Gene mutations: examples, causes, types, mechanisms. Mutational variability. Methods for classifying mutations Mutational variability briefly

Researchers have long noticed that organisms sometimes experience sudden, not caused by crossing, changes in traits that are inherited. The word mutation is translated from Latin (mutatio) and means change. These changes occur in all species and are of great importance as a factor in evolution.

Mutation theory

Mutational variability was studied in the late 19th and early 20th centuries by Hugo de Vries. He observed the plant donkey tree and noticed that it develops new properties relatively often. De Vries coined the term “mutation” to refer to these changes.

At first it was not known which cell structures were rearranged due to mutational variability. But later it was discovered that large forms of aspen grass have 28 chromosomes, while ordinary ones have only 14.

It became clear that mutations are changes in the genotype and are therefore a type of hereditary variability.

The consolidation of changes in the offspring due to mutations is the main difference from modification variability, in which changes appear only in the phenotype.

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In addition, in the case of mutational variability, the reaction norm, i.e., the limit of manifestation of the trait, significantly expands. As a result, harmful mutations occur more often, causing changes that are incompatible with life.

Mutations can also be beneficial and neutral.

Causes of mutations

The factor that causes mutations is called a mutagen. An organism that has a mutation is a mutant.

Mutagens include:

• radiation (including natural);
• some chemicals;
• temperature fluctuations.

Types of mutations

There are three types of mutations:

• genetic;
• chromosomal;
• genomic.

Genetic

Gene mutations cause disturbances in protein synthesis because they change or make codons meaningless.
With these mutations occurs:

• replacement of nitrogenous bases in DNA;
• loss or insertion of a nitrogenous base into DNA.

Rice. 1. Gene mutations

Chromosomal

This type of mutation includes:

• loss of a chromosome section;
• duplication of a chromosome fragment;
• movement of chromosome fragments along their length;
• transition of a fragment of one chromosome to another;
• rotation of a region in a chromosome

Rice. 2. Chromosomal mutations

As a rule, such changes reduce the viability and fertility of individuals.

All felines have 36 chromosomes. Differences between species in the genotype are due to rotations of chromosome sections.

Genomic

Genomic mutations cause a multiple increase in the number of chromosomes. Such mutants are called polyploids and are widely used in agriculture because they are more productive.

Many varieties of grains that we eat are polyploids.

In the Novosibirsk and Nizhny Novgorod regions of Russia, triploid (3n) aspen grows, which differs from the usual growth rate, large size, as well as the strength of the wood and its resistance to fungi.

Rice. 3. Polyploids

The meaning of mutations

The ability to undergo mutational variability is a natural property of any species. Mutations are sources of hereditary variability, an important factor in evolution.

Beneficial manifestations of mutations are especially often observed in plants. According to some geneticists, most plant species are polyploids.

Humans use mutations to control agricultural pests and develop productive breeds and varieties.

Many varieties of cultivated plants are examples of mutational variability purposefully carried out by humans.

Some hereditary diseases are the result of mutations.

What have we learned?

While studying genetics in 10th grade, we characterized mutational variability. Mutations occur in different species under the influence of mutagens. Changes in traits sometimes give an advantage to a mutant. Mutational variability, as one of the types of hereditary variability, is a factor in evolution.

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Variability is the ability of organisms to change their characteristics and properties, which is manifested in the diversity of individuals within a species.

There are 2 forms of variability:

non-hereditary (phenotypic) or modification

hereditary (genotypic)

Modification variability is the variability of the phenotype that

is the response of a specific genotype to changing environmental conditions. They are not inherited and arise as a reaction of the body, that is, they represent an adaptation.

Modification variability is characterized by the following features:

is of a group nature

is reversible

environmental influences can change the phenotypic manifestation of a trait. The reaction norm is the limit of modification variability of a trait determined by the genotype. For example, such quantitative characteristics as the body weight of an animal and the size of plant leaves vary quite widely, that is, they have a wide reaction rate. The sizes of the heart and brain vary within narrow limits, that is, they have a narrow reaction rate. The reaction norm is expressed as a variation series.

has transitional forms.

A variation curve is a graphical expression of modification variability, reflecting the scope of variation and the frequency of occurrence of individual variants.

Genotypic variability is divided into:

combinative

mutational

Combinative variability- a type of hereditary variability caused by various recombinations of existing genes and chromosomes. It is not accompanied by changes in the structure of genes and chromosomes.

Its source is: - recombination of genes as a result of crossing over;

Recombination of chromosomes during meiosis; - a combination of chromosomes as a result of the fusion of germ cells during fertilization.

Mutational variability is a type of hereditary variability caused by the manifestation of various changes in the structure of genes, chromosomes or genome.

COMPARATIVE CHARACTERISTICS OF FORMS OF VARIATION

Mutational variability

Mutations are the basis of mutational variability.

Mutations- These are sudden, natural or artificially caused changes in the genetic material, leading to changes in the characteristics of the organism. The foundations of the doctrine of mutations were laid by Hugo de Vries in 1901.

Mutations are characterized by a number of properties:

They appear suddenly, without transitional forms;

These are qualitative changes, do not form continuous series and are not grouped around an average value;

They have a non-directional effect - under the influence of the same mutagenic factor, any part of the structure carrying genetic information;

Passed on from generation to generation.

Mutagens are factors that cause mutations. Divided into three categories:

physical (radiation, electromagnetic radiation, pressure, temperature, etc.).

chemical (salts of heavy metals, pesticides, phenols, alcohols, enzymes, narcotic substances, medications, food preservatives, etc.)

CLASSIFICATION OF MUTATIONS:

By level of occurrence

1. chromosomal;

   genomic

By type of allelic interactions

dominant;

recessive;

Almost any change in the structure or number of chromosomes, in which the cell retains the ability to reproduce itself, causes a hereditary change in the characteristics of the organism. According to the nature of the genome change, i.e. sets of genes contained in a haploid set of chromosomes, gene, chromosomal and genomic mutations are distinguished. hereditary mutant chromosomal genetic

Gene mutations are molecular changes in the structure of DNA that are not visible in a light microscope. Gene mutations include any changes in the molecular structure of DNA, regardless of their location and effect on viability. Some mutations have no effect on the structure or function of the corresponding protein. Another (large) part of gene mutations leads to the synthesis of a defective protein that is unable to perform its inherent function.

Based on the type of molecular changes, there are:

Deletions (from the Latin deletio - destruction), i.e. loss of a DNA segment from one nucleotide to a gene;

Duplications (from the Latin duplicatio doubling), i.e. duplication or reduplication of a DNA segment from one nucleotide to entire genes;

Inversions (from the Latin inversio - inversion), i.e. a 180-degree rotation of a DNA segment ranging in size from two nucleotides to a fragment including several genes;

Insertions (from the Latin insertio - attachment), i.e. insertion of DNA fragments ranging in size from one nucleotide to an entire gene.

It is gene mutations that cause the development of most hereditary forms of pathology. Diseases caused by such mutations are called genetic or monogenic diseases, i.e. diseases the development of which is determined by a mutation of one gene.

The effects of gene mutations are extremely varied. Most of them do not appear phenotypically because they are recessive. This is very important for the existence of the species, since most newly occurring mutations are harmful. However, their recessive nature allows them to persist for a long time in individuals of the species in a heterozygous state without harm to the body and manifest themselves in the future upon transition to a homozygous state.

Currently, there are more than 4,500 monogenic diseases. The most common of them are: cystic fibrosis, phenylketonuria, Duchenne-Becker myopathies and a number of other diseases. Clinically, they manifest themselves as signs of metabolic disorders (metabolism) in the body.

At the same time, there are a number of cases where a change in only one base in a certain gene has a noticeable effect on the phenotype. One example is the genetic abnormality of sickle cell anemia. The recessive allele, which causes this hereditary disease in the homozygous state, is expressed in the replacement of just one amino acid residue in the B-chain of the hemoglobin molecule (glutamic acid? ?> valine). This leads to the fact that in the blood red blood cells with such hemoglobin are deformed (from rounded ones become sickle-shaped) and quickly collapse. At the same time, acute anemia develops and a decrease in the amount of oxygen carried by the blood is observed. Anemia causes physical weakness, disturbances in the functioning of the heart and kidneys, and can lead to early death in people homozygous for the mutant allele.

Chromosomal mutations are the causes of chromosomal diseases.

Chromosomal mutations are structural changes to individual chromosomes, usually visible under a light microscope. A chromosomal mutation involves a large number (from tens to several hundreds) of genes, which leads to a change in the normal diploid set. Although chromosomal aberrations generally do not change the DNA sequence of specific genes, changes in the copy number of genes in the genome lead to genetic imbalance due to a lack or excess of genetic material. There are two large groups of chromosomal mutations: intrachromosomal and interchromosomal (see Fig. 2).

Intrachromosomal mutations are aberrations within one chromosome (see Fig. 3). These include:

Deletions are the loss of one of the chromosome sections, internal or terminal. This can cause a disruption of embryogenesis and the formation of multiple developmental anomalies (for example, a deletion in the region of the short arm of the 5th chromosome, designated 5p-, leads to underdevelopment of the larynx, heart defects, mental retardation. This symptom complex is known as the “cry of the cat” syndrome, because in sick children, due to an anomaly of the larynx, crying resembles a cat’s meow);

Inversions. As a result of two points of chromosome breaks, the resulting fragment is inserted into its original place after a rotation of 180 degrees. As a result, only the order of the genes is disrupted;

Duplications are the doubling (or multiplication) of any part of a chromosome (for example, trisomy on the short arm of chromosome 9 causes multiple defects, including microcephaly, delayed physical, mental and intellectual development).

Rice. 2.

Interchromosomal mutations, or rearrangement mutations, are the exchange of fragments between non-homologous chromosomes. Such mutations are called translocations (from the Latin trans - for, through and locus - place). This:

Reciprocal translocation - two chromosomes exchange their fragments;

Non-reciprocal translocation - a fragment of one chromosome is transported to another;

? “centric” fusion (Robertsonian translocation) is the joining of two acrocentric chromosomes in the region of their centromeres with the loss of short arms.

When chromatids are transversely broken through centromeres, “sister” chromatids become “mirror” arms of two different chromosomes containing the same sets of genes. Such chromosomes are called isochromosomes.



Rice. 3.

Translocations and inversions, which are balanced chromosomal rearrangements, do not have phenotypic manifestations, but as a result of segregation of rearranged chromosomes in meiosis, they can form unbalanced gametes, which will lead to the emergence of offspring with chromosomal abnormalities.

Genomic mutations, like chromosomal ones, are the causes of chromosomal diseases.

Genomic mutations include aneuploidies and changes in the ploidy of structurally unchanged chromosomes. Genomic mutations are detected by cytogenetic methods.

Aneuploidy is a change (decrease - monosomy, increase - trisomy) in the number of chromosomes in a diploid set, not a multiple of the haploid one (2n+1, 2n-1, etc.).

Polyploidy is an increase in the number of sets of chromosomes, a multiple of the haploid one (3n, 4n, 5n, etc.).

In humans, polyploidy, as well as most aneuploidies, are lethal mutations.

The most common genomic mutations include:

Trisomy - the presence of three homologous chromosomes in the karyotype (for example, the 21st pair in Down syndrome, the 18th pair in Edwards syndrome, the 13th pair in Patau syndrome; for sex chromosomes: XXX, XXY, XYY);

Monosomy is the presence of only one of two homologous chromosomes. With monosomy for any of the autosomes, normal development of the embryo is not possible. The only monosomy in humans that is compatible with life - monosomy on the X chromosome - leads to Shereshevsky-Turner syndrome (45,X).

The reason leading to aneuploidy is the non-disjunction of chromosomes during cell division during the formation of germ cells or the loss of chromosomes as a result of anaphase lag, when during movement to the pole one of the homologous chromosomes may lag behind other non-homologous chromosomes. The term nondisjunction means the absence of separation of chromosomes or chromatids in meiosis or mitosis.

Chromosome nondisjunction most often occurs during meiosis. The chromosomes, which normally should divide during meiosis, remain joined together and move to one pole of the cell in anaphase, thus producing two gametes, one of which has an extra chromosome, and the other does not have this chromosome. When a gamete with a normal set of chromosomes is fertilized by a gamete with an extra chromosome, trisomy occurs (i.e., there are three homologous chromosomes in the cell); when a gamete without one chromosome is fertilized, a zygote with monosomy occurs. If a monosomic zygote is formed on any autosomal chromosome, then the development of the organism stops at the earliest stages of development.

According to the type of inheritance they distinguish dominant And recessive mutations. Some researchers identify semi-dominant and codominant mutations. Dominant mutations are characterized by a direct effect on the body, semi-dominant mutations mean that the heterozygous form is intermediate in phenotype between the AA and aa forms, and codominant mutations are characterized by the fact that heterozygotes A 1 A 2 show signs of both alleles. Recessive mutations do not appear in heterozygotes.

If a dominant mutation occurs in gametes, its effects are expressed directly in the offspring. Many mutations in humans are dominant. They are common in animals and plants. For example, a generative dominant mutation gave rise to the Ancona breed of short-legged sheep.

An example of a semi-dominant mutation is the mutational formation of the heterozygous form Aa, intermediate in phenotype between the organisms AA and aa. This occurs in the case of biochemical traits when the contribution of both alleles to the trait is the same.

An example of a codominant mutation is the alleles I A and I B, which determine blood group IV.

In the case of recessive mutations, their effects are hidden in diploids. They appear only in the homozygous state. An example is recessive mutations that determine human gene diseases.

Thus, the main factors in determining the probability of manifestation of a mutant allele in an organism and population are not only the stage of the reproductive cycle, but also the dominance of the mutant allele.

Direct mutations? These are mutations that inactivate wild-type genes, i.e. mutations that change the information encoded in DNA in a direct way, resulting in a change from the original (wild) type organism to a mutant type organism.

Back mutations represent reversions to the original (wild) types from mutants. These reversions are of two types. Some of the reversions are caused by repeated mutations of a similar site or locus with restoration of the original phenotype and are called true reverse mutations. Other reversions are mutations in some other gene that change the expression of the mutant gene towards the original type, i.e. the damage in the mutant gene remains, but it seems to restore its function, resulting in the restoration of the phenotype. Such restoration (full or partial) of the phenotype despite the preservation of the original genetic damage (mutation) is called suppression, and such reverse mutations are called suppressor (extragenic). As a rule, suppression occurs as a result of mutations in genes encoding the synthesis of tRNA and ribosomes.

In general, suppression can be:

? intragenic? when a second mutation in an already affected gene changes a codon defective as a result of a direct mutation in such a way that an amino acid is inserted into the polypeptide that can restore the functional activity of this protein. Moreover, this amino acid does not correspond to the original one (before the first mutation occurred), i.e. no true reversibility observed;

? introduced? when the structure of tRNA changes, as a result of which the mutant tRNA includes in the synthesized polypeptide another amino acid instead of that encoded by a defective triplet (resulting from a direct mutation).

Compensation for the effect of mutagens due to phenotypic suppression is not excluded. It can be expected when the cell is exposed to a factor that increases the likelihood of errors in reading mRNA during translation (for example, some antibiotics). Such errors can lead to the substitution of the wrong amino acid, which, however, restores the protein function impaired as a result of direct mutation.

Mutations, in addition to their qualitative properties, are also characterized by the method of their occurrence. Spontaneous(random) - mutations that occur under normal living conditions. They are the result of natural processes occurring in cells, arising in the natural radioactive background of the Earth in the form of cosmic radiation, radioactive elements on the surface of the Earth, radionuclides incorporated into the cells of organisms that cause these mutations or as a result of DNA replication errors. Spontaneous mutations occur in humans in somatic and generative tissues. The method for determining spontaneous mutations is based on the fact that children develop a dominant trait, although their parents do not have it. A Danish study showed that approximately one in 24,000 gametes carries a dominant mutation. The frequency of spontaneous mutation in each species is genetically determined and maintained at a certain level.

Induced mutagenesis is the artificial production of mutations using mutagens of various natures. There are physical, chemical and biological mutagenic factors. Most of these factors either directly react with nitrogenous bases in DNA molecules or are included in nucleotide sequences. The frequency of induced mutations is determined by comparing cells or populations of organisms treated and untreated with the mutagen. If the frequency of a mutation in a population increases 100 times as a result of treatment with a mutagen, then it is believed that only one mutant in the population will be spontaneous, the rest will be induced. Research on the creation of methods for the targeted effect of various mutagens on specific genes is of practical importance for the selection of plants, animals and microorganisms.

Based on the type of cells in which mutations occur, generative and somatic mutations are distinguished (see Fig. 4).

Generative mutations occur in the cells of the reproductive primordium and in the germ cells. If a mutation (generative) occurs in genital cells, then several gametes can receive the mutant gene at once, which will increase the potential ability of several individuals (individuals) to inherit this mutation in the offspring. If a mutation occurs in a gamete, then probably only one individual (individual) in the offspring will receive this gene. The frequency of mutations in germ cells is influenced by the age of the organism.




Rice. 4.

Somatic mutations occur in the somatic cells of organisms. In animals and humans, mutational changes will persist only in these cells. But in plants, due to their ability to reproduce vegetatively, the mutation can spread beyond the somatic tissues. For example, the famous winter apple variety “Delicious” originates from a mutation in a somatic cell, which, as a result of division, led to the formation of a branch that had the characteristics of a mutant type. This was followed by vegetative propagation, which made it possible to obtain plants with the properties of this variety.

The classification of mutations depending on their phenotypic effect was first proposed in 1932 by G. Möller. According to the classification, the following were identified:

Amorphous mutations. This is a condition in which the trait controlled by the pathological allele is not expressed because the pathological allele is inactive compared to the normal allele. Such mutations include the albinism gene and about 3,000 autosomal recessive diseases;

Antimorphic mutations. In this case, the value of the trait controlled by the pathological allele is opposite to the value of the trait controlled by the normal allele. Such mutations include genes of about 5-6 thousand autosomal dominant diseases;

Hypermorphic mutations. In the case of such a mutation, the trait controlled by the pathological allele is more pronounced than the trait controlled by the normal allele. Example? heterozygous carriers of genes for diseases of genome instability. Their number is about 3% of the world's population, and the number of diseases themselves reaches 100 nosologies. Among these diseases: Fanconi anemia, ataxia telangiectasia, xeroderma pigmentosum, Bloom's syndrome, progeroid syndromes, many forms of cancer, etc. Moreover, the frequency of cancer in heterozygous carriers of the genes for these diseases is 3-5 times higher than normal, and in patients themselves ( homozygotes for these genes), the incidence of cancer is tens of times higher than normal.

Hypomorphic mutations. This is a condition in which the expression of a trait controlled by a pathological allele is weakened compared to the trait controlled by a normal allele. Such mutations include mutations in pigment synthesis genes (1q31; 6p21.2; 7p15-q13; 8q12.1; 17p13.3; 17q25; 19q13; Xp21.2; Xp21.3; Xp22), as well as more than 3000 forms of autosomal recessive diseases.

Neomorphic mutations. Such a mutation is said to occur when the trait controlled by the pathological allele is of a different (new) quality compared to the trait controlled by the normal allele. Example: synthesis of new immunoglobulins in response to the penetration of foreign antigens into the body.

Speaking about the enduring significance of G. Möller’s classification, it should be noted that 60 years after its publication, the phenotypic effects of point mutations were divided into different classes depending on the effect they had on the structure of the protein product of the gene and/or its level of expression.

The genomes of living organisms are relatively stable, which is necessary to preserve the species structure and continuity of development. In order to maintain stability in the cell, various repair systems operate to correct violations in the DNA structure. However, if changes in DNA structure were not maintained at all, species would not be able to adapt to changing environmental conditions and evolve. In creating evolutionary potential, i.e. the required level of hereditary variability, the main role belongs to mutations.

The term “ mutation“G. de Vries in his classic work “Mutation Theory” (1901-1903) outlined the phenomenon of spasmodic, intermittent changes in a trait. He noted a number features of mutational variability:

• a mutation is a qualitatively new state of a trait;
• mutant forms are constant;
• the same mutations can occur repeatedly;
• mutations can be beneficial or harmful;
• detection of mutations depends on the number of individuals analyzed.

The basis for the occurrence of a mutation is a change in the structure of DNA or chromosomes, so mutations are inherited in subsequent generations. Mutational variability is universal; it occurs in all animals, higher and lower plants, bacteria and viruses.

Conventionally, the mutation process is divided into spontaneous and induced. The first occurs under the influence of natural factors (external or internal), the second - with a targeted effect on the cell. The frequency of spontaneous mutagenesis is very low. In humans, it lies in the range of 10 -5 - 10 -3 per gene per generation. In terms of the genome, this means that each of us has, on average, one gene that our parents did not have.

Most mutations are recessive, which is very important because... mutations violate the established norm (wild type) and are therefore harmful. However, the recessive nature of mutant alleles allows them to persist in the population for a long time in a heterozygous state and manifest themselves as a result of combinative variability. If the resulting mutation has a beneficial effect on the development of the organism, it will be preserved by natural selection and spread among individuals of the population.

According to the nature of the action of the mutant gene mutations are divided into 3 types:

• morphological,
• physiological,
• biochemical.

Morphological mutations change the formation of organs and growth processes in animals and plants. An example of this type of change is mutations in eye color, wing shape, body color, and shape of bristles in Drosophila; short-legged in sheep, dwarfism in plants, short-toed (brachydactyly) in humans, etc.

Physiological mutations usually reduce the viability of individuals, among them there are many lethal and semi-lethal mutations. Examples of physiological mutations are respiratory mutations in yeast, chlorophyll mutations in plants, and hemophilia in humans.

TO biochemical mutations include those that inhibit or disrupt the synthesis of certain chemicals, usually as a result of the lack of a necessary enzyme. This type includes auxotrophic mutations of bacteria, which determine the inability of the cell to synthesize any substance (for example, an amino acid). Such organisms are able to live only in the presence of this substance in the environment. In humans, the result of a biochemical mutation is a severe hereditary disease - phenylketonuria, caused by the absence of the enzyme that synthesizes tyrosine from phenylalanine, as a result of which phenylalanine accumulates in the blood. If the presence of this defect is not established in time and phenylalanine is not excluded from the diet of newborns, then the body faces death due to severe impairment of brain development.

Mutations may be generative And somatic. The former arise in the germ cells, the latter in the cells of the body. Their evolutionary value is different and is associated with the method of reproduction.

Generative mutations can occur at different stages of germ cell development. The earlier they arise, the greater the number of gametes that will carry them, and, therefore, the chance of their transmission to offspring will increase. A similar situation occurs in the case of a somatic mutation. The earlier it occurs, the more cells will carry it. Individuals with altered areas of the body are called mosaics, or chimeras. For example, in Drosophila, mosaicism in eye color is observed: against the background of red color, white spots (facets devoid of pigment) appear as a result of mutation.

In organisms that reproduce only sexually, somatic mutations do not represent any value either for evolution or for selection, because they are not inherited. In plants that can reproduce vegetatively, somatic mutations can become material for selection. For example, bud mutations that produce altered shoots (sports). From such a sport I.V. Michurin, using the grafting method, obtained a new variety of apple tree, Antonovka 600-gram.

Mutations are diverse not only in their phenotypic manifestation, but also in the changes that occur in the genotype. There are mutations genetic, chromosomal And genomic.

Gene mutations

Gene mutations change the structure of individual genes. Among them, a significant part are point mutations, in which the change affects one pair of nucleotides. Most often, point mutations involve a substitution of nucleotides. There are two types of such mutations: transitions and transversions. During transitions in a nucleotide pair, purine is replaced by purine or pyrimidine by pyrimidine, i.e. the spatial orientation of the bases does not change. In transversions, a purine is replaced by a pyrimidine or a pyrimidine by a purine, which changes the spatial orientation of the bases.

By the nature of the influence of base substitution on the structure of the protein encoded by the gene There are three classes of mutations: missence mutations, nonsence mutations and samesence mutations.

Missence mutations change the meaning of the codon, which leads to the appearance of one incorrect amino acid in the protein. This can have very serious consequences. For example, a severe hereditary disease - sickle cell anemia, a form of anemia, is caused by the replacement of a single amino acid in one of the hemoglobin chains.

Nonsense mutation is the appearance (as a result of the replacement of one base) of a terminator codon within a gene. If the translation ambiguity system is not turned on (see above), the process of protein synthesis will be interrupted, and the gene will be able to synthesize only a fragment of the polypeptide (abortive protein).

At samesense mutations substitution of one base results in the appearance of a synonym codon. In this case, there is no change in the genetic code, and normal protein is synthesized.

In addition to nucleotide substitutions, point mutations can be caused by the insertion or deletion of a single nucleotide pair. These violations lead to a change in the reading frame; accordingly, the genetic code changes and an altered protein is synthesized.

Gene mutations include duplication and loss of small sections of the gene, as well as insertions- insertions of additional genetic material, the source of which is most often mobile genetic elements. Gene mutations are the reason for existence pseudogenes— inactive copies of functioning genes that lack expression, i.e. no functional protein is formed. In pseudogenes, mutations can accumulate. The process of tumor development is associated with the activation of pseudogenes.

There are two main reasons for the appearance of gene mutations: errors during the processes of replication, recombination and DNA repair (errors of the three Ps) and the action of mutagenic factors. An example of errors in the operation of enzyme systems during the above processes is non-canonical base pairing. It is observed when minor bases, analogues of ordinary ones, are included in the DNA molecule. For example, instead of thymine, bromuracil may be included, which combines quite easily with guanine. Due to this, the AT pair is replaced by GC.

Under the influence of mutagens, the transformation of one base into another can occur. For example, nitrous acid converts cytosine to uracil by deamination. In the next replication cycle, it pairs with adenine and the original GC pair is replaced by AT.

Chromosomal mutations

More serious changes in genetic material occur when chromosomal mutations. They are called chromosomal aberrations, or chromosomal rearrangements. Rearrangements can affect one chromosome (intrachromosomal) or several (interchromosomal).

Intrachromosomal rearrangements can be of three types: loss (lack) of a chromosome section; doubling of a chromosome section (duplication); rotation of a chromosome section by 180° (inversion). Interchromosomal rearrangements include translocations- movement of a section of one chromosome to another, non-homologous chromosome.

The loss of an internal part of a chromosome that does not affect telomeres is called deletions, and the loss of the end section is defiance. The detached section of the chromosome, if it lacks a centromere, is lost. Both types of deficiencies can be identified by the pattern of conjugation of homologous chromosomes in meiosis. In the case of a terminal deletion, one homologue is shorter than the other. In intrinsic deficiency, the normal homolog forms a loop against the lost homologue region.

Deficiencies lead to the loss of part of the genetic information, so they are harmful to the body. The degree of harm depends on the size of the lost area and its gene composition. Homozygotes for deficiencies are rarely viable. In lower organisms the effect of shortages is less noticeable than in higher ones. Bacteriophages can lose a significant part of their genome, replacing the lost section with foreign DNA, and at the same time retain functional activity. In the higher classes, even heterozygosity for deficiencies has its limits. Thus, in Drosophila, the loss of a region comprising more than 50 discs by one of the homologues has a lethal effect, despite the fact that the second homologue is normal.

In humans, a number of hereditary diseases are associated with deficiencies: severe form of leukemia (21st chromosome), cry-the-cat syndrome in newborns (5th chromosome), etc.

Deficiencies can be used for genetic mapping by establishing a link between the loss of a specific chromosomal region and the morphological characteristics of the individual.

Duplication called the doubling of any part of a chromosome of a normal chromosome set. As a rule, duplications lead to an increase in a trait that is controlled by a gene localized in this region. For example, doubling the gene in Drosophila Bar, causing a reduction in the number of eye facets, leads to a further decrease in their number.

Duplications are easily detected cytologically by disruption of the structural pattern of giant chromosomes, and genetically they can be identified by the absence of a recessive phenotype during crossing.

Inversion- rotating a section by 180° - changes the order of genes in the chromosome. This is a very common type of chromosomal mutation. Especially many of them were found in the genomes of Drosophila, Chironomus, and Tradescantia. There are two types of inversions: paracentric and pericentric. The former affect only one arm of the chromosome, without touching the centromeric region and without changing the shape of the chromosomes. Pericentric inversions involve the centromere region, which includes parts of both chromosome arms, and therefore can significantly change the shape of the chromosome (if the breaks occur at different distances from the centromere).

In prophase of meiosis, heterozygous inversion can be detected by a characteristic loop, with the help of which the complementarity of the normal and inverted regions of two homologues is restored. If a single crossover occurs in the inversion area, it leads to the formation of abnormal chromosomes: dicentric(with two centromeres) and acentric(without centromere). If the inverted area has a significant extent, then double crossing over can occur, as a result of which viable products are formed. In the presence of double inversions in one part of the chromosome, crossing over is generally suppressed, and therefore they are called “crossover suppressors” and are designated by the letter C. This feature of inversions is used in genetic analysis, for example, when taking into account the frequency of mutations (methods of quantitative accounting of mutations by G. Möller).

Interchromosomal rearrangements - translocations, if they have the nature of mutual exchange of sections between non-homologous chromosomes, are called reciprocal. If the break affects one chromosome and the torn section is attached to another chromosome, then this is - non-reciprocal translocation. The resulting chromosomes will function normally during cell division if each of them has one centromere. Heterozygosity for translocations greatly changes the process of conjugation in meiosis, because homologous attraction is experienced not by two chromosomes, but by four. Instead of bivalents, quadrivalents are formed, which can have different configurations in the form of crosses, rings, etc. Their incorrect divergence often leads to the formation of non-viable gametes.

With homozygous translocations, chromosomes behave as normal, and new linkage groups are formed. If they are preserved by selection, then new chromosomal races arise. Thus, translocations can be an effective factor in speciation, as is the case in some species of animals (scorpions, cockroaches) and plants (datura, peony, evening primrose). In the species Paeonia californica, all chromosomes are involved in the translocation process, and in meiosis a single conjugation complex is formed: 5 pairs of chromosomes form a ring (end-to-end conjugation).

The term "mutation" goes back to the Latin word "mutatio", which literally means change or change. Mutational variability denotes stable and obvious changes in the genetic material, which is shown in This is the first link in the chain of formation of hereditary diseases and pathogenesis. This phenomenon began to be actively studied only in the second half of the 20th century, and now one can increasingly hear that mutational variability should be studied, since knowledge and understanding of this mechanism is becoming key to overcoming the problems of mankind.

There are several types of mutations in cells. Their classification depends on the type of cells themselves. Generative mutations occur in germ cells; gametic cells also exist. Any changes are inherited and are often found in the cells of descendants; a number of abnormalities are passed on from generation to generation, which ultimately become the cause of diseases.

They belong to non-reproductive cells. Their peculiarity is that they appear only in the individual in whom they appeared. Those. changes are not inherited by other cells, but only when dividing in one organism. Somatic mutational variability is more noticeable when it begins in the early stages. If a mutation occurs in the first stages of zygote cleavage, then more cell lines with genotypes different from each other will arise. Accordingly, more cells will carry the mutation; such organisms are called mosaic.

Levels of hereditary structures

Mutational variability manifests itself in hereditary structures that differ in different levels of organization. Mutations can occur at the gene, chromosomal and genomic levels. Depending on this, the types of mutational variability also change.

Gene changes affect the structure of DNA, causing it to change at the molecular level. Such changes in some cases have no effect on the viability of the protein, i.e. the functions do not change at all. But in other cases, defective formations may occur, which already stops the ability of the protein to perform its function.

Mutations at the chromosomal level already pose a more serious threat, because they affect the formation of chromosomal diseases. The result of such variability is changes in the structure of chromosomes, and several genes are already involved here. Because of this, the usual diploid set may change, which in turn can generally affect the DNA.

Genomic mutations, just like chromosomal ones, can cause the formation of Examples of mutational variability at this level are aneuploidy and polyploidy. This is an increase or decrease in the number of chromosomes, which are most often lethal for humans.

Genomic mutations include trisomy, which means the presence of three homologous chromosomes in the karyotype (increase in number). This deviation leads to the formation of Edwards syndrome and Down syndrome. Monosomy means the presence of only one of two homologous chromosomes (reduced number), which practically eliminates the normal development of the embryo.

The cause of such phenomena is disturbances at different stages of development of germ cells. This occurs as a result of anaphase lag - homologous chromosomes move to the poles, and one of them may lag behind. There is also the concept of “non-disjunction”, when the chromosomes failed to separate at the stage of mitosis or meiosis. The result of this is the manifestation of violations of varying degrees of severity. Studying this phenomenon will help unravel the mechanisms and will probably make it possible to predict and influence these processes.