Chromosomal, gene and genomic mutations and their properties. Types of mutations in humans

The hereditary information of a cell is recorded in the form of a DNA nucleotide sequence. There are mechanisms to protect DNA from external influences in order to avoid damage to genetic information, however, such violations occur regularly, they are called mutations.

Mutations- changes that have arisen in the genetic information of the cell, these changes can have a different scale and are divided into types.

Mutation types

Genomic mutations- changes concerning the number of whole chromosomes in the genome.

Chromosomal mutations- changes relating to regions within the same chromosome.

Gene mutations- changes occurring within a single gene.

As a result of genomic mutations, there is a change in the number of chromosomes within the genome. This is due to a malfunction of the division spindle, thus, homologous chromosomes do not diverge to different poles of the cell.

As a result, one cell acquires twice as many chromosomes as it should (Fig. 1):

Rice. 1. Genomic mutation

The haploid set of chromosomes remains the same, only the number of sets of homologous chromosomes (2n) changes.

In nature, such mutations are often fixed in the offspring; they occur most often in plants, as well as in fungi and algae (Fig. 2).

Rice. 2. Higher plants, mushrooms, algae

Such organisms are called polyploid, polyploid plants can contain from three to one hundred haploid sets. Unlike most mutations, polyploidy most often benefits the body, polyploid individuals are larger than normal ones. Many cultivars of plants are polyploid (Fig. 3).

Rice. 3. Polyploid crop plants

A person can artificially induce polyploidy by influencing plants with colchicine (Fig. 4).

Rice. 4. Colchicine

Colchicine destroys the spindle fibers and leads to the formation of polyploid genomes.

Sometimes during division, non-disjunction in meiosis may occur not for all, but only for some chromosomes, such mutations are called aneuploid. For example, the mutation trisomy 21 is typical for a person: in this case, the twenty-first pair of chromosomes does not diverge, as a result, the child receives not two twenty-first chromosomes, but three. This leads to the development of Down syndrome (Fig. 5), as a result of which the child is mentally and physically handicapped and sterile.

Rice. 5. Down syndrome

A variety of genomic mutations is also the division of one chromosome into two and the fusion of two chromosomes into one.

Chromosomal mutations are divided into types:

- deletion- loss of a chromosome segment (Fig. 6).

Rice. 6. Deletion

- duplication- duplication of some part of the chromosomes (Fig. 7).

Rice. 7. Duplication

- inversion- rotation of a chromosome region by 180 0, as a result of which the genes in this region are located in a reverse sequence compared to the norm (Fig. 8).

Rice. 8. Inversion

- translocation- moving any part of the chromosome to another place (Fig. 9).

Rice. 9. Translocation

With deletions and duplications, the total amount of genetic material changes, the degree of phenotypic manifestation of these mutations depends on the size of the altered areas, as well as on how important genes got into these areas.

During inversions and translocations, the amount of genetic material does not change, only its location changes. Such mutations are evolutionarily necessary, since mutants often can no longer interbreed with the original individuals.

Bibliography

1. Mamontov S.G., Zakharov V.B., Agafonova I.B., Sonin N.I. Biology, 11th grade. General biology. Profile level. - 5th edition, stereotypical. - Bustard, 2010.
2. Belyaev D.K. General biology. A basic level of. - 11th edition, stereotypical. - M.: Education, 2012.
3. Pasechnik V.V., Kamensky A.A., Kriksunov E.A. General biology, grades 10-11. - M.: Bustard, 2005.
4. Agafonova I.B., Zakharova E.T., Sivoglazov V.I. Biology 10-11 class. General biology. A basic level of. - 6th ed., add. - Bustard, 2010.

1. Internet portal "genetics.prep74.ru" ()
2. Internet portal "shporiforall.ru" ()
3. Internet portal "licey.net" ()

Homework

1. Where are genome mutations most common?
2. What are polyploid organisms?
3. What are the types of chromosomal mutations?

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. By the nature of the change in the genome, i.e. sets of genes contained in the haploid set of chromosomes distinguish between gene, chromosomal and genomic mutations. 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 impact on viability. Some mutations have no effect on the structure and function of the corresponding protein. Another (most) part of gene mutations leads to the synthesis of a defective protein that is unable to perform its proper function.

According to 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 re-duplication of a DNA segment from one nucleotide to entire genes;

Inversions (from the Latin inversio - turning over), i.e. a 180° turn of a DNA segment ranging in size from two nucleotides to a fragment that includes several genes;

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

It is gene mutations that cause the development of most hereditary forms of pathology. Diseases caused by such mutations are called gene or monogenic diseases, i.e. diseases, the development of which is determined by a mutation of a single 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 of the newly emerging mutations are harmful. However, their recessive nature allows them long time persist in individuals of the species in a heterozygous state without harm to the body and manifest itself in the future when switching to a homozygous state.

Currently, there are more than 4500 monogenic diseases. The most common of them are: cystic fibrosis, phenylketonuria, Duchenne-Becker myopathies and a number of other diseases. Clinically, they are manifested by signs of metabolic disorders (metabolism) in the body.

At the same time, a number of cases are known when a change in only one base in a particular gene has a noticeable effect on the phenotype. One example is a genetic anomaly such as sickle cell anemia. The recessive allele that causes this hereditary disease in the homozygous state is expressed in the replacement of only one amino acid residue in the (B-chain of the hemoglobin molecule (glutamic acid? ?> valine). This leads to the fact that red blood cells with such hemoglobin are deformed in the blood (from rounded become sickle-shaped) and are quickly destroyed.At the same time, acute anemia develops and there is a decrease in the amount of oxygen carried by the blood.Anemia causes physical weakness, disorders 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 in individual chromosomes, usually visible under a light microscope. A large number (from tens to several hundreds) of genes is involved in a chromosomal mutation, which leads to a change in the normal diploid set. Although chromosomal aberrations generally do not change the DNA sequence in specific genes, changing the copy number of genes in the genome leads to a 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 - the loss of one of the sections of the chromosome, internal or terminal. This can lead to a violation 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 as 5p-, leads to underdevelopment of the larynx, heart defects, mental retardation. This symptom complex is known as the "cat's cry" 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 breaks in the chromosome, the resulting fragment is inserted into its original place after a rotation of 180°. As a result, only the order of the genes is violated;

Duplications - doubling (or multiplication) of any part of the chromosome (for example, trisomy along the short arm of the 9th chromosome 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). It:

Reciprocal translocation - two chromosomes exchange their fragments;

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

? "centric" fusion (Robertsonian translocation) - the connection of two acrocentric chromosomes in the region of their centromeres with the loss of short arms.

With transverse chromatid breakage through the 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, as well as chromosomal, are the causes of chromosomal diseases.

Genomic mutations include aneuploidy 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 multiple of a haploid one (2n + 1, 2n-1, etc.).

Polyploidy - 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, for the 21st pair with Down's disease, for the 18th pair for Edwards syndrome, for the 13th pair for 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, the 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 lagging, when one of the homologous chromosomes may lag behind other non-homologous chromosomes during movement to the pole. The term nondisjunction means the absence of separation of chromosomes or chromatids in meiosis or mitosis.

Chromosome nondisjunction is most commonly observed during meiosis. Chromosomes, which normally should divide during meiosis, remain joined together and move to one pole of the cell in anaphase, thus two gametes arise, 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 extra chromosome trisomy occurs (i.e., there are three homologous chromosomes in the cell), when fertilized by a gamete without one chromosome, a zygote with monosomy occurs. If a monosomic zygote is formed on any autosomal chromosome, then the development of the organism stops at the very early stages development.

According to the type of inheritance dominant and recessive mutations. Some researchers distinguish semi-dominant, co-dominant mutations. Dominant mutations are characterized by a direct effect on the body, semi-dominant mutations are that the heterozygous form in phenotype is intermediate between the AA and aa forms, and codominant mutations are characterized by the fact that A 1 A 2 heterozygotes 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 a heterozygous form of Aa, intermediate in phenotype between AA and aa organisms. This takes place in the case of biochemical traits, when the contribution to the trait of both alleles is the same.

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

In the case of recessive mutations, their effects are hidden in the 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 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 an organism of the original (wild) type goes directly to the mutant type organism.

Back mutations are reversions to the original (wild) types from mutant ones. These reversions are of two types. Some of the reversions are due to repeated mutations of a similar site or locus with the restoration of the original phenotype and are called true backmutations. 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 is preserved, but it somehow restores its function, as a result of which the phenotype is restored. Such a restoration (full or partial) of the phenotype despite the preservation of the original genetic damage (mutation) was called suppression, and such back mutations were called suppressor (extragene). As a rule, suppressions occur as a result of mutations in genes encoding the synthesis of tRNA and ribosomes.

AT general view 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. At the same time, this amino acid does not correspond to the original one (before the appearance of the first mutation), i.e. no true reversibility observed;

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

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

Mutations, in addition to qualitative properties, also characterize the way they occur. Spontaneous(random) - mutations that occur under normal living conditions. They are the result natural processes occurring in cells arise under the conditions of the Earth's natural radioactive background in the form of cosmic radiation, radioactive elements on the Earth's surface, 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 a dominant trait appears in children, although its 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 nature. There are physical, chemical and biological mutagenic factors. Most of these factors either directly react with nitrogenous bases in DNA molecules or are incorporated into nucleotide sequences. The frequency of induced mutations is determined by comparing cells or populations of organisms treated with and untreated with the mutagen. If the mutation rate in a population is increased by a factor of 100 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 directed action of various mutagens on specific genes is of practical importance for the selection of plants, animals, and microorganisms.

According to 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 germ and in 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 to inherit this mutation by several individuals (individuals) in the offspring. If the mutation occurred in the 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. four.

Somatic mutations occur in somatic cells of organisms. In animals and humans, mutational changes will persist only in these cells. But in plants, because of their ability to reproduce vegetatively, the mutation can go beyond somatic tissues. For example, the famous winter variety of Delicious apples originates from a mutation in the 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 were allocated:

amorphous mutations. This is a condition in which the trait controlled by the abnormal allele does not occur because the abnormal allele is not active compared to the normal allele. These 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. These mutations include the 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 genome instability disease genes. 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, pigment xeroderma, Bloom's syndrome, progeroid syndromes, many forms of cancer, etc. At the same time, the frequency of cancer in heterozygous carriers of the genes for these diseases is 3-5 times higher than in the norm, and in the patients themselves ( homozygotes for these genes) the incidence of cancer is ten 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 a trait controlled by a normal allele. These 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 be when the trait controlled by the pathological allele is of a different (new) quality compared to the trait controlled by the normal allele. Example: the 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 their effect on the structure protein product gene and/or the level of its expression.

Gene mutations are molecular changes in the structure of DNA that are not visible under a light microscope. Gene mutations include any changes in the molecular structure of DNA, regardless of their location and impact on viability. Some mutations have no effect on the structure and function of the corresponding protein. Another (most) part of gene mutations leads to the synthesis of a defective protein that is unable to perform its proper function. It is gene mutations that determine the development of most hereditary forms of pathology.

The most common monogenic diseases in humans are: cystic fibrosis, hemochromatosis, adrenogenital syndrome, phenylketonuria, neurofibromatosis, Duchenne-Becker myopathies and a number of other diseases. Clinically, they are manifested by signs of metabolic disorders (metabolism) in the body. The mutation may be:

1) in a base substitution in a codon, this is the so-called missense mutation(from English, mis - false, incorrect + lat. sensus - meaning) - a nucleotide substitution in the coding part of the gene, leading to an amino acid substitution in the polypeptide;

2) in such a change in codons, which will lead to a stop in reading information, this is the so-called nonsense mutation(from Latin non - no + sensus - meaning) - a nucleotide replacement in the coding part of the gene leads to the formation of a terminator codon (stop codon) and the termination of translation;

3) a violation of reading information, a shift in the reading frame, called frameshift(from the English frame - frame + shift: - shift, movement), when molecular changes in DNA lead to a change in triplets during the translation of the polypeptide chain.

Other types of gene mutations are also known. According to the type of molecular changes, there are:

division(from lat. deletio - destruction), when there is a loss of a DNA segment ranging in size from one nucleotide to a gene;

duplications(from lat. duplicatio - doubling), i.e. duplication or re-duplication of a DNA segment from one nucleotide to entire genes;

inversions(from lat. inversio - turning over), i.e. a 180° turn of a DNA segment ranging in size from two nucpeotides to a fragment that includes several genes;

insertions(from lat. insertio - attachment), i.e. insertion of DNA fragments ranging in size from one nucleotide to the whole gene.

Molecular changes affecting one to several nucleotides are considered as point mutations.

Fundamental and distinctive for a gene mutation is that it 1) leads to a change in genetic information, 2) can be transmitted from generation to generation.

A certain part of gene mutations can be classified as neutral mutations, since they do not lead to any changes in the phenotype. For example, due to the degeneracy of the genetic code, the same amino acid can be encoded by two triplets that differ only in one base. On the other hand, the same gene can change (mutate) into several different states.

For example, the gene that controls the blood group of the AB0 system. has three alleles: 0, A and B, combinations of which determine 4 blood groups. The AB0 blood group is a classic example of the genetic variability of normal human traits.

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

Genomic and chromosomal mutations

Genomic and chromosomal mutations are the causes of chromosomal diseases. Genomic mutations include aneuploidy and changes in the ploidy of structurally unchanged chromosomes. Detected by cytogenetic methods.

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

Polyploidy- 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, for the 21st pair, with Down syndrome, for the 18th pair for Edwards syndrome, for the 13th pair for Patau syndrome; for sex chromosomes: XXX, XXY, XYY);

monosomy- the presence of only one of the two homologous chromosomes. With monosomy for any of the autosomes, the normal development of the embryo is impossible. The only monosomy in humans that is compatible with life - monosomy on the X chromosome - leads (to Shereshevsky-Turner syndrome (45, X0).

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 lagging, when one of the homologous chromosomes can lag behind all other non-homologous chromosomes during the movement to the pole. The term "nondisjunction" means the absence of separation of chromosomes or chromatids in meiosis or mitosis. The loss of chromosomes can lead to mosaicism, in which there is one e uploid(normal) cell line, and the other monosomic.

Chromosome nondisjunction is most commonly observed during meiosis. Chromosomes, which normally divide during meiosis, remain attached together and move to one pole of the cell in anaphase. Thus, two gametes arise, 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 (that is, there are three homologous chromosomes in the cell), when a gamete without one chromosome is fertilized, a zygote with monosomy occurs. If a monosomal zygote is formed on any autosomal (non-sex) chromosome, then the development of the organism stops at the earliest stages of development.

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

Intrachromosomal mutations are aberrations within one chromosome. These include:

—deletions(from lat. deletio - destruction) - the loss of one of the sections of the chromosome, internal or terminal. This can lead to a violation of embryogenesis and the formation of multiple developmental anomalies (for example, division in the region of the short arm of the 5th chromosome, designated as 5p-, leads to underdevelopment of the larynx, heart defects, mental retardation). This symptom complex is known as the "cat's cry" syndrome, since in sick children, due to an anomaly of the larynx, crying resembles a cat's meow;

—inversions(from lat. inversio - turning over). As a result of two points of breaks in the chromosome, the resulting fragment is inserted into its original place after turning by 180°. As a result, only the order of the genes is violated;

— duplications(from Lat duplicatio - doubling) - doubling (or multiplication) of any part of the chromosome (for example, trisomy along one of the short arms of the 9th chromosome causes multiple defects, including microcephaly, delayed physical, mental and intellectual development).

Schemes of the most frequent chromosomal aberrations:
Division: 1 - terminal; 2 - interstitial. Inversions: 1 - pericentric (with capture of the centromere); 2 - paracentric (within one chromosome arm)

Interchromosomal mutations, or rearrangement mutations- exchange of fragments between non-homologous chromosomes. Such mutations are called translocations (from Latin tgans - for, through + locus - place). It:

Reciprocal translocation, when two chromosomes exchange their fragments;

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

- "centric" fusion (Robertsonian translocation) - the connection of two acrocentric chromosomes in the region of their centromeres with the loss of short arms.

With a transverse rupture of chromatids through the centromeres, "sister" chromatids become "mirror" arms of two different chromosomes containing the same sets of genes. Such chromosomes are called isochromosomes. Both intrachromosomal (deletions, inversions, and duplications) and interchromosomal (translocations) aberrations and isochromosomes are associated with physical changes structures of chromosomes, including those with mechanical breaks.

Hereditary pathology as a result of hereditary variability

The presence of common species characteristics makes it possible to unite all people on earth into a single species of Homo sapiens. Nevertheless, we can easily, with one glance, single out the face of a person we know in the crowd. strangers. The extraordinary diversity of people, both within a group (for example, diversity within an ethnic group) and between groups, is due to their genetic difference. It is now believed that all intraspecific variability is due to different genotypes that arise and are maintained by natural selection.

It is known that the human haploid genome contains 3.3x10 9 pairs of nucleotide residues, which theoretically allows to have up to 6-10 million genes. At the same time, the data of modern studies indicate that the human genome contains approximately 30-40 thousand genes. About a third of all genes have more than one allele, that is, they are polymorphic.

The concept of hereditary polymorphism was formulated by E. Ford in 1940 to explain the existence of two or more distinct forms in a population, when the frequency of the rarest of them cannot be explained only by mutational events. Since gene mutation is a rare event (1x10 6), the frequency of the mutant allele, which is more than 1%, can only be explained by its gradual accumulation in the population due to the selective advantages of the carriers of this mutation.

The multiplicity of splitting loci, the multiplicity of alleles in each of them, along with the phenomenon of recombination, creates an inexhaustible genetic diversity of man. Calculations show that in the entire history of mankind there has not been, is not and in the foreseeable future there will not be a genetic repetition on the globe, i.e. each person born is a unique phenomenon in the universe. The uniqueness of the genetic constitution largely determines the characteristics of the development of the disease in each individual person.

Humanity has evolved as groups of isolated populations living in the same conditions for a long time. environment, including climatic and geographical characteristics, the nature of nutrition, pathogens, cultural traditions, etc. This led to the fixation in the population of specific combinations of normal alleles for each of them, the most adequate to environmental conditions. In connection with the gradual expansion of the habitat, intensive migrations, resettlement of peoples, situations arise when combinations of specific normal genes that are useful under certain conditions in other conditions do not ensure the optimal functioning of some body systems. This leads to the fact that part of the hereditary variability, due to an unfavorable combination of non-pathological human genes, becomes the basis for the development of so-called diseases with a hereditary predisposition.

In addition, in humans, as a social being, natural selection proceeded over time in more and more specific forms, which also expanded hereditary diversity. What could be swept aside in animals was preserved, or, conversely, what animals saved was lost. Thus, the full satisfaction of the needs for vitamin C led in the process of evolution to the loss of the L-gulonodactone oxidase gene, which catalyzes the synthesis of ascorbic acid. In the process of evolution, humanity also acquired undesirable signs that are directly related to pathology. For example, in humans, in the process of evolution, genes appeared that determine sensitivity to diphtheria toxin or to the polio virus.

Thus, in humans, as in any other biological species, there is no sharp line between hereditary variability, leading to normal variations in traits, and hereditary variability, which causes the occurrence of hereditary diseases. Man, having become a biological species of Homo sapiens, as if paid for the "reasonableness" of his species by the accumulation of pathological mutations. This position underlies one of the main concepts of medical genetics about the evolutionary accumulation of pathological mutations in human populations.

The hereditary variability of human populations, both maintained and reduced by natural selection, forms the so-called genetic load.

Some pathological mutations can persist and spread in populations for a historically long time, causing the so-called segregation genetic load; other pathological mutations arise in each generation as a result of new changes in the hereditary structure, creating a mutation load.

The negative effect of the genetic load is manifested by increased mortality (death of gametes, zygotes, embryos and children), decreased fertility (reduced reproduction of offspring), reduced life expectancy, social disadaptation and disability, and also causes an increased need for medical care.

The English geneticist J. Hodden was the first to draw the attention of researchers to the existence of a genetic load, although the term itself was proposed by G. Meller back in the late 40s. The meaning of the concept of "genetic load" is associated with a high degree of genetic variability necessary for a biological species in order to be able to adapt to changing environmental conditions.

Mutation is understood change in the amount and structure of DNA in a cell or in an organism. In other words, mutation is a change in the genotype. A feature of the genotype change is that this change as a result of mitosis or meiosis can be transferred to the next generations of cells.

Most often, mutations are understood as a small change in the sequence of DNA nucleotides (changes in one gene). These are the so-called. However, in addition to them, there are also when changes affect large sections of DNA, or the number of chromosomes changes.

As a result of a mutation, a new trait may suddenly appear in an organism.

The idea that it is mutation that is the cause of the appearance of new traits transmitted through generations was first expressed by Hugh de Vries in 1901. Later, mutations in Drosophila were studied by T. Morgan and the staff of his school.

Mutation - harm or benefit?

Mutations that occur in "insignificant" ("silent") sections of DNA do not change the characteristics of the organism and can be easily passed on from generation to generation (natural selection will not act on them). Such mutations can be considered neutral. Mutations are also neutral when a gene segment is replaced with a synonymous one. In this case, although the nucleotide sequence in a certain area will be different, the same protein will be synthesized (with the same amino acid sequence).

However, a mutation can affect a significant gene, change the amino acid sequence of the synthesized protein, and, consequently, cause a change in the characteristics of the organism. Subsequently, if the concentration of a mutation in a population reaches a certain level, this will lead to a change characteristic feature the entire population.

In wildlife, mutations occur as errors in DNA, so all of them are a priori harmful. Most mutations reduce the viability of the organism, cause various diseases. Mutations that occur in somatic cells are not transmitted to the next generation, but as a result of mitosis, daughter cells are formed that make up a particular tissue. Often, somatic mutations lead to the formation of various tumors and other diseases.

Mutations that occur in germ cells can be passed on to the next generation. In stable environmental conditions, almost all changes in the genotype are harmful. But if environmental conditions change, it may turn out that a previously harmful mutation will become beneficial.

For example, a mutation that causes short wings in an insect is likely to be harmful in a population that lives in places where there is no strong wind. This mutation will be akin to deformity, disease. Insects with it will have difficulty finding mating partners. But if stronger winds begin to blow on the terrain (for example, a forest area was destroyed as a result of a fire), then insects with long wings will be blown away by the wind, it will be harder for them to move. Under such conditions, short-winged individuals can gain an advantage. They will find partners and food more often than long-winged ones. After some time, there will be more short-winged mutants in the population. Thus, the mutation will be fixed and become the norm.

Mutations underlie natural selection and this is their main benefit. For the body, the overwhelming number of mutations is harmful.

Why do mutations occur?

In nature, mutations occur randomly and spontaneously. That is, any gene can mutate at any time. However, the frequency of mutations in different organisms and cells is different. For example, it is related to the duration life cycle: the shorter it is, the more mutations occur. Thus, mutations occur much more frequently in bacteria than in eukaryotic organisms.

Except spontaneous mutations(happening naturally) are induced(by a person in laboratory conditions or adverse environmental conditions) mutations.

Basically, mutations occur as a result of errors in DNA replication (doubling), repair (restoration) of DNA, with unequal crossing over, improper chromosome segregation in meiosis, etc.

So in cells, the restoration (repair) of damaged DNA sections is constantly taking place. However, if as a result various reasons repair mechanisms are violated, then errors in the DNA will remain and accumulate.

The result of a replication error is the replacement of one nucleotide in the DNA chain with another.

What causes mutations?

Enhanced Level mutations causes x-rays, ultraviolet and gamma rays. Also, mutagens include α- and β-particles, neutrons, cosmic radiation (all these are high-energy particles).

Mutagen is something that can cause mutation.

In addition to various radiations, many chemical substances: formaldehyde, colchicine, tobacco ingredients, pesticides, preservatives, some medications and etc.

hereditary variability

Combination variability. Hereditary, or genotypic, variability is divided into combinative and mutational.

Variability is called combinative, which is based on the formation of recombinations, i.e. such combinations of genes that the parents did not have.

Combinative variability is based on sexual reproduction of organisms, as a result of which a huge variety of genotypes arises. Three processes serve as almost unlimited sources of genetic variability:

Independent divergence of homologous chromosomes in the first meiotic division. It is the independent combination of chromosomes during meiosis that is the basis of Mendel's third law. The appearance of green smooth and yellow wrinkled pea seeds in the second generation from crossing plants with yellow smooth and green wrinkled seeds is an example of combinative variability.

Mutual exchange of sections of homologous chromosomes, or crossing over (see Fig. 3.10). It creates new linkage groups, that is, it serves as an important source of genetic recombination of alleles. Recombinant chromosomes, once in the zygote, contribute to the appearance of signs that are atypical for each of the parents.

Random combination of gametes during fertilization.

These sources of combinative variability act independently and simultaneously, while providing a constant “shuffling” of genes, which leads to the emergence of organisms with different genotype and phenotype (the genes themselves do not change). However, new combinations of genes fall apart quite easily when passed from generation to generation.

Combinative variability is the most important source of all the colossal hereditary diversity characteristic of living organisms. However, the listed sources of variability do not give rise to stable changes in the genotype that are essential for survival, which are necessary, according to evolutionary theory, for the emergence of new species. Such changes result from mutations.

mutational variability. Mutational called the variability of the genotype itself. Mutations - these are sudden inherited changes in the genetic material, leading to a change in certain signs of the organism.

The main provisions of the mutation theory were developed by G. De Vries in 1901-1903. and boil down to the following:

Mutations occur suddenly, abruptly, as discrete changes in traits.

Unlike non-hereditary changes, mutations are qualitative changes that are passed down from generation to generation.

Mutations manifest themselves in different ways and can be both beneficial and harmful, both dominant and recessive.

The probability of detecting mutations depends on the number of individuals studied.

Similar mutations can occur repeatedly.

Mutations are non-directional (spontaneous), i.e., any part of the chromosome can mutate, causing changes in both minor and vital signs.

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. By the nature of the change genome, i.e. the totality of genes contained in the haploid set of chromosomes, distinguish gene, chromosomal and genomic mutations.

genetic, or point, mutation- the result of a change in the nucleotide sequence in a DNA molecule within a single gene. Such a change in the gene is reproduced during transcription in the structure of mRNA; it changes the sequence amino acids in the polypeptide chain formed during translation on ribosomes. As a result, another protein is synthesized, which leads to a change in the corresponding feature of the organism. This is the most common type of mutation and the most important source of hereditary variability in organisms.

There are different types of gene mutations associated with the addition, loss or rearrangement of nucleotides in the gene. it duplications(repetition of a section of a gene), inserts(the appearance in the sequence of an extra pair of nucleotides), deletions("loss of one or more base pairs") substitutions of nucleotide pairs (AT -> <- HZ; AT -> <- ; CG; or AT -> <- TA), inversions(reversal of the gene section by 180°).

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 of the newly emerging 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 organism and to manifest itself in the future when they pass into the homozygous state.

At the same time, a number of cases are known when a change in only one base in a particular gene has a noticeable effect on the phenotype. One example is a genetic anomaly like sickle cell anemia. The recessive allele that causes this hereditary disease in the homozygous state is expressed in the replacement of only one amino acid residue in ( B-chains 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 to crescent-shaped) and quickly destroyed. In this case, acute anemia develops and a decrease in the amount of oxygen carried by the blood is observed. Anemia causes physical weakness, impaired functioning of the heart and kidneys, and can lead to early death in people homozygous for the mutant allele.

Chromosomal mutations (rearrangements, or aberrations)- These are changes in the structure of chromosomes that can be identified and studied under a light microscope.

Known perestroika different types(Fig. 3.13):

a lack of, or deficiency,- loss of terminal sections of the chromosome;

deletion- loss of a chromosome segment in its middle part;

duplication - two- or multiple repetition of genes localized in a certain region of the chromosome;

inversion- rotation of a section of the chromosome by 180°, as a result of which the genes in this section are located in the reverse order compared to the usual one;

translocation- change in the position of any part of the chromosome in the chromosome set. The most common type of translocations are reciprocal, in which regions are exchanged between two non-homologous chromosomes. A segment of a chromosome can change its position even without reciprocal exchange, remaining in the same chromosome or being included in some other one.

At deficiencies, deletions and duplications the amount of genetic material changes. The degree of phenotypic change depends on how large the corresponding sections of chromosomes are and whether they contain important genes. Examples of deficiencies are known in many organisms, including humans. Severe hereditary disease -syndrome "cat's cry"(so named for the nature of the sounds made by sick babies), due to heterozygosity for deficiency in the 5th chromosome. This syndrome is accompanied by severe dysplasia and mental retardation. Usually children with this syndrome die early, but some live to adulthood.

3.13 . Chromosomal rearrangements that change the location of genes on chromosomes.

Genomic mutations- change in the number of chromosomes in the genome of body cells. This phenomenon occurs in two directions: towards an increase in the number of whole haploid sets (polyploidy) and towards the loss or inclusion of individual chromosomes (aneuploidy).

Polyploidy- multiple increase in the haploid set of chromosomes. Cells with different numbers of haploid sets of chromosomes are called triploid (3n), tetraploid (4n), hexanoid (6n), octaploid (8n), etc.

Most often, polyploids are formed when the order of divergence of chromosomes to the poles of the cell during meiosis or mitosis is violated. This can be caused by the action of physical and chemical factors. Chemicals such as colchicine inhibit the formation of the mitotic spindle in cells that have begun to divide, as a result of which the duplicated chromosomes do not diverge and the cell becomes tetragonal.

For many plants, the so-called polyploid lines. They include forms from 2 to 10n and more. For example, a polyploid row of sets of 12, 24, 36, 48, 60, 72, 96, 108 and 144 chromosomes are representatives of the genus Solanum (Solanum). The genus wheat (Triticum) is a series whose members have 34, 28 and 42 chromosomes.

Polyploidy results in a change in the traits of an organism and is therefore an important source of variability in evolution and selection, especially in plants. This is due to the fact that hermaphroditism (self-pollination), apomixis (parthenogenesis) and vegetative reproduction are very widespread in plant organisms. Therefore, about a third of plant species distributed on our planet are polyploids, and in the sharply continental conditions of the high-mountainous Pamirs, up to 85% of polyploids grow. Almost all cultivated plants are also polyploids, which, unlike their wild relatives, have larger flowers, fruits and seeds, and more nutrients accumulate in the storage organs (stem, tubers). Polyploids adapt more easily to adverse living conditions, more easily tolerate low temperatures and drought. That is why they are widespread in the northern and high mountain regions.

The sharp increase in the productivity of polyploid forms of cultivated plants is based on the phenomenon polymers(see § 3.3).

Aneuploidy or heteroplodia,- a phenomenon in which the cells of the body contain an altered number of chromosomes that is not a multiple of the haploid set. Aneuploids occur when individual homologous chromosomes do not diverge or are lost during mitosis and meiosis. As a result of nondisjunction of chromosomes during gametogenesis, germ cells with extra chromosomes can appear, and then, upon subsequent fusion with normal haploid gametes, they form a zygote 2n + 1 (trisomic) on a particular chromosome. If there is less than one chromosome in the gamete, then subsequent fertilization leads to the formation of a zygote 1n - 1 (monosomic) on any of the chromosomes. In addition, there are forms 2n - 2, or nullisomics, since there is no pair of homologous chromosomes, and 2n + X, or polysomy.

Aneuploids are found in both plants and animals, as well as in humans. Aneuploid plants have low viability and fertility, and in humans this phenomenon often leads to infertility and in these cases is not inherited. In children born to mothers over 38 years of age, the likelihood of aneuploidy is increased (up to 2.5%). In addition, cases of aneuploidy in humans cause chromosomal diseases.

In dioecious animals, both in natural and in artificial conditions, polyploidy is extremely rare. This is due to the fact that polyploidy, causing a change in the ratio of sex chromosomes and autosomes, leads to a violation of the conjugation of homologous chromosomes and thus makes it difficult to determine sex. As a result, such forms turn out to be fruitless and unviable.

Spontaneous and induced mutations. Spontaneous called mutations that occur under the influence of unknown natural factors, most often as a result of errors in the reproduction of genetic material (DNA or RNA). The frequency of spontaneous mutation in each species is genetically determined and maintained at a certain level.

induced mutagenesis- this is an artificial obtaining of mutations with the help of physical and chemical mutagens. Sharp increase mutation frequency (hundreds of times) occurs under the influence of all types of ionizing radiation (gamma and x-rays, protons, neutrons, etc.), ultraviolet radiation, high and low temperatures. Chemical mutagens include substances such as formalin, nitrogen mustard, colchicine, caffeine, some components of tobacco, drugs, food preservatives and pesticides. Biological mutagens are viruses and toxins of a number of mold fungi.

Currently, work is underway to create methods for the directed action of various mutagens on specific genes. Such studies are very important, since the artificial production of mutations in the desired genes can be of great practical importance for the selection of plants, animals, and microorganisms.

The law of homologous series in hereditary variability. The largest generalization of works on the study of variability at the beginning of the 20th century. became law of homologous series in hereditary variability. It was formulated by the outstanding Russian scientist N. I. Vavilov in 1920. The essence of the law is as follows: species and genera that are genetically close, related to each other by the unity of origin, are characterized by similar series of hereditary variability. Knowing what forms of variability are found in one species, one can foresee the occurrence of similar forms in a related species.

The law of homological series of phenotypic variability in related species is based on the idea of ​​the unity of their origin from one ancestor in the process of natural selection. Since common ancestors had a specific set of genes, their descendants should have approximately the same set.

Moreover, similar mutations arise in related species that have a common origin. This means that representatives of different families and classes of plants and animals with a similar set of genes can be found parallelism- homologous series of mutations according to morphological, physiological and biochemical characteristics and properties. Thus, similar mutations occur in different classes of vertebrates: albinism and lack of feathers in birds, albinism and hairlessness in mammals, hemophilia in many mammals and humans. In plants, hereditary variability has been noted for such traits as membranous or bare grain, awned or awnless ear, etc.

The law of homological series, reflecting the general regularity of the mutation process and morphogenesis of organisms, provides ample opportunities for its practical use in agricultural production, breeding, and medicine. Knowledge of the nature of variability of several related species makes it possible to search for a feature that is absent in one of them, but is characteristic of others. In this way, naked forms of cereals, one-seeded varieties of sugar beet, which do not need to be broken, were collected and studied, which is especially important in mechanized soil cultivation. Medical science has been able to use animals with homologous diseases as models for the study of human diseases: these are diabetes rats; congenital deafness of mice, dogs, guinea pigs; cataracts in the eyes of mice, rats, dogs, etc.

The law of homological series also makes it possible to foresee the possibility of the appearance of mutations still unknown to science, which can be used in breeding to create new forms valuable for the economy.

Mutation types

It is likely that the fruit flies that Muller irradiated had many more mutations than he could detect. By definition, a mutation is any change in DNA. This means that mutations can occur anywhere in the genome. And since most of the genome is occupied by “junk” DNA that does not code for anything, most mutations go unnoticed.

Mutations change physical properties organism (traits) only if they change the DNA sequence within the gene (Fig. 7.1).

Rice. 7.1. These three amino acid sequences show how small changes can make a big difference. The beginning of one of the amino acid chains in a normal protein is shown in the top row. Below is the amino acid chain of an abnormal variant of the hemoglobin protein: valine is replaced by glutamic acid in the sixth position. This single substitution, which mutates the GAA codon to the GUA codon, is the cause of sickle cell anemia, with symptoms ranging from mild anemia (if the individual has a normal copy of the mutated gene) to death (if the individual has two mutated copies of the gene)

Although Muller induced mutations in fruit flies by exposing them to high doses of radiation, mutations happen all the time in the body. Sometimes these are simply errors of normal processes occurring in the cell, and sometimes they are the result of environmental influences. Such spontaneous mutations occur at frequencies characteristic of a particular organism, sometimes referred to as the spontaneous background.

The most common point mutations occur, which change just one base pair in the normal DNA sequence. They can be obtained in two ways:

1. DNA is chemically modified so that one base changes to another. 2. DNA replication works with errors, inserting the wrong base into the strand during DNA synthesis.

Whatever the reason for their appearance, point mutations can be divided into two types:

1. Transitions. The most common type of mutation. In transition, one pyrimidine is replaced by another pyrimidine, or one purine is replaced by another purine: for example, a G-C pair becomes an A-T pair, or vice versa.

2. Transversions. A rarer type of mutation. Purine is replaced by pyrimidine or vice versa: for example, couple A-T becomes a pair of T-A or C-G.

Nitrous acid is a mutagen that causes transitions. It converts cytosine to uracil. Cytosine usually pairs with guanine, but uracil pairs with adenine. As a result couple C-G becomes a T-A pair when A pairs with T in the next replication. Nitrous acid has the same effect on adenine, turning the A-T pair into a C-G pair.

Another reason for transitions is mismatch grounds. This happens when, for some reason, the wrong base is inserted into a strand of DNA, then it pairs with the wrong partner (non-complementary base) instead of the one it should pair with. As a result, during the next replication cycle, the pair completely changes.

The effect of point mutations depends on where in the base sequence they are formed. Since a change in one base pair only changes one codon, and therefore one amino acid, the resulting protein may be damaged, but may retain some of its normal activity despite the damage.

Much stronger than point mutations damage DNA frameshift mutations. Recall that the genetic base sequence (sequence) is read as a sequence of non-overlapping triplets (three bases). This means that there are three ways of reading (reading frames) of a sequence of bases, depending on the starting point of reading. If a mutation removes or inserts an extra base, it causes a frame shift and the entire base sequence is misread. This means that the entire sequence of amino acids will change, and the resulting protein, with a high degree of probability, will be completely inoperative.

Frameshift mutations are caused acridines, chemicals that bind to DNA and change its structure so much that bases can be added to or removed from the DNA as it replicates. The effect of such mutations depends on the location of the base sequence at which the insertion will occur ( insertion) or dropout ( deletion) bases, as well as their relative position in the resulting sequence (Fig. 7.2).

Rice. 7.2. One of the ways in which a frameshift mutation can affect the reading of the DNA base sequence

Another type of mutation is the insertion (insertion) of long fragments of additional genetic material into the genome. Embedded transposing (mobile genetic) elements, or transposons, are sequences that can move from one DNA site to another. Transposons were first discovered by geneticist Barbara McClintock in the 1950s. These are short DNA elements that can jump from one point in the genome to another (which is why they are often called "jumping genes"). Sometimes they take with them nearby DNA sequences. Typically, transposons consist of one or more genes, one of which is an enzyme gene. transposases. This enzyme is required by transposons to move from one DNA site to another within the cell.

There are also retrotransposons, or retroposons who cannot move on their own. Instead, they use their mRNA. It is first copied into DNA, and the latter is inserted at another point in the genome. Retrotransposons are related to retroviruses.

If a transposon is inserted into a gene, the base coding sequence is disrupted and the gene is turned off in most cases. Transposons can also carry transcriptional or translational termination signals that effectively block the expression of other genes downstream. Such an effect is called polar mutation.

Retrotransposons are typical of mammalian genomes. In fact, about 40% of the genome consists of such sequences. This is one of the reasons why the genome contains so much "junk" DNA. Retrotransposons can be SINEs (short intermediate elements) several hundred base pairs long or LINEs (long intermediate elements) 3000 to 8000 base pairs long. For example, the human genome contains about 300,000 sequences of one type of SINE, which seem to have no other function than self-replication. These elements are also called "selfish" DNA.

Unlike point mutations, mutations caused by transposons cannot be induced by mutagens.

Point mutations can reverse, return to the original sequence, both by restoring the original DNA sequence, and by mutations in other places of the gene that compensate for the effect of the primary mutation.

The insertion of an additional DNA element, obviously, can reverse by cutting out the inserted material - point exclusion. Deletion of part of the gene, however, cannot reverse.

Mutations can occur in other genes, leading to the formation of a bypass that corrects the damage caused by the initial mutation. The result is a double mutant with a normal or nearly normal phenotype. This phenomenon is called suppression, which is of two types: extragenic and intragenic.

Extragene suppressor mutation suppresses the action of a mutation located in another gene, sometimes by changing the physiological conditions under which the protein encoded by the suppressed mutant can function again. It happens that such a mutation changes the amino acid sequence of the mutant protein.

Intragenic suppressor mutation suppresses the effect of the mutation in the gene where it is located, sometimes restoring the reading frame broken by the frameshift mutation. In some cases, the mutation changes amino acids at a site that compensates for the amino acid change caused by the primary mutation. The phenomenon is also called reversion in the second site.

Not all base sequences in a gene are equally mutable. Mutations tend to cluster around hotspots in the gene sequence - places where the probability of generating mutations is 10 or 100 times higher than expected in a random distribution. The location of these hot spots is different for different types of mutations and mutagens that induce them.

in bacteria E. coli, for example, hotspots occur where modified bases called 5-methylcytosine are located. This reason is sometimes undergoes a tautomeric shift- rearrangement of the hydrogen atom. As a result, G pairs with T instead of C, and after replication, a wild-type G-C pair and a mutant A-T pair are formed (in genetics wild type called DNA sequences that are commonly found in nature).

Many mutations have no visible effect. They're called silent mutations. Sometimes the mutation is silent because the change does not affect the production of amino acids, and sometimes because, despite the replacement of the amino acid in the protein, the new amino acid does not affect its function. It is called neutral replacement.

A mutation that turns off or changes the function of a gene is called direct mutation. A mutation that reactivates or restores the function of a gene by reversing the original mutation or by opening a bypass (as in the reversal at the second site described above) is called back mutation.

As you can see, there are many different ways to classify mutations, and the same mutation can be of different types. Table data. 7.1 can clarify the characterization of mutations.

Mutation classification

Mutation classification (continued)