The author of the article is L.V. Okolnova.

X-Men immediately come to mind... or Spider-Man...

But this is the case in cinema, in biology, too, but a little more scientific, less fantastic and more ordinary.

Mutation(in translation - change) - a stable, inherited change in DNA that occurs under the influence of external or internal changes.

Mutagenesis- the process of the appearance of mutations.

The common thing is that these changes (mutations) occur in nature and in humans constantly, almost every day.

First of all, mutations are divided into somatic- occur in the cells of the body, and generative- appear only in gametes.

Let us first analyze the types of generative mutations.

Gene mutations

What is a gene? This is a section of DNA (i.e., several nucleotides), respectively, this is a section of RNA, and a section of a protein, and some sign of an organism.

Those. gene mutation is a loss, replacement, insertion, doubling, change in the sequence of DNA sections.

In general, this does not always lead to illness. For example, when DNA is duplicated, such “mistakes” occur. But they rarely occur, this is a very small percentage of the total, so they are insignificant, which practically do not affect the body.

There are also serious mutagenesis:
- sickle cell anemia in humans;
- phenylketonuria - a metabolic disorder that causes quite serious mental retardation
- hemophilia
- gigantism in plants

Genomic mutations

Here is the classic definition of the term “genome”:

Genome -

The totality of hereditary material contained in the cell of the body;
- the human genome and the genomes of all other cellular life forms are built from DNA;
- the totality of the genetic material of the haploid set of chromosomes of a given species in pairs of DNA nucleotides per haploid genome.

To understand the essence, we greatly simplify, we get the following definition:

Genome is the number of chromosomes

Genomic mutations- change in the number of chromosomes of the body. Basically, their cause is a non-standard divergence of chromosomes in the process of division.

Down syndrome - normally a person has 46 chromosomes (23 pairs), however, with this mutation, 47 chromosomes are formed
rice. down syndrome

Polyploidy in plants (for plants this is generally the norm - most cultivated plants are polyploid mutants)

Chromosomal mutations- deformation of the chromosomes themselves.

Examples (most people have some rearrangements of this kind and generally do not affect their appearance or health in any way, but there are also unpleasant mutations):
- feline crying syndrome in a child
- developmental delay
etc.

Cytoplasmic mutations- mutations in the DNA of mitochondria and chloroplasts.

There are 2 organelles with their own DNA (circular, while the nucleus has a double helix) - mitochondria and plant plastids.

Accordingly, there are mutations caused by changes in these structures.

There is an interesting feature - this type of mutation is transmitted only by the female sex, because. during the formation of a zygote, only maternal mitochondria remain, and the “male” ones fall off with a tail during fertilization.

Examples:
- in humans - a certain form of diabetes mellitus, tunnel vision;
- in plants - variegation.

somatic mutations.

These are all the types described above, but they arise in the cells of the body (in somatic cells).
Mutant cells are usually much smaller than normal cells and are suppressed by healthy cells. (If not suppressed, then the body will be reborn or get sick).

Examples:
- Drosophila eyes are red, but may have white facets
- in a plant, this can be a whole shoot, different from others (I.V. Michurin thus bred new varieties of apples).

Cancer cells in humans

Examples of exam questions:

Down syndrome is the result of a mutation

1)) genomic;

2) cytoplasmic;

3) chromosomal;

4) recessive.

Gene mutations are associated with a change

A) the number of chromosomes in cells;

B) structures of chromosomes;

B) the sequence of genes in the autosome;

D) nucleoside in a DNA region.

Mutations associated with the exchange of regions of non-homologous chromosomes are referred to as

A) chromosomal;

B) genomic;

B) point;

D) gene.

An animal in whose offspring a trait due to a somatic mutation may appear

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 diverse. 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.

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 an extra chromosome, trisomy occurs (i.e., there are three homologous chromosomes in the cell), when a gamete without one chromosome is fertilized, a zygote with monosomy occurs. If a monosomic zygote is formed on any autosomal chromosome, then the development of the organism stops at the earliest stages of development.

According to the type of inheritance 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 of the reproductive cycle, but also the dominance of the mutant allele.

Direct mutations? these are mutations that inactivate wild-type genes, i.e. mutations that change the information encoded in DNA in a direct way, resulting in a change from 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.

In general, suppression can be:

? intragenic? when a second mutation in an already affected gene changes a codon defective as a result of a direct mutation in such a way that an amino acid is inserted into the polypeptide that can restore the functional activity of this protein. 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 of natural processes occurring in cells, occur in the natural radioactive background of the Earth 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 of the protein gene product and/or the level of its expression.

For genetic research, a person is an inconvenient object, since in a person: experimental crossing is impossible; a large number of chromosomes; puberty comes late; a small number of descendants in each family; equalization of living conditions for offspring is impossible.

A number of research methods are used in human genetics.

genealogical method

The use of this method is possible in the case when direct relatives are known - the ancestors of the owner of the hereditary trait ( proband) on the maternal and paternal lines in a number of generations or the descendants of the proband also in several generations. When compiling pedigrees in genetics, a certain system of notation is used. After compiling the pedigree, its analysis is carried out in order to establish the nature of the inheritance of the trait under study.

Conventions adopted in the preparation of pedigrees:
1 - man; 2 - woman; 3 - gender not clear; 4 - the owner of the studied trait; 5 - heterozygous carrier of the studied recessive gene; 6 - marriage; 7 - marriage of a man with two women; 8 - related marriage; 9 - parents, children and the order of their birth; 10 - dizygotic twins; 11 - monozygotic twins.

Thanks to the genealogical method, the types of inheritance of many traits in humans have been determined. So, according to the autosomal dominant type, polydactyly (an increased number of fingers), the ability to roll the tongue into a tube, brachydactyly (short fingers due to the absence of two phalanges on the fingers), freckles, early baldness, fused fingers, cleft lip, cleft palate, cataracts of the eyes, fragility of bones and many others. Albinism, red hair, susceptibility to polio, diabetes mellitus, congenital deafness, and other traits are inherited as autosomal recessive.

The dominant trait is the ability to roll the tongue into a tube (1) and its recessive allele is the absence of this ability (2).
3 - pedigree for polydactyly (autosomal dominant inheritance).

A number of traits are inherited sex-linked: X-linked inheritance - hemophilia, color blindness; Y-linked - hypertrichosis of the edge of the auricle, webbed toes. There are a number of genes located in homologous regions of the X and Y chromosomes, such as general color blindness.

The use of the genealogical method showed that in a related marriage, compared with an unrelated one, the likelihood of deformities, stillbirths, and early mortality in the offspring increases significantly. In related marriages, recessive genes often go into a homozygous state, as a result, certain anomalies develop. An example of this is the inheritance of hemophilia in the royal houses of Europe.

- hemophilic; - carrier woman

twin method

1 - monozygotic twins; 2 - dizygotic twins.

Children born at the same time are called twins. They are monozygotic(identical) and dizygotic(variegated).

Monozygotic twins develop from one zygote (1), which is divided into two (or more) parts during the crushing stage. Therefore, such twins are genetically identical and always of the same sex. Monozygotic twins are characterized by a high degree of similarity ( concordance) in many ways.

Dizygotic twins develop from two or more eggs that are simultaneously ovulated and fertilized by different spermatozoa (2). Therefore, they have different genotypes and can be either the same or different sex. Unlike monozygotic twins, dizygotic twins are characterized by discordance - dissimilarity in many ways. Data on the concordance of twins for some signs are given in the table.

signs	Concordance, %
	Monozygotic twins	dizygotic twins
Normal
Blood group (AB0)	100	46
eye color	99,5	28
Hair color	97	23
Pathological
Clubfoot	32	3
"Hare Lip"	33	5
Bronchial asthma	19	4,8
Measles	98	94
Tuberculosis	37	15
Epilepsy	67	3
Schizophrenia	70	13

As can be seen from the table, the degree of concordance of monozygotic twins for all the above characteristics is significantly higher than that of dizygotic twins, but it is not absolute. As a rule, the discordance of monozygotic twins occurs as a result of intrauterine development disorders of one of them or under the influence of the external environment, if it was different.

Thanks to the twin method, a person's hereditary predisposition to a number of diseases was clarified: schizophrenia, epilepsy, diabetes mellitus and others.

Observations on monozygotic twins provide material for elucidating the role of heredity and environment in the development of traits. Moreover, the external environment is understood not only as physical factors of the environment, but also as social conditions.

Cytogenetic method

Based on the study of human chromosomes in normal and pathological conditions. Normally, a human karyotype includes 46 chromosomes - 22 pairs of autosomes and two sex chromosomes. The use of this method made it possible to identify a group of diseases associated either with a change in the number of chromosomes or with changes in their structure. Such diseases are called chromosomal.

Blood lymphocytes are the most common material for karyotypic analysis. Blood is taken in adults from a vein, in newborns - from a finger, earlobe or heel. Lymphocytes are cultivated in a special nutrient medium, which, in particular, contains substances that “force” lymphocytes to intensively divide by mitosis. After some time, colchicine is added to the cell culture. Colchicine stops mitosis at the metaphase level. It is during metaphase that the chromosomes are most condensed. Next, the cells are transferred to glass slides, dried and stained with various dyes. Coloring can be a) routine (chromosomes stain evenly), b) differential (chromosomes acquire transverse striation, with each chromosome having an individual pattern). Routine staining allows you to identify genomic mutations, determine the group belonging of the chromosome, and find out in which group the number of chromosomes has changed. Differential staining allows you to identify chromosomal mutations, determine the chromosome to the number, find out the type of chromosomal mutation.

In cases where it is necessary to conduct a karyotypic analysis of the fetus, cells of the amniotic (amniotic) fluid are taken for cultivation - a mixture of fibroblast-like and epithelial cells.

Chromosomal diseases include: Klinefelter syndrome, Turner-Shereshevsky syndrome, Down syndrome, Patau syndrome, Edwards syndrome and others.

Patients with Klinefelter's syndrome (47, XXY) are always male. They are characterized by underdevelopment of the sex glands, degeneration of the seminiferous tubules, often mental retardation, high growth (due to disproportionately long legs).

Turner-Shereshevsky syndrome (45, X0) is observed in women. It manifests itself in slowing down puberty, underdevelopment of the gonads, amenorrhea (absence of menstruation), infertility. Women with Turner-Shereshevsky syndrome are small in stature, the body is disproportionate - the upper body is more developed, the shoulders are wide, the pelvis is narrow - the lower limbs are shortened, the neck is short with folds, the “Mongoloid” eye shape and a number of other signs.

Down syndrome is one of the most common chromosomal diseases. It develops as a result of trisomy on chromosome 21 (47; 21, 21, 21). The disease is easily diagnosed, as it has a number of characteristic features: shortened limbs, a small skull, a flat, wide nose, narrow palpebral fissures with an oblique incision, the presence of a fold of the upper eyelid, and mental retardation. Violations of the structure of internal organs are often observed.

Chromosomal diseases also occur as a result of changes in the chromosomes themselves. Yes, deletion R-arm of autosome number 5 leads to the development of the "cat's cry" syndrome. In children with this syndrome, the structure of the larynx is disturbed, and in early childhood they have a kind of “meowing” voice timbre. In addition, there is a retardation of psychomotor development and dementia.

Most often, chromosomal diseases are the result of mutations that have occurred in the germ cells of one of the parents.

Biochemical method

Allows you to detect metabolic disorders caused by changes in genes and, as a result, changes in the activity of various enzymes. Hereditary metabolic diseases are divided into diseases of carbohydrate metabolism (diabetes mellitus), metabolism of amino acids, lipids, minerals, etc.

Phenylketonuria refers to diseases of amino acid metabolism. The conversion of the essential amino acid phenylalanine to tyrosine is blocked, while phenylalanine is converted to phenylpyruvic acid, which is excreted in the urine. The disease leads to the rapid development of dementia in children. Early diagnosis and diet can stop the development of the disease.

Population-statistical method

It is a method of studying the distribution of hereditary traits (inherited diseases) in populations. An essential point when using this method is the statistical processing of the obtained data. Under population understand the totality of individuals of the same species, living in a certain territory for a long time, freely interbreeding with each other, having a common origin, a certain genetic structure and, to one degree or another, isolated from other such populations of individuals of a given species. A population is not only a form of existence of a species, but also a unit of evolution, since the basis of microevolutionary processes culminating in the formation of a species are genetic transformations in populations.

The study of the genetic structure of populations deals with a special section of genetics - population genetics. In humans, three types of populations are distinguished: 1) panmictic, 2) demes, 3) isolates, which differ from each other in number, frequency of intra-group marriages, the proportion of immigrants, and population growth. The population of a large city corresponds to the panmictic population. The genetic characteristics of any population includes the following indicators: 1) gene pool(the totality of genotypes of all individuals of a population), 2) gene frequencies, 3) genotype frequencies, 4) phenotype frequencies, marriage system, 5) factors that change gene frequencies.

To determine the frequencies of occurrence of certain genes and genotypes, hardy-weinberg law.

Hardy-Weinberg law

In an ideal population, from generation to generation, a strictly defined ratio of frequencies of dominant and recessive genes (1), as well as the ratio of frequencies of genotypic classes of individuals (2) is preserved.

p + q = 1, (1)
R 2 + 2pq + q 2 = 1, (2)

where p— frequency of occurrence of the dominant gene A; q- the frequency of occurrence of the recessive gene a; R 2 - the frequency of occurrence of homozygotes for the dominant AA; 2 pq- frequency of occurrence of Aa heterozygotes; q 2 - the frequency of occurrence of homozygotes for the recessive aa.

The ideal population is a sufficiently large, panmictic (panmixia - free crossing) population, in which there is no mutation process, natural selection and other factors that disturb the balance of genes. It is clear that ideal populations do not exist in nature; in real populations, the Hardy-Weinberg law is used with amendments.

The Hardy-Weinberg law, in particular, is used to roughly count the carriers of recessive genes for hereditary diseases. For example, phenylketonuria is known to occur at a rate of 1:10,000 in a given population. Phenylketonuria is inherited in an autosomal recessive manner, therefore, patients with phenylketonuria have the aa genotype, that is q 2 = 0.0001. From here: q = 0,01; p= 1 - 0.01 = 0.99. Carriers of the recessive gene have the Aa genotype, that is, they are heterozygotes. The frequency of occurrence of heterozygotes (2 pq) is 2 0.99 0.01 ≈ 0.02. Conclusion: in this population, about 2% of the population are carriers of the phenylketonuria gene. At the same time, you can calculate the frequency of occurrence of homozygotes for the dominant (AA): p 2 = 0.992, just under 98%.

A change in the balance of genotypes and alleles in a panmictic population occurs under the influence of constantly acting factors, which include: the mutation process, population waves, isolation, natural selection, gene drift, emigration, immigration, inbreeding. It is thanks to these phenomena that an elementary evolutionary phenomenon arises - a change in the genetic composition of a population, which is the initial stage in the process of speciation.

Human genetics is one of the most intensively developing branches of science. It is the theoretical basis of medicine, reveals the biological basis of hereditary diseases. Knowing the genetic nature of diseases allows you to make an accurate diagnosis in time and carry out the necessary treatment.

Go to lectures №21"Variability"

There are various methods to detect genetic mutations. Southern blotting described above is used to detect large genomic mutations. Other methods use PCR-amplified or cloned DNA. Mutations can be detected directly by sequencing (determining the primary structure of DNA macromolecules) or using radioisotope and fluorescent systems.

They can also be identified by comparing the sequence tumor DNA with DNA isolated from normal tissues, or by comparison with the normal DNA sequence described in the literature (for example, in databases posted on the Internet).

Analysis of conformational polymorphism single stranded- a radioisotope method for determining mutations, based on a change in the shape (conformation) of mutant DNA, which can be detected by electrophoresis. To do this, normal and tumor DNA is cloned by PCR, denatured and examined using gel electrophoresis. The mutant DNA changes its conformation to a non-normal shape and acquires non-normal mobility on electrophoresis.

These changes are easily identified when radioautographs. The figure below illustrates the technique for analyzing the conformational polymorphism of single-stranded (single-stranded) DNA.

Denatured high performance liquid chromatography- a new method for detecting mutations that does not require the use of radioactive substances. In this study, normal and tumor DNA are amplified (cloned) by PCR, mixed and denatured to form a mixture of single-stranded DNA molecules. Then slow annealing is carried out, as a result of which double-stranded DNA is formed again.

When pairing the thread normal DNA with the tumor thread at the site of the mutation, mating is disturbed - the so-called heteroduplex. This heteroduplex has a melting point that differs from that of normal and tumor DNA, i.e., homoduplex molecules, and due to this it can be easily determined using chromatography.

Other detection methods mutations- denaturing gradient gel electrophoresis, allele-specific oligonucleotide analysis and allele-specific amplification - based on the detection of differences in the sequences of normal and tumor DNA.

Each of these methods(with the exception of direct sequencing) is a means of screening for the presence of a mutation, but does not determine its type or the nature of the sequence disorder. Currently, instruments and methods have been developed that allow us to study large fragments of the genome and exponentially increase our ability to detect mutations.

These include molecular genetic analysis of DNA(microarray analysis) using gene chips, or biochips, and the transgenomic WAVE DNA Fragmentation Analysis System, developed in California by Transgenomic.

Analysis of the conformation of single-stranded DNA.
Left - normal alleles have the same sequence and, accordingly, the same conformation, form two identical stripes.
The mutant allele is shown on the right. The dark and light segments have a slightly different sequence and, therefore, migrate in the gel at different rates.
As a result, four stripes are formed. This technique is sensitive for detecting differences of several base pairs.

The most significant changes in the genetic apparatus occur during genomic mutations, i.e. when the number of chromosomes in the set changes. They can concern either individual chromosomes ( aneuploidy), or whole genomes ( euploidy).

In animals, the main diploid the level of ploidy, which is associated with the predominance of their sexual mode of reproduction. Polyploidy in animals it is extremely rare, for example, in roundworms and rotifers. haploidy at the organismal level, it is also rare in animals (for example, drones in bees). Haploid are the germ cells of animals, which has a deep biological meaning: due to the change in nuclear phases, the optimal level of ploidy is stabilized - diploid. The haploid number of chromosomes is called the base number of chromosomes.

In plants, haploids spontaneously arise in populations at a low frequency (maize has 1 haploid per 1000 diploids). The phenotypic features of haploids are determined by two factors: external similarity with the corresponding diploids, from which they differ in smaller sizes, and the manifestation of recessive genes that are in their homozygous state. Haploids are usually sterile, because they lack homologous chromosomes and meiosis cannot proceed normally. Fertile gametes in haploids can be formed in the following cases: a) when chromosomes diverge in meiosis according to type 0- n(i.e. the entire haploid set of chromosomes goes to one pole); b) with spontaneous diploidization of germ cells. Their fusion leads to the formation of diploid offspring.

Many plants have a wide range of ploidy levels. For example, within the genus Poa (bluegrass), the number of chromosomes ranges from 14 to 256, i.e. basic number of chromosomes ( n= 7) increases by several tens of times. However, not all chromosome numbers are optimal and ensure the normal viability of individuals. There are biologically optimal and evolutionarily optimal levels of ploidy. In sexual species, they usually coincide (diploidy). In facultatively apomictic species, the evolutionary optimal is often the tetraploid level, which allows for the possibility of a combination of sexual reproduction and apomixis (i.e., parthenogenesis). It is the presence of an apomictic form of reproduction that explains the wide distribution of polyploidy in plants, since. in sexual species, polyploidy usually leads to sterility due to disturbances in meiosis, while in apomicts, meiosis does not occur during gamete formation, and they are often polyploid.

In some plant genera, the species form polyploid series with chromosome numbers that are multiples of the base number. For example, such a series exists in wheat: Triticum monococcum 2 n= 14 (einkorn wheat); Tr. durum 2 n= 28 (durum wheat); Tr. aestivum 2 n= 42 (soft wheat).

Distinguish between autopolyploidy and allopolyploidy.

Autopolyploidy

Autopolyploidy is an increase in the number of haploid sets of chromosomes of one species. The first mutant, an autotetraploid, was described at the beginning of the 20th century. G. de Vries at evening primrose. It had 14 pairs of chromosomes instead of 7. Further study of the number of chromosomes in representatives of different families revealed the wide distribution of autopolyploidy in the plant world. With autopolyploidy, either an even (tetraploids, hexaploids) or odd (triploids, pentaploids) increase in chromosome sets occurs. Autopolyploids differ from diploids in the larger size of all organs, including reproductive ones. This is based on an increase in cell size with increasing ploidy (nuclear plasma index).

Plants react differently to an increase in the number of chromosomes. If, as a result of polyploidy, the number of chromosomes becomes higher than optimal, then autopolyploids, showing individual signs of gigantism, are generally less developed, as, for example, 84-chromosomal wheat. Autopolyploids often exhibit some degree of sterility due to disruptions in meiosis during the maturation of germ cells. Sometimes highly polyploid forms generally turn out to be unviable and sterile.

Autopolyploidy is the result of a disruption in the process of cell division (mitosis or meiosis). Mitotic polyploidy results from nondisjunction of daughter chromosomes in prophase. If it occurs during the first division of the zygote, then all cells of the embryo will be polyploid; if at later stages, then somatic mosaics are formed - organisms whose body parts consist of polyploid cells. Mitotic polyploidization of somatic cells can occur at different stages of ontogeny. Meiotic polyploidy is observed when meiosis is lost or replaced by mitosis or some other type of non-reductive division during the formation of germ cells. Its result is the formation of unreduced gametes, the fusion of which leads to the appearance of polyploid offspring. Such gametes are most often formed in apomictic species, and as an exception in sexual species.

Very often, autotetraploids do not interbreed with the diploids from which they are descended. If the crossing between them still succeeds, then as a result, autotriploids arise. Odd polyploids, as a rule, are highly sterile and are not capable of seed reproduction. But for some plants, triploidy appears to be the optimum level of ploidy. Such plants show signs of gigantism compared to diploids. Examples are triploid aspen, triploid sugar beet, some varieties of apple trees. Reproduction of triploid forms is carried out either through apomixis or through vegetative reproduction.

For the artificial production of polyploid cells, a strong poison is used - colchicine, obtained from the autumn colchicum plant (Colchicum automnale). Its action is truly universal: you can get polyploids from any plant.

Allopolyploidy

Allopolyploidy- this is a doubling of the set of chromosomes in distant hybrids. For example, if a hybrid has two different AB genomes, then the polyploid genome will be AABB. Interspecific hybrids often turn out to be sterile, even if the species taken for crossing have the same chromosome numbers. This is explained by the fact that the chromosomes of different species are not homologous, and therefore the processes of conjugation and divergence of chromosomes are disturbed. Violations are even more pronounced when the numbers of chromosomes do not match. If the hybrid spontaneously duplicates the chromosomes in the egg, then an allopolyploid containing two diploid sets of parental species will be obtained. In this case, meiosis proceeds normally, and the plant will be fertile. Similar allopolyploids S.G. Navashin proposed calling them amphidiploids.

It is now known that many naturally occurring polyploid forms are allopolyploidy, for example, 42-chromosome common wheat is an amphidiploid that arose from crossing a tetraploid wheat and a diploid related species of Aegilops (Aegilops L.) followed by doubling the set of chromosomes of a triploid hybrid .

The allopolyploid nature has been established in a number of cultivated plant species, such as tobacco, rape, onion, willow, etc. Thus, allopolyploidy in plants is, along with hybridization, one of the mechanisms of speciation.

Aneuploidy

Aneuploidy denote a change in the number of individual chromosomes in the karyotype. The occurrence of aneuploids is a consequence of improper divergence of chromosomes in the process of cell division. Aneuploids often arise in the offspring of autopolyploids, which, due to incorrect divergence of multivalents, give rise to gametes with abnormal numbers of chromosomes. As a result of their merger, aneuploids arise. If one gamete has a set of chromosomes n+ 1, and the other - n, then from their merger, trisomic- diploid with one extra chromosome in the set. If a gamete with a set of chromosomes n- 1 merges with normal ( n), then it is formed monosomic A diploid with a lack of one chromosome. If two homologous chromosomes are missing in the set, then such an organism is called nullisomic. In plants, both monosomic and trisomic are often viable, although the loss or addition of one chromosome causes certain changes in the phenotype. The effect of aneuploidy depends on the number of chromosomes and the genetic makeup of the extra or missing chromosome. The more chromosomes in a set, the less sensitive plants are to aneuploidy. Trisomics in plants are somewhat less viable than normal individuals, and their fertility is reduced.

Monosomes in cultivated plants, such as wheat, are widely used in genetic analysis to determine the localization of various genes. In wheat, as well as in tobacco and other plants, monosomic series have been created, consisting of lines, in each of which some chromosome of the normal set has been lost. Nullisomics with 40 chromosomes (instead of 42) are also known in wheat. Their viability and fertility are reduced depending on which of the 21st pair of chromosomes is missing.

Aneuploidy in plants is closely related to polyploidy. This is clearly seen in the example of bluegrass. Within the genus Roa, species are known that make up polyploid series with chromosome numbers that are multiples of one basic number ( n= 7): 14, 28, 42, 56. In meadow grass meadow, euploidy is almost lost and replaced by aneuploidy. The number of chromosomes in different biotypes of this species varies from 50 to 100 and is not a multiple of the main number, which is associated with aneuploidy. Aneuploid forms are preserved due to the fact that they reproduce parthenogenetically. According to geneticists, aneuploidy is one of the mechanisms of genome evolution in plants.

In animals and humans, a change in the number of chromosomes has much more serious consequences. An example of monosomy is Drosophila with a deficiency of the 4th chromosome. It is the smallest chromosome in the set, but it contains the nucleolar organizer and therefore forms the nucleolus. Its absence causes a decrease in the size of flies, a decrease in fertility, and a change in a number of morphological characters. However, the flies are viable. The loss of one homologue from other pairs of chromosomes has a lethal effect.

In humans, genomic mutations usually lead to severe hereditary diseases. So, monosomy on the X chromosome leads to Shereshevsky-Turner syndrome, which is characterized by physical, mental and sexual underdevelopment of carriers of this mutation. A trisomy on the X chromosome has a similar effect. The presence of an extra 21st chromosome in the karyotype leads to the development of the well-known Down syndrome. (More details are given in the lecture “