Causes of mutations. Features of mutational variability

Mutation(from Latin word"mutatio" - change) is permanent change genotype, which occurred under the influence of internal or external factors. There are chromosomal, gene and genomic mutations.

What are the causes of mutations?

• Unfavourable conditions environment, conditions created experimentally. Such mutations are called induced.
• Some processes occurring in a living cell of an organism. For example: DNA repair disorder, DNA replication, genetic recombination.

Mutagens are factors that cause mutations. Are divided into:

• Physical - radioactive decay, and ultraviolet, too heat or too low.
• Chemical - reducing and oxidizing agents, alkaloids, alkylating agents, urea nitro derivatives, pesticides, organic solvents, some medications.
• Biological - some viruses, metabolic products (metabolism), antigens of various microorganisms.

Basic properties of mutations

• Passed on by inheritance.
• Caused by a variety of internal and external factors.
• They appear spasmodically and suddenly, sometimes repeatedly.
• Any gene can mutate.

What are they?

• Genomic mutations are changes that are characterized by the loss or addition of one chromosome (or several) or the complete haploid set. There are two types of such mutations - polyploidy and heteroploidy.

Polyploidy is a change in the number of chromosomes that is a multiple of haploid set. Extremely rare in animals. There are two types of polyploidy possible in humans: triploidy and tetraploidy. Children born with such mutations usually live no more than a month, and more often die in the embryonic development stage.

Heteroploidy(or aneuploidy) is a change in the number of chromosomes that is not a multiple of the halogen set. As a result of this mutation, individuals are born with an abnormal number of chromosomes - polysomics and monosomics. About 20-30 percent of monosomics die in the first days intrauterine development. Among the births there are individuals with Shereshevsky-Turner syndrome. Genomic mutations in the plant and animal world are also diverse.

• - these are changes that occur when the structure of chromosomes is rearranged. In this case, there is a transfer, loss or doubling of part of the genetic material of several chromosomes or one, as well as a change in the orientation of chromosomal segments in individual chromosomes. In rare cases, a union of chromosomes is possible.

• Gene mutations. As a result of such mutations, insertions, deletions or substitutions of several or one nucleotides occur, as well as inversion or duplication different parts gene. The effects of gene type mutations are varied. Most of of them are recessive, that is, they do not manifest themselves in any way.

Mutations are also divided into somatic and generative

• - in any cells of the body, except gametes. For example, when a plant cell mutates, from which a bud should subsequently develop, and then a shoot, all its cells will be mutant. So, on a red currant bush a branch with black or white berries may appear.

• Generative mutations are changes in the primary germ cells or in the gametes that were formed from them. Their properties are passed on to the next generation.

According to the nature of the effect on mutations, there are:

• Lethal - the owners of such changes die either in the stage or after sufficient a short time after birth. These are almost all genomic mutations.
• Semi-lethal (for example, hemophilia) - characterized by sharp deterioration operation of any systems in the body. In most cases, semi-lethal mutations also lead to death soon after.
• Beneficial Mutations- this is the basis of evolution, they lead to the appearance of characteristics, needed by the body. Once established, these characteristics can cause the formation of a new subspecies or species.

When changes occur spontaneously in DNA, causing in living organisms various pathologies development and growth, they talk about mutations. To understand their essence, it is necessary to learn more about the reasons leading to them.

Geneticists claim that mutations are characteristic of all organisms on the planet without exception (living ones) and that they have existed forever, and one organism can have several hundred of them. However, they differ in the degree of severity and nature of manifestation, which are determined by the factors that provoke them, as well as the affected gene chain.

They can be natural and artificial, i.e. caused in laboratory conditions.

Most common factors, leading to such changes from the point of view of geneticists, are as follows:

ionizing radiation and X-rays. Influencing the body radioactive radiation accompanied by a change in the electron charge in the atoms. This causes a disruption in the normal course of physico-chemical and chemical-biological processes;

very high temperatures often cause changes when the sensitivity threshold of a particular individual is exceeded;

when cells divide, delays may occur, as well as their proliferation too quickly, which also becomes an impetus for negative changes;

“defects” that occur in DNA, in which it is not possible to return the atom to its original state even after restoration.

Varieties

On this moment There are more than thirty types of deviations in the gene pool of a living organism and genotype that cause mutations. Some are quite safe and do not manifest themselves in any way externally, i.e. do not lead to internal and external deformities, so the living organism does not feel discomfort. Others, on the contrary, are accompanied by severe discomfort.

To understand what mutations are, you should familiarize yourself with the mutagenic classification, grouped according to the causes of defects:

genetic and somatic, differing in the typology of cells that have undergone changes. Somatic is characteristic of mammalian cells. They can be passed on solely by inheritance (for example, different eye colors). Its formation occurs in the mother's womb. Genetic mutation characteristic of plants and invertebrates. Call her negative factors environment. An example of a manifestation is mushrooms appearing on trees, etc.;

nuclear refer to mutations based on the location of the cells that have undergone changes. Such options cannot be treated, since the DNA itself is directly affected. The second type of mutation is cytoplasmic (or atavism). It affects any fluids that interact with the cell nucleus and the cells themselves. Such mutations are treatable;

explicit (natural) and induced (artificial). The appearance of the first suddenly and without visible reasons. The latter are associated with the failure of physical or chemical processes;

gene and genomic, differing in their severity. In the first variant, the changes concern disorders that change the sequence of nucleotide structure in newly formed DNA chains (phenylketonuria can be considered as an example).

In the second case, there is a change in the quantitative chromosome set, and the example is Down's disease, Konovalov-Wilson's disease, etc.

Meaning

The harm of mutations to the body is undeniable, since it not only affects its normal development, but often leads to fatal outcome. Mutations cannot be beneficial. This also applies to cases of superpowers. They are always prerequisites for natural selection, leading to the emergence of new species of organisms (living) or to complete extinction.

It is now clear that processes that affect the structure of DNA, leading to minor or fatal disorders, affect normal development and vital activity of the body.

Mutations are spontaneous changes in the DNA structure of living organisms, leading to various abnormalities in growth and development. So, let's look at what a mutation is, the reasons for its occurrence and its existence. It is also worth paying attention to the impact of genotype changes on nature.

Scientists say that mutations have always existed and are present in the bodies of absolutely all living creatures on the planet; moreover, up to several hundred of them can be observed in one organism. Their manifestation and degree of expression depend on what causes they were provoked and which genetic chain was affected.

Causes of mutations

The causes of mutations can be very diverse, and they can arise not only naturally, but also artificially, in laboratory conditions. Genetic scientists identify the following factors for the occurrence of changes:

2) gene mutations - changes in the sequence of nucleotides during the formation of new DNA chains (phenylketonuria).

The meaning of mutations

In most cases, they harm the entire body because they interfere with its normal growth and development, and sometimes lead to death. Beneficial mutations never occur, even if they provide superpowers. They become a prerequisite for active action and influence the selection of living organisms, leading to the emergence of new species or degeneration. Thus, answering the question: “What is a mutation?” - it is worth noting that these are the slightest changes in the structure of DNA that disrupt the development and vital functions of the entire organism.

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 they work various systems reparations that 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 conditions external environment 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 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 long time persist in a population in a heterozygous state and manifest as a result of combinative variability. If the resulting mutation has beneficial influence 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 suppress or disrupt the synthesis of certain chemical substances, usually as a result of the absence 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 may occur on different stages development of germ cells. The sooner they arise, the large quantity the gametes will carry them, and therefore increase the chance of their transmission to offspring. 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 be 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.

To appear gene mutations There are two main reasons: 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 nature of the conjugation homologous chromosomes in meiosis. In the case of a terminal deletion, one homologue is shorter than the other. At internal shortage the normal homolog forms a loop against the lost homolog 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. U lower organisms the effect of shortages is less noticeable than that of the higher ones. Bacteriophages can lose a significant part of their genome, replacing the lost section of 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.

A person has a number of deficiencies associated with hereditary diseases: 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 region 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 when 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 effective factor speciation, as occurs 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).

Causes of mutations

Mutations are divided into spontaneous And induced. Spontaneous mutations occur spontaneously throughout the life of an organism under normal environmental conditions with a frequency of about 10 to the −9 power - 10 to −12 per nucleotide per cell generation. Induced mutations are heritable changes in the genome that arise as a result of certain mutagenic effects in artificial (experimental) conditions or under adverse environmental influences.

Mutations appear constantly during processes occurring in a living cell. The main processes leading to the occurrence of mutations are DNA replication, DNA repair disorders and genetic recombination.

Relationship between mutations and DNA replication

Many spontaneous chemical changes in nucleotides lead to mutations that occur during replication. For example, due to the deamination of cytosine opposite it, uracil can be included in the DNA chain (a U-G pair is formed instead of the canonical pairs C-G). During DNA replication, adenine is included in the new chain opposite uracil, forming couple U-A, and during the next replication it is replaced by the T-A pair, that is, a transition occurs.

Relationship between mutations and DNA recombination

Of the processes associated with recombination, unequal crossing over most often leads to mutations. It usually occurs in cases where there are several duplicated copies of the original gene on the chromosome that have retained a similar nucleotide sequence. As a result of unequal crossing over, duplication occurs in one of the recombinant chromosomes, and deletion occurs in the other.

Relationship between mutations and DNA repair

Spontaneous DNA damage is quite common and occurs in every cell. To eliminate the consequences of such damage, there are special repair mechanisms (for example, an erroneous section of DNA is cut out and the original one is restored at this place). Mutations occur only when the repair mechanism for some reason does not work or cannot cope with the elimination of damage. Mutations that occur in the genes of proteins responsible for repair can lead to a multiple increase (mutator effect) or decrease (antimutator effect) in the frequency of mutation of other genes. Thus, mutations in the genes of many enzymes of the excision repair system lead to sharp increase frequency of somatic mutations in humans, and this, in turn, leads to the development of xeroderma pigmentosum and malignant tumors covers.

Mutagens

There are factors that can significantly increase the frequency of mutations - mutagenic factors. These include:

• chemical mutagens - substances that cause mutations,
• physical mutagens - ionizing radiation, including natural background radiation, ultraviolet radiation, high temperature, etc.,
• biological mutagens - for example, retroviruses, retrotransposons.

Mutation classifications

There are several classifications of mutations according to various criteria. Möller proposed dividing mutations according to the nature of the change in the functioning of the gene into hypomorphic(altered alleles act in the same direction as wild-type alleles; only less is synthesized protein product), amorphous(a mutation looks like a complete loss of gene function, e.g. white in Drosophila), antimorphic(the mutant trait changes, for example, the color of the corn grain changes from purple to brown) and neomorphic.

Modern educational literature also uses a more formal classification based on the nature of changes in the structure of individual genes, chromosomes and the genome as a whole. Within this classification there are the following types mutations:

• genetic
• chromosomal
• genomic.

Consequences of mutations for cells and organisms

Mutations that impair cell activity in a multicellular organism often lead to cell destruction (in particular, programmed cell death - apoptosis). If intra- and extracellular defense mechanisms did not recognize the mutation and the cell went through division, then the mutant gene will be passed on to all the descendants of the cell and, most often, leads to the fact that all these cells begin to function differently.

The role of mutations in evolution

With a significant change in living conditions, those mutations that were previously harmful may turn out to be useful. Thus, mutations are the material for natural selection. Thus, melanistic mutants (dark-colored individuals) in populations of the birch moth (Biston betularia) in England were first discovered by scientists among typical light-colored individuals in the middle of the 19th century. Dark coloring occurs as a result of a mutation in one gene. Butterflies spend the day on the trunks and branches of trees, usually covered with lichens, against which the light coloring acts as a camouflage. As a result of the industrial revolution, accompanied by air pollution, the lichens died and the light trunks of birches became covered with soot. As a result, by the middle of the 20th century (over 50-100 generations), in industrial areas the dark morph almost completely replaced the light one. It has been shown that main reason the predominant survival of the black form was predation by birds, which selectively ate light-colored butterflies in polluted areas.

If a mutation affects “silent” sections of DNA, or leads to the replacement of one element of the genetic code with a synonymous one, then it usually does not manifest itself in the phenotype (the manifestation of such a synonymous substitution may be associated with different frequencies of codon use). However, such mutations can be detected using gene analysis methods. Since mutations most often occur as a result natural causes, then, assuming that the basic properties of the external environment have not changed, it turns out that the mutation rate should be approximately constant. This fact can be used to study phylogeny - study the origin and relationships of various taxa, including humans. Thus, mutations in silent genes serve as a kind of “molecular clock” for researchers. The “molecular clock” theory also proceeds from the fact that most mutations are neutral, and the rate of their accumulation in a given gene does not depend or weakly depends on the action of natural selection and therefore remains constant for a long time. This rate will, however, differ for different genes.

The study of mutations in mitochondrial DNA (inherited on the maternal line) and in Y chromosomes (inherited on the paternal line) is widely used in evolutionary biology to study the origin of races and nationalities and reconstruct the biological development of mankind.

The problem of random mutations

In the 40s, a popular point of view among microbiologists was that mutations are caused by exposure to an environmental factor (for example, an antibiotic), to which they allow adaptation. To test this hypothesis, the fluctuation test and replica method were developed.
The Luria-Delbrück fluctuation test consists of dispersing small portions of the original bacterial culture into test tubes containing liquid medium, and after several cycles of divisions, an antibiotic is added to the test tubes. Then (without subsequent divisions) the surviving antibiotic-resistant bacteria are seeded onto Petri dishes with solid medium. The test showed. that the number of resistant colonies from different tubes is very variable - in most cases it is small (or zero), and in some cases it is very high. This means that the mutations that caused resistance to the antibiotic arose at random points in time both before and after exposure to it.
The replica method (in microbiology) is that from the original Petri dish, where colonies of bacteria grow on a solid medium, an imprint is made onto fleecy fabric, and then the bacteria are transferred from the tissue to several other dishes, where the pattern of their location turns out to be the same as on the original cup. After exposure to the antibiotic, colonies located at the same points survive on all plates. By plating such colonies on new plates, it can be shown that all bacteria within the colony are resistant.
Thus, both methods proved that “adaptive” mutations arise regardless of the influence of the factor to which they allow adaptation, and in this sense, mutations are random. However, there is no doubt that the possibility of certain mutations depends on the genotype and is canalized by the previous course of evolution (see the Law of homological series in hereditary variability). In addition, the frequency of mutations of different genes and different regions within one gene naturally varies. It is also known that higher organisms use “targeted” (that is, occurring in certain sections of DNA) mutations in immunity mechanisms. With their help, a variety of lymphocyte clones is created, among which, as a result, there are always cells capable of giving an immune response to a new disease unknown to the body. Suitable lymphocytes are subject to positive selection, resulting in immunological memory.

see also

Links

Inge-Vechtomov S.V. Genetics with the basics of selection. M., graduate School, 1989.

Notes

Wikimedia Foundation. 2010.