Mutation factors. What is a mutagenic factor and why is it dangerous? Factors that can cause mutation are called

Factors causing mutations

at the gene level

Under natural conditions, a mutation appears under the influence of external and internal environmental factors and is designated by the term “natural (or spontaneous) mutations.”

The cause of gene, or so-called point, mutations is the replacement of one nitrogenous base in the D.N.K. molecule. to another, loss, insertion, or rearrangement of nitrogenous bases in the D.N.K. molecule. It follows that when a gene mutates, a person can develop pathological conditions, the pathogenesis of which is different.

The factors causing mutations at the gene level were influenced by the environment (gout, some forms of diabetes). Such diseases more often occur with constant exposure to unfavorable or harmful environmental factors (diet disorders, etc.). A gene mutation can lead to a disruption in the synthesis of proteins that perform plastic functions. The probable cause of such diseases is Ehlers-Danlos syndrome.

Diseases based on insufficient mechanisms for restoring the altered D.N.K. molecule are being studied.

A number of mutations of genes that control the synthesis of blood clotting factors are known.

Gene mutations can cause disruption of the transport of various compounds across cell membranes. They are associated with dysfunction of membrane mechanisms and with defects in some systems.

If a mutation at the gene level occurs under the influence of various physical, chemical, biological factors, then this is called mutagenesis.

The basis of the mutation is primary damage in the D.N.K. molecule.

In practice, methods must be developed to establish the degree of risk, either in individual families or by screening all parents. This will change the purpose of medical genetics from a genetics counseling service on a retrospective basis to a genetic warning service on a prospective basis. A new attitude may arise towards the responsibility of parents for the reproduction of offspring, which, together with...

Protein product; mutations in the polyadenylation site reduce the level of transcription (typical for African Americans suffering from thalassemia; for details on hemoglobinopathies, see Part P, Medical Genetics). Thus, mutations in the regulatory 5" and 3" untranslated regions of genes cause quantitative changes in the corresponding products and manifest themselves phenotypically (clinically) depending...

Existence is natural selection. Darwin used this term to describe “the preservation of favorable individual differences and changes and the elimination of harmful ones.” The struggle for existence and natural selection based on hereditary variability are, according to Darwin, the main driving forces (factors) in the evolution of the organic world. Individual hereditary deviations, the struggle for existence and...

No matter how the phenotype of an organism changes in response to environmental influences, its changes cannot lead to changes in the genes that this organism will pass on to the next generation. 1.4 The role of chromosomal and genomic mutations in evolution All of the above characteristics are true for all types of mutations - gene, chromosomal and genomic. However, such genomic and chromosomal mutations as polyploidy (...

Factors causing mutations. Factors that cause (induce) mutations can be a wide variety of environmental influences: temperature, ultraviolet radiation, radiation (both natural and artificial), the actions of various chemical compounds - mutagens. Mutagens are agents of the external environment that cause certain changes in the genotype - mutation, and the process of formation of mutations is called mutagenesis.

Radioactive mutagenesis began to be studied in the 20s of our century. In 1925, Soviet scientists G.S. Filippov and G.A. Nadson, for the first time in the history of genetics, used X-rays to obtain mutations in yeast. A year later, the American researcher G. Meller (later twice a Nobel Prize winner), who worked for a long time in Moscow at the institute headed by N.K. Koltsov, used the same mutagen on Drosophila.

Chemical mutagenesis was first purposefully studied by N.K. Koltsov’s collaborator V.V. Sakharov in 1931 on Drosophila when its eggs were exposed to iodine, and later by M.E. Lobashov.

Chemical mutagens include a wide variety of substances (alkylating compounds, hydrogen peroxide, aldehydes and ketones, nitric acid and its analogues, various antimetabolites, salts of heavy metals, dyes with basic properties, aromatic substances), insecticides (from the Latin insecta - insects , cida - killer), herbicides (then lat. herba - grass), drugs, alcohol, nicotine, some medicinal substances and many others.

Genetically active factors can be divided into 3 categories: physical, chemical and biological.

Physical factors. These include various types of ionizing radiation and ultraviolet radiation. A study of the effect of radiation on the mutation process showed that in this case there is no threshold dose, and even the smallest doses increase the likelihood of mutations occurring in the population. An increase in the frequency of mutations is dangerous not so much in an individual sense, but from the point of view of increasing the genetic load of the population. For example, irradiation of one of the spouses with a dose within the range of doubling the frequency of mutations (1.0 - 1.5 Gy) slightly increases the risk of having a sick child (from a level of 4 - 5% to a level of 5 - 6%). If the population of an entire region receives the same dose, the number of hereditary diseases in the population will double in a generation.

Chemical factors. The chemicalization of agriculture and other areas of human activity, the development of the chemical industry led to the synthesis of a huge flow of substances (totaling from 3.5 to 4.3 million), including those that had never existed in the biosphere for millions of years of previous evolution. This means, first of all, the indegradability and thus long-term preservation of foreign substances entering the environment. What was initially taken as an achievement in the fight against pests later turned into a complex problem. The widespread use in the 40-60s of the insecticide DDT, which belongs to the class of chlorinated hydrocarbons, led to its spread throughout the globe, right up to the ice of Antarctica.

Most pesticides are highly resistant to chemical and biological degradation and have a high level of toxicity.

Biological factors. Along with physical and chemical mutagens, some factors of biological nature also have genetic activity. The mechanisms of the mutagenic effect of these factors have been studied in the least detail. At the end of the 30s, S. and M. Gershenzon began research on mutagenesis in Drosophila under the influence of exogenous DNA and viruses. Since then, the mutagenic effect of many viral infections in humans has been established. Chromosome aberrations in somatic cells are caused by smallpox, measles, chickenpox, mumps, influenza, hepatitis, etc. viruses.

3. Gene and chromosomal mutations, their characteristics.

Gene (point) mutations- these are changes in the number and/or sequence of nucleotides in the DNA structure (insertions, deletions, movements, substitutions of nucleotides) within individual genes, leading to a change in the quantity or quality of the corresponding protein products. Base substitutions lead to the appearance of three types of mutant codons: with a changed meaning (missense mutations), with an unchanged meaning (neutral mutations) and meaningless or stop codons (nonsense mutations).

There are three groups of such changes. Mutations of the first group consist of replacing some bases with others (about 20% of spontaneously occurring gene changes). The second group of mutations is caused by a shift in the reading frame that occurs when the number of nucleotide pairs in the gene changes. The third group is mutations associated with a change in the order of nucleotide sequences within a gene.

Mutations by type of replacement of nitrogenous bases occur due to the following reasons. Firstly, a change in the structure of a base already included in the DNA helix can occur accidentally or under the influence of chemical agents. If such an altered form of the base remains undetected by repair enzymes, then during the next replication cycle it can attach another nucleotide to itself.

Another reason for base substitution may be the erroneous inclusion in the synthesized DNA chain of a nucleotide carrying a chemically altered form of the base or its analogue. Thus, a change in DNA structure by base substitution occurs before or during replication, initially in one polynucleotide chain. If such changes are not corrected during repair, then during subsequent replication they become the property of both DNA strands. The consequence of replacing one pair of complementary nucleotides with another is the formation of a new triplet in the DNA nucleotide sequence, different from the previous one. In this case, the new triplet can encode the same amino acid (a “synonym” triplet), another amino acid, or not encode any amino acid (a nonsense triplet). In the first case, no changes occur, in the second, the structure and properties of the corresponding protein change. Depending on the nature and location of the replacement that occurs, the specific properties of the protein change to varying degrees, in some cases significantly. It is known that replacing nucleotides in one triplet leads to the formation of synonymous triplets in 25% of cases, meaningless triplets in 2-3%, and true gene mutations in 75-70% of cases.

Chromosomal mutations(or aberrations) – changes in the structure of chromosomes. At the chromosomal level of organization, the hereditary material has all the characteristics of the substrate of heredity and variability, including the ability to acquire changes that can be transmitted to a new generation. Under the influence of various influences, the physicochemical and morphological structure of chromosomes can change. Changes in the structure of chromosomes, as a rule, are based on an initial violation of its integrity - breaks, which are accompanied by various rearrangements, called chromosomal mutations or aberrations. Chromosome breaks occur naturally during crossing over, when they are accompanied by the exchange of corresponding sections between homologous chromosomes. Crossing-over disruption, in which chromosomes exchange unequal genetic material, leads to the appearance of new linkage groups, where individual sections fall out - deletion - or double - duplication. With such rearrangements, the number of genes in the linkage group changes. Chromosome breaks can also occur under the influence of various external factors, most often physical (for example, ionizing radiation), certain chemical compounds, and viruses. Violation of the integrity of chromosomes can be accompanied by a rotation of its section located between the breaks by 180° - inversion. A fragment of a chromosome separated from it during a break can attach to another chromosome - translocation. Often, two damaged non-homologous chromosomes mutually exchange detached sections - reciprocal translocation. It is possible to attach a fragment to its own chromosome, but in another place - transposition. A special category of chromosomal mutations are aberrations associated with the fusion or separation of chromosomes, when two non-homologous structures combine into one - Robertsonian translocation, or one chromosome forms two independent chromosomes. With such mutations, not only the morphology of chromosomes changes, but also their number in the karyotype changes. The latter can be considered a genomic mutation. The cause of genomic mutations can also be a disruption of the processes occurring in meiosis. Violation of the divergence of bivalents in anaphase leads to the appearance of gametes with different numbers of chromosomes. Fertilization of such gametes by normal germ cells leads to a change in the total number of chromosomes in the karyotype due to a decrease (monosomy) or increase (trisomy) in the number of individual chromosomes. Such violations of the genome structure are called aneuploidy. If the mechanism of distribution of homologous chromosomes is damaged, the cell remains undivided, and then diploid gametes are formed. Fertilization of such gametes leads to the formation of triploid zygotes, that is, an increase in the number of sets of chromosomes occurs - polyploidy. Any mutational changes in the hereditary material of gametes - generative mutations - become the property of the next generation if such gametes are involved in fertilization.

There are many inherited metabolic diseases. Examples include disorders of porphyrin metabolism (Gunther's disease, erythropoietic protoporphyria, coproporphyria, etc.). These are diseases that manifest themselves after exposure to UV rays by damage to the skin and deeper tissues, an increased content of proporphins and coproporphyrins in erythrocytes. They appear among brothers and sisters of the same generation.

Under natural conditions, a mutation appears under the influence of external and internal environmental factors and is designated by the term “natural (or spontaneous) mutations.”

The cause of gene, or so-called point, mutations is the replacement of one nitrogenous base in the DNA molecule. to another, the loss, insertion, or rearrangement of nitrogenous bases in a DNA molecule. It follows that when a gene mutates, a person can develop pathological conditions, the pathogenesis of which is different.

A gene mutation can lead to the development of immunodeficiency diseases (thymic aplasia combined with agammaglobulinemia). The reason for the abnormal structure of hemoglobin is the replacement of a glutamic acid residue in the molecule with a valine residue. A number of mutations of genes that control the synthesis of blood clotting factors are known. Gene mutations can cause disruption of the transport of various compounds across cell membranes. They are associated with dysfunction of membrane mechanisms and with defects in some systems.

If a mutation at the gene level occurs under the influence of various physical, chemical, biological factors, then this is called mutagenesis. The basis of mutation is primary damage in the DNA molecule.

Mutagens

Mutagens (from the Greek γεννάω - I give birth) are chemical and physical factors that cause hereditary changes - mutations. Artificial mutations were first obtained in 1925 by G. A. Nadsen and G. S. Filippov in yeast by the action of radium radiation; in 1927, G. Möller obtained mutations in Drosophila by exposure to X-rays. The ability of chemical substances to cause mutations (by the effect of iodine on Drosophila) was discovered by I. A. Rapoport. In flies that developed from these larvae, the frequency of mutations was several times higher than in control insects.

Classification

Mutagens can be various factors that cause changes in the structure of genes, the structure and number of chromosomes. Based on their origin, mutagens are classified into endogenous, formed during the life of the body, and exogenous - all other factors, including environmental conditions.

Based on the nature of their occurrence, mutagens are classified into physical, chemical and biological:

1. Physical mutagens

Ionizing radiation;
radioactive decay;
ultraviolet radiation;
simulated radio emission and electromagnetic fields;
excessively high or low temperature.

2. Chemical mutagens

Oxidizing agents and reducing agents (nitrates, nitrites, reactive oxygen species);
alkylating agents (eg iodoacetamide);
pesticides (eg herbicides, fungicides);
some food additives (for example, aromatic hydrocarbons, cyclamates);
petroleum products;
organic solvents;
medications (for example, cytostatics, mercury preparations, immunosuppressants).
A number of viruses can also be classified as chemical mutagens (the mutagenic factor of viruses is their nucleic acids - DNA or RNA)

3. Biological mutagens

Specific DNA sequences are transposons;
some viruses (measles, rubella, influenza virus);
metabolic products (lipid oxidation products);
antigens of some microorganisms.

Mutation factors. What is a mutagenic factor and why is it dangerous? Factors that can cause mutation are called

More on the topic Factors causing mutations of the hereditary apparatus:

3. Gene and chromosomal mutations, their characteristics.