "drawings") of both common traits inherent in all people, and numerous individual differences. They determine the specific characteristics that distinguish a person from other living beings in such areas as the size and shape of the body, behavior and aging, at the same time determining those unique features that distinguish us from each other. Based on this, a blue-eyed blond weighing 80 kilograms with slightly protruding ears and an infectious smile, masterfully playing jazz on the trombone, can be considered one of a kind.
Human life begins with a single fertilized cell - the zygote. After the sperm enters the egg, the pronucleus of the egg, containing 23 chromosomes (literally, “painted bodies”), moves to its center in a few hours. Here it fuses with the sperm pronucleus, which also contains 23 chromosomes. Thus, the formed zygote contains 23 pairs of chromosomes (46 chromosomes in total), half from each of the parents, the amount necessary for a normal child to be born.
Zygote- the first cell of a human being, appearing as a result of - fertilization.
After the formation of a zygote, the process of cell division begins. As a result of the first crushing, two daughter cells appear, identical in their organization to the original zygote. In the course of further cell division and differentiation, each newly formed cell contains exactly the same number of chromosomes as any other, that is, 46. Each chromosome consists of many genes arranged in a chain. According to experts, the number of genes in one chromosome reaches tens of thousands, which means that in all 16 chromosomes there are about a million of them (Kelly, 1986). Nine months after conception, the zygote develops into a newborn baby with ten trillion cells organized into organs and systems. Upon reaching adulthood, there are already more than 300 trillion cells in his body. Each 13 of them contains the complete genetic code of the individual.
Genes are built from DNA (deoxyribonucleic acid) - a huge molecule consisting of carbon, hydrogen, oxygen, nitrogen and phosphorus atoms. "AT human body contains so many DNA molecules that if stretched out in a line, its length will exceed twice the distance from the Earth to the Moon by 20 thousand times” (Rugh & Shettles, 1971, p. 199). The structure of DNA resembles a long spiral staircase, the side railings of which are made of alternating phosphates and sugars, and the steps are made of four types of nitrogenous bases, connected in pairs in a regular way. The order of these paired bases changes, and it is these variations that cause one gene to differ from another. A single gene is part of this DNA ladder, which can be up to 2,000 steps long in its helix (Kelly, 1986).
Watson and Crick (1953) suggested that at the moment when the cell is ready to divide, the DNA helix unwinds, and two long chains diverge in different directions, separating from each other due to the breaking of bonds between paired nitrogenous bases. Then each chain, attracting to itself from the cage new material, synthesizes a second strand and forms a new molecule, changing the amount or structure of DNA. Mutations, or rearrangements, can occur from time to time in these long strands of nucleic acid. In most cases, such rearrangements lead to the death of the protein (and, consequently, the cell), but a small number of mutants survive and further affect the body.
Mutation- a change in the amount or structure of DNA, and hence the genetic code.
DNA contains the genetic code, or blueprint, that governs how an organism functions and develops. However, this plan, listing all the objects and the exact dates for their construction, is locked in the nucleus of the cell and is inaccessible to those of its elements that are assigned to build the body. RNA (ribonucleic acid) - a substance formed from and similar to DNA - acts as a messenger between the nucleus and the rest of the cell. If DNA is the "what" and "when", then RNA is the "how" of development. Shorter RNA chains, which are mirror images of sections of the DNA molecule, move freely inside the cell and serve as a catalyst for the formation of new tissue.
Viruses
About 1% of the human genome is occupied by built-in retrovirus genes (endogenous retroviruses). These genes usually do not benefit the host, but there are exceptions. So, about 43 million years ago, retroviral genes that served to build the envelope of the virus got into the genome of the ancestors of monkeys and humans. In humans and monkeys, these genes are involved in the work of the placenta.
Most retroviruses integrated into the genome of human ancestors over 25 million years ago. Among the younger human endogenous retroviruses, no useful ones have been found so far.
The concept of "gene" arose long before the emergence of science studying it. The Czech naturalist, the founder of modern genetics, Grgeor Mendel in 1865, analyzing experiments on crossing peas, came to the conclusion that the inheritance of traits is carried out by discrete particles, which he called "rudiments" or hereditary "factors". In 1868, Charles Darwin proposed the "temporary hypothesis" of pangenesis, according to which all cells of the body separate special particles, or gemmules, from themselves, and from them, in turn, sex cells are formed.
Then Hugo de Vries in 1889, 20 years after Charles Darwin, put forward his hypothesis of intracellular pangenesis and introduced the term "pangen" to refer to the material particles present in cells, which are responsible for quite specific individual hereditary properties characteristic of a given species. Charles Darwin's gemmules represented tissues and organs, de Vries' pangens corresponded to hereditary traits within the species.
In 1906, the English scientist W. Betson introduced the name of science - "genetics", and three years later, in 1909, the Danish scientist V. Johansen found it convenient to use only the second part of Hugo de Vries' term "gene" and replace it with the indefinite the concept of "rudiment", "determinant", "hereditary factor". At the same time, W. Johansen emphasized that "this term is completely unrelated to any hypotheses and has the advantage due to its brevity and ease with which it can be combined with other designations." He immediately formed the key derivative concept "genotype" to denote the hereditary constitution of gametes and zygotes as opposed to the phenotype. Thus, the concept of a gene as an elementary unit of heredity entered genetics. In the future, it was constantly refined thanks to numerous discoveries: the localization of genes in chromosomes was proved; it turned out that genes change as a result of mutations; the concept of alleles and their localization in the corresponding loci of homologous chromosomes was developed. In all genetic studies, the gene becomes the universally recognized unit of heredity.
Among geneticists there was a general belief in the indivisibility of the gene. They imagined the gene as a whole, as the last elementary unit of heredity. But already in the early 1930s, doubts arose that the gene was indivisible. The first signal in this respect was the discovery of multiple alleles, or a series of multiple alleles. It turned out that a single gene can change, giving a number of mutations associated with changes in a particular trait.
In some organisms, and above all in Drosophila, series of multiple alleles containing dozens of different mutations were discovered, and in cattle a series of alleles was found, including up to 80 mutations, i.e. as a result of mutations, 80 different states of one locus arose.
Since the beginning of the 1930s, a new stage in the study of the gene began. The laboratory of A. S. Serebrovsky was engaged in the development of its structure. The work of A. S. Serebrovsky, then N. P. Dubinin showed that the gene has a much more complex structure than previously thought.
Work was carried out to study the scute gene localized in the Drosophila sex chromosome. This gene determines the development of bristles on the fly's body. Various allelic mutations of the gene related to the underdevelopment of setae in certain specific areas of the body of Drosophila and varying degrees of reduction of setae. During the genetic analysis of these mutations, crossing them with each other, it turned out that in the heterozygote they behave partly as allelic genes, and partly as mutations of independent chromosome loci. Thus, the gene turned out to be a complex system in which mutations lead to changes in only its individual parts.
The name "multiple alleles" was replaced by the more successful "stepped alleles" and a hypothesis was formulated about the complex structure of the gene. The gene as a whole is called "basigene", and the mutated alleles are "transgenes".
Further development of the study of the structure of the gene is associated with the transition of genetic research methods from the chromosomal to the molecular level. Of great importance was the use in the work of geneticists until that time of little studied microorganisms: bacteria and even non-cellular forms - viruses. Of particular importance in these works was the study of bacteriophages from the "T" group, which infect Escherichia coli.
In the study of the nature of the gene, the work of Benzer and a number of other researchers carried out on bacteriophages and other objects was of particular importance. As a result of his work, Benzer introduced three new concepts:
- Previously, it was believed that crossing over could occur only between genes and, thus, a gene is the elementary unit of genetic recombination. However, it has been proven that recombinations also occur within the gene. The smallest unit of recombination is called the recon.
- Previously, the gene was considered the unit of mutation. However, it was found that changes in individual sections within a complex gene lead to a change in its function. The smallest unit capable of change was called the muton.
- The gene was considered a unit of function. Numerous studies have shown that the function of a gene can change depending on whether two mutant alleles of a complex gene are located on the same chromosome, and their normal alleles are in the homologous one (cis position), or the mutant alleles are located on two homologous chromosomes (transposition). The function unit is proposed to be called a cistron.
Parallel work of biochemists and geneticists showed that the smallest size of recon and muton is close to the size of one or several nucleotides. The cistron is homologous to the DNA segment that "encodes" the synthesis of a certain polypeptide, and contains a thousand or more nucleotides.
Functional genetic classification of genes
There are several classifications of genes (allelic and non-allelic, lethal and semi-lethal genes, etc.). The characteristics of the gene as a unit of the function of the hereditary material and the systemic principle of the organization of the genotype are reflected in the functional genetic classification of hereditary inclinations.
Structural called genes that control the development of specific traits. The product of the primary activity of a gene is either mRNA followed by a polypeptide, or rRNA and tRNA. Thus, structural genes contain information about the amino acid or nucleotide sequences of macromolecules. Structural genes of the three subgroups listed in the classification differ in the degree of pleiotropic action, and pronounced pleiotropy distinguishes the genes of the second and third subgroups, which are actively functioning in all cells. With their mutations, various and extensive disturbances in the development of the organism are observed. It is no coincidence that these genes are represented in the genotype in the amount of several tens of copies and are formed by moderately repetitive DNA sequences.
modulator genes the process of development of a trait or other genetic phenomena, such as the frequency of mutation of structural genes, are shifted in one direction or another. Some of the structural genes simultaneously perform the role of modulators (see the example of the "position effect"). Other modulator genes appear to lack any other genetic function. The appearance of such genes in evolution was of great importance. Due to the pleiotropic effect, many structural genes, along with the favorable and necessary for the normal development of the organism, also have undesirable effects that reduce the viability of the individual. Their adverse effect is weakened by modulator genes.
to regulatory include genes that coordinate the activity of structural genes that control the time of switching on of various loci in the process of individual development, depending on the cell type of a multicellular organism, as well as on the state of the environment.
Molecular biological concepts of the structure and functioning of genes
The ideas of molecular biology have now penetrated all branches of life science and determined the main trends in the development of theoretical, experimental and applied biology. Molecular biology evolved in the course of research into the physicochemical properties and biological role of nucleic acids and proteins. Its foundations were laid by works on the genetics of viruses and phages, the chemical nature of hereditary material, the mechanism of protein biosynthesis, the biological code, and the laws of ultrastructural organization of the cell. In this regard, molecular biology can be defined as a field of study of the regularities in the structure and changes of informational macromolecules and their participation in the fundamental processes of life.
In the field of genetics, molecular biology revealed the chemical nature of the substance of heredity, showed the physicochemical prerequisites for storing information in the cell and accurately copying it for transmission in a number of generations. The DNA of most biological objects (from mammals to bacteriophages) contains equal amounts of nucleotides with purine (adenine, guanine) and pyrimidine (thymine, cytosine) nitrogenous bases. This means that the association of DNA molecules into a double helix is carried out naturally, in accordance with the principle of complementarity - the adenyl nucleotide binds to the thymidyl nucleotide, and the guanyl nucleotide to the cytidyl nucleotide (Fig. 53). This design allows a semi-conservative way of DNA reduplication. At the same time, pairs A - T and G - C are arranged randomly along the DNA bispiral - A + T ≠ G + C. Therefore, by independently combining nucleotides that differ in nitrogenous base, it is possible to record a variety of information along the length of DNA molecules, the volume of which is proportional to the amount of nucleic acid in the cell.
According to molecular biological concepts, the gene as a unit of functioning of the hereditary material is characterized by a complex structure. Many details of the fine structure of the gene remain unknown. However, success modern science in this region are large enough to draw a basic model of a functioning gene.
The functional activity of a gene consists in the synthesis of RNA molecules on a DNA molecule or transcription (rewriting) of biological information in order to use it to form a protein. Transcription units (trancryptons) are larger than structural genes (Fig. 54). According to one of the models of transkipton in eukaryotic cells, it consists of a non-informative (acceptor) and an informative zone. The latter is formed by structural genes (cistrons), which are separated by DNA inserts - spacers that do not carry information about the amino acid sequences of proteins. The non-informative zone begins with the promoter gene (p), to which the enzyme RNA polymerase is attached, catalyzing the reaction of DNA-dependent formation of ribonucleic acids. This is followed by acceptor genes or operator genes (α 1, α 2, etc.), binding regulatory proteins (r 1, r 2, etc.), changes in which "open" the DNA of structural genes (s 1, s 2 etc.) to read information. One large RNA molecule is synthesized on the transcripton. Thanks to processing, its non-informative part is destroyed, and the informative part is split into fragments corresponding to individual structural genes. These fragments in the form of mRNA for the synthesis of specific polypeptides are transported into the cytoplasm. According to the above model, the transcript contains several structural genes. A group of these genes forms a functional unit and is called an operon. The functional unity of operons depends on the presence of operator genes that receive signals from the metabolic apparatus of the cytoplasm and activate structural genes.
The nature of the signals regulating the function of genes has been studied in prokaryotes. These are proteins whose synthesis is controlled by special regulator genes acting on operator genes. Activation of structural genes by means of gene regulators and operators is shown in the diagram (Fig. 55). Under normal conditions, the regulator gene is active and a repressor protein is synthesized in the cell, which binds to the operator gene and blocks it. This turns the entire operon out of the function.
The activation of the operon occurs if substrate molecules penetrate into the cytoplasm, the digestion of which requires the resumption of the synthesis of the corresponding enzyme. The substrate attaches to the repressor and deprives it of its ability to block the operator gene. In this case, the information from the structural gene is read and the required enzyme is formed. In the described example, the substrate plays the role of an inductor (stimulator) of the synthesis of "its" enzyme. The latter starts a biochemical reaction in which this substrate is used. As its concentration decreases, repressor molecules are released, which block the activity of the operator gene, which leads to the shutdown of the operon. In bacteria, a regulatory system has been described that converts active structural genes into an inactive state depending on the concentration in the cytoplasm of the end product of a certain biochemical reaction (Fig. 56). In this case, under the genetic control of the regulator gene, an inactive form of the repressor of the operator gene is formed. The repressor is activated as a result of interaction with the end product of this biochemical reaction and, by blocking the operator gene, turns off the corresponding operon. The synthesis of the enzyme catalyzing the formation of a substance that activates the repressor stops. The described systems of regulation of the function of structural genes are adaptive in nature. In the first example, the synthesis of the enzyme is triggered by the entry of the substrate of the corresponding reaction into the cell, in the second, the formation of the enzyme stops as soon as the need for the synthesis of a certain substance disappears.
The principles of regulation of gene activity in eukaryotes are apparently similar to those in bacteria. At the same time, the appearance of the nuclear envelope, the complication of gene interactions under conditions of diploidy, the need for a fine correlation of the genetic functions of individual cells of a multicellular organism, entailed, during the transition to the eukaryotic type of cellular organization, the complication of regulatory genetic mechanisms, the genetic, biochemical and cybernetic foundations of which are still largely unknown. clarified. It can also be assumed that the number of operator genes has increased in evolution. The transcription inducers of many eukaryotic structural genes are hormones. It is assumed that there are integrator genes that simultaneously turn on “gene batteries” in response to a stimulus. The genetic system of higher organisms is apparently distinguished by a great flexibility of reactions to the action of non-genetic factors. To support this assumption, consider a number of factors. Thus, some structural animal genes are not continuous sequences of codons, but are composed of fragments that are interrupted by non-informative DNA sections. The mouse hemoglobin P-polypeptide gene, for example, is interrupted by a 550 bp insertion. The region corresponding to this insert is absent in the mature globin mRNA, which indicates its destruction during the processing of the primary transcribed RNA with the reunification of information fragments of the mRNA. Information sections of such genes are called exons, "silent" - introns, and the process of reunification of informational fragments of mRNA - splicing (fusion). The amount of DNA in the region of introns is 5-10 times higher than in the region of exons. It is assumed that splicing serves as a mechanism for the formation of some genes at the time of their functional activity, i.e., at the 1st level of mRNA.
There are also known "wandering" structural genes, the position of which in the chromosome changes depending on the phase of the life cycle. Thus, "heavy" and "light" immunoglobulin polypeptides consist of constant (C) and variable (Y) regions, the synthesis of which is controlled by linked but different genes. In mature plasma cells, these genes are separated by a 1000 bp long non-transcribed insert. In embryonic cells, the named insert is many times longer. Thus, in the process of cell differentiation, the mutual arrangement of genes changes. The study of the mechanisms of regulation of gene activity and gene interactions in eukaryotes is an important area of modern molecular biology and genetics.
Gene properties
The gene as a unit of functioning of the hereditary material has a number of properties.
- Specificity - a unique nucleotide sequence for each structural gene, i.e. each gene codes for its own trait;
- Integrity - as a functional unit (programming of protein synthesis), the gene is indivisible;
- Discreteness - the gene contains subunits: muton - a subunit responsible for mutation, recon - responsible for recombination. Their minimum value is a pair of nucleotides;
- Stability - a gene, as a discrete unit of heredity, is distinguished by stability (constancy) - in the absence of a mutation, it is transmitted in a number of generations unchanged. The frequency of spontaneous mutation of one gene is approximately 1·10 -5 per generation.
- Lability - the stability of genes is not absolute, they can change, mutate;
- Pleiotropy - the multiple effect of a single gene (one gene is responsible for several traits);
An example of the pleiotropic effect of a gene in humans is Marfan's syndrome. Although this hereditary disease depends on the presence of one altered gene in the genotype, it is characterized in typical cases by a triad of signs: subluxation of the lens of the eye, aortic aneurysm, changes in the musculoskeletal system in the form of "spider fingers", deformed chest, high arch of the foot. All of the above are complex. Apparently, they are based on the same defect in the development of connective tissue.
Since the product of the gene function is most often a protein-enzyme, the severity of the pleiotropic effect depends on the prevalence of the biochemical reaction in the body, which is catalyzed by the enzyme synthesized under the genetic control of this gene. The prevalence of lesions in the body in the case of a hereditary disease is the greater, the more pronounced the pleiotropic effect of the altered gene.
A gene that is present in the genotype in the amount necessary for manifestation (1 allele for dominant traits and 2 alleles for recessive traits) can manifest itself as a trait to varying degrees in different organisms (expressivity) or not manifest itself at all (penetrance). Expressivity and penetrance are determined by environmental factors (impact of environmental conditions - modification variability) and the influence of other genes of the genotype (combinative variability).
- Expressivity - the degree of expression of a gene in a trait or the degree of phenotypic manifestation of a gene.
For example, alleles of blood groups AB0 in humans have constant expressivity (always appear at 100%), and alleles that determine eye color have variable expressivity. A recessive mutation that reduces the number of eye facets in Drosophila reduces the number of facets in different individuals in different ways, up to their complete absence.
- Penetrance - the frequency of phenotypic manifestation of a trait in the presence of the corresponding gene (the ratio (in percent) of the number of individuals with this trait to the number of individuals with this gene);
For example, the penetrance of congenital hip dislocation in humans is 25%, i.e. only 1/4 of recessive homozygotes suffer from the disease. Medico-genetic significance of penetrance: a healthy person, in which one of the parents suffers from a disease with incomplete penetrance, can have an unexpressed mutant gene and pass it on to children.
discrete unit heredity in higher organisms is a gene. The totality of all genes of a certain biological species is defined by the term genome (sometimes this term refers to the complete genetic system of a single cell or a particular organism). A gene in its most practical sense is a strictly defined section of a DNA molecule, the sequence of which contains all the information necessary for the synthesis of a protein or RNA molecule. Genetic information is encrypted by means of a genetic code universal for all living organisms, which is a set of nucleotide triplets - codons. Each such triplet (i.e., each sequence of 3 nucleotides) encodes the synthesis of one, strictly defined amino acid in the protein.
Reading codons in process the transfer of genetic information occurs sequentially (the principle of linearity of the genetic code), and any nucleotide can be part of only one codon (the principle of non-overlapping of the genetic code). The genetic code is degenerate, i.e. allows each of the 20 amino acids to be encoded by several possible combinations of triplets (there can be 64 such combinations in total). Deciphering the exact nucleotide sequence of a certain informational region of the gene makes it possible to uniquely identify the amino acid sequence in the composition of the corresponding polypeptide region of the protein and its size. The complete human haploid genome (i.e., encoded by one semantic strand of DNA) includes approximately 30,000-40,000 genes.
Human and other higher genes organisms have an extremely complex structural and functional organization and contain nucleotide sites that differ in their biological role. Some of them (exons) are relatively short, they are coding sequences and determine the amino acid composition of proteins; other parts of the gene (introns) are usually much longer and do not carry direct information load. The final role of introns has not yet been established; it is assumed that they may be related to the regulation of gene expression and the control of subtle mechanisms of "reading" genetic information. The genes also include special regulatory regions (promoters, enhancers, various signal sequences) that provide the initiation, intensity, and a certain temporal sequence of nucleotide synthesis processes on the DNA template, as well as the modification of intermediate polynucleotide products.
According to indicative estimated, the actual coding DNA sequences make up no more than 3-10% of the entire human genome.
In any cell organism contains a complete set of genes, but only a small part of them is functionally active in each specific tissue, i.e. expressed. Gene expression is understood as the implementation of the genetic information recorded in it, leading to the synthesis of the primary molecular products of the gene - RNA and protein. It is the temporal and tissue selectivity of gene expression that determines the specifics of the differentiation and functioning of various organs, tissues and cells of the body in ontogeny.