A mutation is a change in the genome. Main types and examples

How do harmful genes arise?

Although the main property of genes is accurate self-copying, due to which the hereditary transmission of many traits from parents to children occurs, this property is not absolute. The nature of the genetic material is dual. Genes also have the ability to change and acquire new properties. Such gene changes are called mutations. And it is gene mutations that create the variability necessary for the evolution of living matter and the diversity of life forms. Mutations occur in any cells of the body, but only genes from germ cells can be transmitted to offspring.

The reasons for mutations are that many environmental factors with which each organism interacts throughout life can disrupt the strict orderliness of the process of self-reproduction of genes and chromosomes as a whole, leading to errors in inheritance. Experiments have established the following factors that cause mutations: ionizing radiation, chemicals and high temperature. Obviously, all these factors exist in the natural human environment (for example, natural background radiation, cosmic radiation). Mutations have always existed as a completely common natural phenomenon.

Being essentially errors in the transmission of genetic material, mutations are random and undirected in nature, that is, they can be both beneficial and harmful and relatively neutral for the body.

Beneficial mutations are fixed in the course of evolution and form the basis for the progressive development of life on Earth, while harmful ones, which reduce viability, are, as it were, the other side of the coin. They underlie hereditary diseases in all their diversity.

There are two types of mutations:

genetic (at the molecular level)
and chromosomal (changing the number or structure of chromosomes at the cellular level)

Both of them can be caused by the same factors.

How often do mutations occur?
Is the appearance of a sick child often associated with a new mutation?

If mutations occurred too often, then variability in living nature would prevail over heredity and no stable forms of life would exist. Logic obviously dictates that mutations are rare events, at least much rarer than the possibility of preserving the properties of genes when transmitted from parents to children.

The actual mutation rate for individual human genes averages from 1:105 to 1:108. This means that approximately one in a million germ cells carries a new mutation in each generation. Or, in other words, although this is a simplification, we can say that for every million cases of normal gene transmission, there is one case of mutation. The important fact is that, once it has arisen, this or that new mutation can then be transmitted to subsequent generations, that is, fixed by the mechanism of inheritance, since reverse mutations that return the gene to its original state are just as rare.

In populations, the ratio of the number of mutants and those who have inherited a harmful gene from their parents (segregants) among all patients depends both on the type of inheritance and on their ability to leave offspring. In classic recessive diseases, a harmful mutation can be transmitted unnoticed through many generations of healthy carriers until two carriers of the same harmful gene marry, and then almost every such case of the birth of a sick child is associated with inheritance, and not with a new mutation .

In dominant diseases, the proportion of mutants is inversely related to the fertility of patients. It is obvious that when a disease leads to early death or the inability of patients to have children, then inheriting the disease from parents is impossible. If the disease does not affect life expectancy or the ability to have children, then, on the contrary, inherited cases will predominate, and new mutations will be rare in comparison.

For example, in one of the forms of dwarfism (dominant achondroplasia), for social and biological reasons, the reproduction of dwarfs is significantly lower than average; in this population group there are approximately 5 times fewer children compared to others. If we take the average reproduction factor as normal as 1, then for dwarfs it will be equal to 0.2. This means that 80% of sufferers in each generation are the result of a new mutation, and only 20% of sufferers inherit dwarfism from their parents.

In hereditary diseases that are genetically linked to sex, the proportion of mutants among sick boys and men also depends on the relative fertility of the patients, but here cases of inheritance from mothers will always predominate, even in those diseases where patients do not leave offspring at all. The maximum proportion of new mutations in such lethal diseases does not exceed 1/3 of the cases, since men account for exactly one third of the X chromosomes of the entire population, and two thirds of them occur in women, who, as a rule, are healthy.

Can I have a child with the mutation if I received an increased dose of radiation?

The negative consequences of environmental pollution, both chemical and radioactive, are the problem of the century. Geneticists encounter it not as rarely as we would like in a wide range of issues: from occupational hazards to the deterioration of the environmental situation as a result of accidents at nuclear power plants. And the concern, for example, of people who survived the Chernobyl tragedy is understandable.

The genetic consequences of environmental pollution are indeed associated with an increase in the frequency of mutations, including harmful ones, leading to hereditary diseases. However, these consequences, fortunately, are not so catastrophic as to speak of the danger of genetic degeneration of humanity, at least at the present stage. In addition, if we consider the problem in relation to specific individuals and families, then we can say with confidence that the risk of having a sick child due to radiation or other harmful effects as a result of mutation is never high.

Although the frequency of mutations is increasing, it is not so much as to exceed a tenth or even a hundredth of a percent. In any case, for any person, even those exposed to obvious effects of mutagenic factors, the risk of negative consequences for offspring is much less than the genetic risk inherent in all people associated with the carriage of pathological genes inherited from ancestors.

In addition, not all mutations lead to immediate manifestation in the form of a disease. In many cases, even if a child receives a new mutation from one of the parents, he will be born completely healthy. After all, a significant part of mutations are recessive, that is, they do not manifest their harmful effects in carriers. And there are practically no cases where, with initially normal genes of both parents, a child receives the same new mutation from both father and mother. The probability of such an event is so negligible that the entire population of the Earth is not enough to realize it.

It also follows from this that the repeated occurrence of a mutation in the same family is almost impossible. Therefore, if healthy parents have a sick child with a dominant mutation, then their other children, that is, the patient’s brothers and sisters, should be healthy. However, for the offspring of a sick child, the risk of inheriting the disease will be 50% in accordance with classical rules.

Are there deviations from the usual rules of inheritance and what are they associated with?

Yes, there are. As an exception - sometimes only due to its rarity, such as the appearance of women with hemophilia. They occur more often, but in any case, deviations are caused by complex and numerous relationships between genes in the body and their interaction with the environment. In fact, exceptions reflect the same fundamental laws of genetics, but at a more complex level.

For example, many dominantly inherited diseases are characterized by strong variability in their severity, to the point that sometimes the symptoms of the disease in the carrier of the pathological gene may be completely absent. This phenomenon is called incomplete gene penetrance. Therefore, in the pedigrees of families with dominant diseases, so-called skipping generations are sometimes encountered, when known carriers of the gene, having both sick ancestors and sick descendants, are practically healthy.

In some cases, a more thorough examination of such carriers reveals, although minimal, erased, but quite definite manifestations. But it also happens that the methods at our disposal fail to detect any manifestations of a pathological gene, despite clear genetic evidence that a particular person has it.

The reasons for this phenomenon have not yet been sufficiently studied. It is believed that the harmful effect of a mutant gene can be modified and compensated by other genes or environmental factors, but the specific mechanisms of such modification and compensation in certain diseases are unclear.

It also happens that in some families, recessive diseases are passed on for several generations in a row so that they can be confused with dominant ones. If patients marry carriers of the gene for the same disease, then half of their children also inherit a “double dose” of the gene - a condition necessary for the disease to manifest itself. The same thing can happen in subsequent generations, although such “casuistry” occurs only in multiple consanguineous marriages.

Finally, the division of traits into dominant and recessive is not absolute. Sometimes this division is simply arbitrary. The same gene can be considered dominant in some cases, and recessive in others.

Using subtle research methods, it is often possible to recognize the effect of a recessive gene in a heterozygous state, even in completely healthy carriers. For example, the sickle cell hemoglobin gene in a heterozygous state causes the sickle-shaped red blood cells, which does not affect human health, but in a homozygous state it leads to a serious disease - sickle cell anemia.

What is the difference between gene and chromosomal mutations.
What are chromosomal diseases?

Chromosomes are carriers of genetic information at a more complex - cellular level of organization. Hereditary diseases can also be caused by chromosomal defects that arise during the formation of germ cells.

Each chromosome contains its own set of genes, located in a strict linear sequence, that is, certain genes are located not only in the same chromosomes in all people, but also in the same sections of these chromosomes.

Normal cells of the body contain a strictly defined number of paired chromosomes (hence the pairing of the genes they contain). In humans, in each cell, except the sex cells, there are 23 pairs (46) of chromosomes. Sex cells (eggs and sperm) contain 23 unpaired chromosomes - a single set of chromosomes and genes, since paired chromosomes separate during cell division. During fertilization, when the sperm and egg merge, a fetus - an embryo - develops from one cell (now with a complete double set of chromosomes and genes).

But the formation of germ cells sometimes occurs with chromosomal “errors”. These are mutations that lead to changes in the number or structure of chromosomes in a cell. This is why a fertilized egg may contain an excess or deficiency of chromosomal material compared to the norm. Obviously, such a chromosomal imbalance leads to gross disturbances in fetal development. This manifests itself in the form of spontaneous miscarriages and stillbirths, hereditary diseases, and syndromes called chromosomal.

The most famous example of a chromosomal disease is Down's disease (trisomy - the appearance of an extra 21st chromosome). Symptoms of this disease are easily identified by the appearance of the child. This includes a fold of skin in the inner corners of the eyes, which gives the face a Mongoloid appearance, a large tongue, short and thick fingers; upon careful examination, such children also have heart defects, vision and hearing defects, and mental retardation.

Fortunately, the likelihood of this disease and many other chromosomal abnormalities recurring in a family is low: in the vast majority of cases they are caused by random mutations. In addition, it is known that random chromosomal mutations occur more often at the end of the childbearing period.

Thus, as the age of mothers increases, the likelihood of a chromosomal error during egg maturation also increases, and therefore, such women have an increased risk of having a child with chromosomal abnormalities. If the overall incidence of Down syndrome among all newborn children is approximately 1:650, then for the offspring of young mothers (25 years and younger) it is significantly lower (less than 1:1000). The individual risk reaches an average level by the age of 30, it is higher by the age of 38 - 0.5% (1:200), and by the age of 39 - 1% (1:100), and at the age of over 40 it increases to 2- 3%.

Can people with chromosomal abnormalities be healthy?

Yes, they can with some types of chromosomal mutations, when it is not the number, but the structure of chromosomes that changes. The fact is that structural rearrangements at the initial moment of their appearance may turn out to be balanced - not accompanied by an excess or deficiency of chromosomal material.

For example, two unpaired chromosomes can exchange their sections carrying different genes if, during chromosome breaks, which are sometimes observed during cell division, their ends become sticky and stick together with free fragments of other chromosomes. As a result of such exchanges (translocations), the number of chromosomes in the cell is maintained, but this is how new chromosomes arise in which the principle of strict gene pairing is violated.

Another type of translocation is the gluing of two practically entire chromosomes with their “sticky” ends, as a result of which the total number of chromosomes is reduced by one, although no loss of chromosomal material occurs. A person who is a carrier of such a translocation is completely healthy, but the balanced structural rearrangements he has are no longer accidental, but quite naturally lead to chromosomal imbalance in his offspring, since a significant part of the germ cells of carriers of such translocations have excess or, conversely, insufficient chromosomal material.

Sometimes such carriers cannot have healthy children at all (however, such situations are extremely rare). For example, in carriers of a similar chromosomal anomaly - translocation between two identical chromosomes (say, fusion of the ends of the same 21st pair), 50% of eggs or sperm (depending on the sex of the carrier) contain 23 chromosomes, including a double one, and the remaining 50% contain one chromosome less than expected. During fertilization, cells with a double chromosome will receive another, 21st chromosome, and as a result, children with Down syndrome will be born. Cells with the missing 21st chromosome during fertilization give rise to a non-viable fetus, which spontaneously aborts in the first half of pregnancy.

Carriers of other types of translocations can also have healthy offspring. However, there is a risk of chromosomal imbalance, leading to severe developmental pathology in the offspring. This risk for the offspring of carriers of structural rearrangements is significantly higher than the risk of chromosomal abnormalities as a result of random new mutations.

In addition to translocations, there are other types of structural rearrangements of chromosomes that lead to similar negative consequences. Fortunately, inheritance of chromosomal abnormalities with a high risk of pathology is much less common in life than random chromosomal mutations. The ratio of cases of chromosomal diseases among their mutant and hereditary forms is approximately 95% and 5%, respectively.

How many hereditary diseases are already known?
Is their number increasing or decreasing in human history?

Based on general biological concepts, one would expect an approximate correspondence between the number of chromosomes in the body and the number of chromosomal diseases (and similarly between the number of genes and gene diseases). Indeed, several dozen chromosomal abnormalities with specific clinical symptoms are currently known (which actually exceeds the number of chromosomes, because different quantitative and structural changes in the same chromosome cause different diseases).

The number of known diseases caused by mutations of single genes (at the molecular level) is much larger and exceeds 2000. It is estimated that the number of genes on all human chromosomes is much greater. Many of them are not unique, since they are presented in the form of multiple repeating copies on different chromosomes. In addition, many mutations may not manifest themselves as diseases, but lead to embryonic death of the fetus. So the number of gene diseases approximately corresponds to the genetic structure of the organism.

With the development of medical genetic research throughout the world, the number of known hereditary diseases is gradually increasing, and many of them, which have become classic, have been known to people for a very long time. Now in the genetic literature there is a peculiar boom in publications about supposedly new cases and forms of hereditary diseases and syndromes, many of which are usually named after their discoverers.

Every few years, the famous American geneticist Victor McKusick publishes catalogs of hereditary traits and human diseases, compiled on the basis of computer analysis of world literature data. And each time, each subsequent edition differs from the previous one by an increasing number of such diseases. Obviously, this trend will continue, but it rather reflects an improvement in the recognition of hereditary diseases and more careful attention to them, rather than a real increase in their number in the process of evolution.

What is a gene mutation and how does mutation occur?
A gene mutation is a permanent change in the DNA sequence that makes up the entire set of genes called a genome, so that after mutation the gene sequence appears different from the genomes found in most people's cells. Mutations have a range of sizes; they can change from a single gene to mutation of a large part of a chromosome that contains hundreds of genes.

Gene mutations can be classified into two main areas:

Hereditary mutations are inherited from parents and are present throughout a person’s life in almost every cell of the body. These mutations are also called intrauterine mutation because they are present in the egg or sperm cells of the parents, which are also called germ cells. When an egg and sperm come together, the resulting fertilized egg receives DNA from both parents. If this DNA contains a mutation, the child that grows from the fertilized egg will have the mutation in every one of its cells.

Acquired (or somatic) mutations occur at some point during a person's life and are present only in some cells, such mutations do not occur in every cell in the body. These changes may be caused by environmental factors such as ultraviolet radiation from the sun or an error may occur when copying DNA during cell division. Acquired mutations in somatic cells (except sperm and eggs) cannot be passed on to the next generation.

De Novo (new) mutations can be either hereditary or somatic. In some cases, the mutation occurs in a person's egg or sperm but is not present in other human cells. In rare cases, a mutation occurs in a fertilized egg soon after the egg and sperm come together. (In such cases, it is often impossible to say exactly where the mutation occurred.) When the fertilized egg begins to divide, every cell of the growing embryo will have a mutation. The new mutations may explain genetic disorders in which the affected child has a mutation in every cell in the body, but the parents did not have such mutations and there is no history of mutations.

Somatic mutations, which occur in a single cell early in embryonic development can lead to a situation called mosaicism. These genetic changes are not present in the eggs or sperm of the parents, or in the fertilized egg, but appear a little later, when the embryo has already begun dividing and consists of several cells. Since all cells divide during growth and development, cells that arise from a cell with an altered gene will have mutations, while other cells will not have such mutations. Depending on the extent of the mutation and how many cells have undergone the mutation, mosaicism may cause health problems or not affect health at all.

Most disease-causing gene mutations rarely appear in the general population of a species. However, other genetic changes occur more frequently. Genetic changes that occur in more than 1 percent of the population are called polymorphisms. They are so common that they are now considered normal changes in DNA. Polymorphism is responsible for many common differences between people, such as eye color, hair color, and blood type.

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

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

Causes of mutations

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

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

The meaning of mutations

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

Classification of mutations by phenotype:
Mutation classifications:
according to Möller

Hypomorphic mutations.

The altered alleles act in the same direction as the wild-type alleles. Only less protein product is synthesized.a group of mutations according to the nature of their manifestation. They act in the same direction as the normal allele, but give a slightly weakened effect. For example, in Drosophila, the color of the eyes during mutation is much paler.
Amorphous mutations.

A mutation looks like a complete loss of a gene. For example, mutation white in Drosophila. (Greek “a” - negation, “morpha” - form) - a group of mutations according to the nature of their manifestation in the phenotype. Inactive against the typical effect of a normal allele. For example, the albinism gene completely inhibits the formation of pigment in animals or chlorophyll in plants.

Antimorphicmutations.

The mutant trait changes. For example, the color of corn kernels changes from purple to brown.(Greek “anti” - against, “morpha” - form) - a group of mutations according to the nature of their manifestation in the phenotype. They have an effect opposite to that of the normal allele. Thus, in corn, the original allele gives purple seed color, and the mutant allele causes the formation of brown pigment

Neomorphicmutations.

The mutant trait is new. It has no analogues in the wild type. (Greek “neos” - new, “morpha” - form) is a group of mutations that are atypical in the nature of their manifestation in the phenotype. Their action is completely different from the action of the original normal allele.

Hypermorphicmutations.

The amount of protein increases significantly. For example, the white eosine mutation means darker eyes.
by changing the DNA structure

(source: http://elmash.snu.edu.ua/material/iskust_intel/AI/11.htm , http://xn--90aeobapscbe.xn--p1ai/%D0%91%D0%B8%D0%BE%D0 %BB%D0%BE%D0%B3%D0%B8%D1%87%D0%B5%D1%81%D0%BA%D0%B8%D0%B9-%D1%81%D0%BB%D0% BE%D0%B2%D0%B0%D1%80%D1%8C/%D0%9D/596-%D0%9D%D0%B5%D0%BE%D0%BC%D0%BE%D1%80% D1%84%D0%BD%D1%8B%D0%B5-%D0%BC%D1%83%D1%82%D0%B0%D1%86%D0%B8%D0%B8)

By genotype:

Gene (point) mutations -these are changes in the number and/or sequence of nucleotides in the DNA structure (insertions, deletions, movements, substitutions of nucleotides) within individual genes, leading to a change in the quantity or quality of the corresponding protein products.

Base substitutions result in three types of mutant codons: with a changed meaning (missense mutations), with an unchanged meaning (neutral mutations) and meaningless or stop codons (nonsense mutations).

Mutations that change the sequence of nucleotides in a gene, i.e. the structure of the gene itself.

Gene duplications- doubling of a pair or several pairs of nucleotides (doubling of a G-C pair).

2. Gene insertions- insertion of a pair or several nar nucleotides (insertion of a G-C pair between A-T and T-A).

3. Gene deletions - loss of nucleotides (loss of the complementary T-A pair between A-T and G-C).

4. Gene inversions- rearrangement of a gene fragment (in the fragment, the original nucleotide sequence T-A, G-C is replaced by the reverse G-C, T-A).

5. Nucleotide substitutions- replacement of a pair of nucleotides with another; in this case, the total number of nucleotides does not change (replacement of T-A with C-G). One of the most common types of mutations. Duplications, insertions and deletions can lead to changes in the reading frame of the genetic code. Let's look at this with an example. Let's take the following initial sequence of nucleotides in DNA (for simplicity, we will consider only one of its chains): ATGACCTGCG... It will be read by the following triplets: ATG, ACC, GCG, A... Let's say a deletion has occurred, and at the very beginning of the sequence between A and G, nucleotide T has dropped out. As a result of this mutation, a changed nucleotide sequence will be obtained: AGACCTGCG, which will already be read by completely different triplets: AGA, CCG, CGA. Therefore, completely different amino acids will be combined into the polypeptide chain and, thus, a mutant protein will be synthesized, completely different from the normal one. In addition, as a result of gene mutations leading to a frameshift, stop codons TAA, TAG or TGA can be formed, stopping synthesis. The loss of an entire triplet leads to less severe genetic consequences than the loss of one or two nucleotides. Let's consider the same nucleotide sequence: ATGACCTGCG... Let's say a deletion occurred and a whole ACC triplet dropped out. The mutant gene will have an altered nucleotide sequence ATGGCGA, which will be read by the following triplets: ATG, HCG, A... It can be seen that after the loss of the triplet, the reading frame has not moved; the synthesized protein, although it will differ by one amino acid from the normal one, will generally be very similar to him. However, this difference in amino acid composition can lead to a change in the tertiary structure of the protein, which mainly determines its function, and the function of the mutant protein is likely to be reduced compared to the normal protein. This explains the fact that mutations are usually recessive.

Gene mutations manifest themselves phenotypically as a result of the synthesis of the corresponding proteins:

Gene mutations lead to changes in the structure of protein molecules and to the appearance of new characteristics and properties (for example, albinos in animals and plants, doubleness in flowers due to the transformation of stamens into petals and a decrease in their fertility, the formation of lethal and semi-lethal genes causing the death of the organism, etc. .d.). Gene mutations occur under the influence of mutagenic factors (biological, physical chemical) or spontaneously (accidentally). Gene mutations are also characteristic of genetic RNA viruses.

Genomic mutations - These are mutations that lead to the addition or loss of one, several or a complete haploid set of chromosomes ( rice. 118 , B). Different types of genomic mutations are called heteroploidy and polyploidy.

Genomic mutations characterized by changes in the number of chromosomes. In humans, polyploidy (including tetraploidy and triploidy) and aneuploidy are known.

Polyploidy - an increase in the number of sets of chromosomes, a multiple of the haploid one (Зn, 4n, 5n, etc.). Reasons: double fertilization and absence of the first meiotic division. In humans, polyploidy, as well as most aneuploidies, lead to the formation of lethal cells.

An exceptionally great role polyploidy in the origin of cultivated plants and their selection. All or most cultivated varieties of wheat, oats, rice, sugar cane, peanuts, beets, potatoes, plums, apples, pears, oranges, lemons, strawberries, and raspberries are polyploid. To this list should be added timothy, alfalfa, tobacco, cotton, roses, tulips, chrysanthemums, gladioli and many other human-cultivated crops. Autopolyploid plant mutants are usually larger than the original form. Tetraploids, as a rule, have a large vegetative mass. However, their fertility may sharply decrease due to non-disjunction of polyvalents in meiosis. Triploids are large and powerful plants, but completely or almost completely sterile, since the gametes they produce contain an incomplete set of chromosomes. Autopolynloid species are propagated vegetatively, since the fruits of such plants do not contain seeds.

Aneuploidy- change (decrease - monosomy, increase - trisomy) number chromosomes in the diploid set, i.e. not a multiple of haploid (2n+1, 2n-1, etc.). Mechanisms of occurrence: chromosome nondisjunction (chromosomes in anaphase move to one pole, while for each gamete with one extra chromosome there is another - without one chromosome) and “anaphase lag” (in anaphase, one of the moving chromosomes lags behind all the others).

*Trisomy - the presence of three homologous chromosomes in the karyotype (for example, on the 21st pair, which leads to the development of Down syndrome; on the 18th pair - Edwards syndrome; on the 13th pair - Patau syndrome).

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

*Tetrasomy and pentasomy:Tetrasomy (4 homologous chromosomes instead of a pair in a diploid set) and pentasomy (5 instead of 2) are extremely rare. Examples of tetrasomy and pentasomy in humans are karyotypes XXXX, XXYY, XXXY, XYYY, XXXXX, XXXXY, XXXYY, XYYYY and XXYYY. As a rule, with an increase in the number of “extra” chromosomes, the severity and severity of clinical symptoms increases.

Haploidy, - oppositepolyploidya phenomenon consisting of a multiple decrease in the number chromosomes in the offspring compared to the mother. Haploidy , as a rule, is the result of the development of an embryo from reduced (haploid) gametes or from cells functionally equivalent to them byapomixis, i.e. without fertilization. Haploidy rare in the animal world, but common in flowering plants: registered in more than 150 plant species from 70 genera of 33 families (including from the family of cereals, nightshades, orchids, legumes, etc.). Known in all major cultivated plants: wheat, rye, corn, rice, barley, sorghum, potatoes, tobacco, cotton, flax, beets, cabbage, pumpkin, cucumbers, tomatoes; in forage grasses: bluegrass, bromegrass, timothy, alfalfa, vetch, etc. Haploidy genetically determined and occurs in some species and varieties with a certain frequency (for example, in corn - 1 haploid per 1000 diploid plants). In the evolution of species Haploidy serves as a kind of mechanism that reduces the levelploidy . Haploidyused to solve a number of genetic problems: identifying the effect of gene dosage, obtaining aneuploids, studying the genetics of quantitative traits, genetic analysis, etc. In plant breedingHaploidyused to receive fromhaploids by doubling the number of chromosomes of homozygous lines, equivalent to self-pollinated lines in the production of hybrid seeds (for example, in corn), as well as for transferring the selection process from the polyploid to the diploid level (for example, in potatoes). Special shape Haploidy - androgenesis , in which the sperm nucleus replaces the egg nucleus, is used to produce male sterile analogues in corn.

Chromosomal mutations(aberrations) are characterized by changes in the structure of individual chromosomes. With them, the sequence of nucleotides in genes usually does not change, but a change in the number or position of genes due to aberrations can lead to a genetic imbalance, which has a detrimental effect on the normal development of the body.

Types of aberrationsand their mechanisms are presented in the figure.

There are intrachromosomal, interchromosomal and isochromosomal aberrations.

Chromosomal aberrations (chromosomal mutations, chromosomal rearrangements)- type of mutations that change the structure chromosomes . Classify deletions (loss of a chromosome section), inversions (changing the order of the genes of a chromosome region to reverse), duplications (repetition of a chromosome section), translocations (transfer of a chromosome section to another), as well as dicentric and ring chromosomes. Isochromosomes are also known to have two identical arms. If a rearrangement changes the structure of one chromosome, then such a rearrangement is called intrachromosomal (inversions, deletions, duplications, ring chromosomes), if two different ones, then interchromosomal (duplications, translocations, dicentric chromosomes). Chromosomal rearrangements are also divided into balanced and unbalanced. Balanced rearrangements (inversions, reciprocal translocations) do not lead to the loss or addition of genetic material during formation, therefore their carriers are, as a rule, phenotypically normal. Unbalanced rearrangements (deletions and duplications) change the dosage ratio of genes, and, as a rule, their carriage is associated with clinical deviations from the norm.

Intrachromosomal aberrations- aberrations within one chromosome. These include deletions, inversions and duplications.

*Deletion - loss of one of the chromosome sections (internal or terminal), which can cause disruption of embryogenesis and the formation of multiple developmental anomalies (for example, deletion in the region of the short arm of chromosome 5, designated as 5p-, leads to underdevelopment of the larynx, congenital heart defects, and mental retardation ). This symptom complex is designated as cat cry syndrome, since in sick children, due to an anomaly of the larynx, the crying resembles a cat's meow.

*Inversion - insertion of a chromosome fragment into its original place after a rotation of 180°. As a result, the order of genes is disrupted.

*Duplication- doubling (or multiplication) of any part of a chromosome (for example, trisomy on the short arm of chromosome 9 leads to the appearance of multiple congenital defects, including microcephaly, delayed physical, mental and intellectual development).

Interchromosomal aberrations- exchange of fragments between non-homologous chromosomes. They are called translocations. There are three types of translocations: reciprocal (exchange of fragments of two chromosomes), non-reciprocal (transfer of a fragment of one chromosome to another), Robertsonian (connection of two acrocentric chromosomes in the region of their centromeres with the loss of short arms, resulting in the formation of one metacentric chromosome instead of two acrocentric ones) .

* Reciprocal crosses - two crossing experiments characterized by directly opposite combinations gender and the characteristic being studied. In one experiment, a male with a certain dominant trait , crossed with a female having recessive trait . In the second, accordingly, a female with a dominant trait is crossed and a male with a recessive trait.
Reciprocal translocations are a balanced chromosomal rearrangement; during their formation, there is no loss of genetic material. They are one of the most common chromosomal abnormalities in the human population, with carrier frequencies ranging from 1/1300 to 1/700 . Carriers of reciprocal translocations, as a rule, are phenotypically normal, but have an increased likelihood of infertility, reduced fertility, spontaneous miscarriages and the birth of children with congenital hereditary diseases, since half of their gametes are genetically unbalanced due to the unbalanced divergence of rearranged chromosomes in meiosis.

Isochromosomal aberrations- formation of identical, but mirror fragments of two different chromosomes containing the same sets of genes. This occurs as a result of the transverse breaking of chromatids through the centromeres (hence the other name - centric connection).

(aberrations, rearrangements) - changes in the position of chromosome sections; lead to changes in the size and shape of chromosomes. These changes can involve both sections of one chromosome and sections of different, non-homologous chromosomes, therefore chromosomal mutations (rearrangements) are divided into intra- and interchromosomal.

A. Intrachromosomal mutations

1. Chromosomal duplications - doubling of a chromosome section.

2. Chromosomal deletions - loss of a chromosome region.

Chromosomal inversions are a chromosome break, turning the detached section 180° and inserting it into its original place. B. Interchromosomal mutations

1. Translocation - exchange of sections between non-homologous chromosomes (in meiosis). type chromosomal mutations , in which a portion of a chromosome is transferred to a non-homologous chromosome . Separately allocate reciprocal translocations, in which there is a mutual exchange of sections between non-homologous chromosomes, andRobertson'stranslocations, or centric fusions, in which acrocentric chromosomes merge with complete or partial loss of material from the short arms.Translocations, just like others, leukemia.

2. Transposition - inclusion of a chromosome section into another, non-homologous chromosome without mutual exchange.

Score for work: 5

Encyclopedic YouTube

1 / 5

✪ 5 HORRIBLE human mutations that SHOCKED scientists

✪ Types of mutations. Gene mutations

✪ 10 CRAZY HUMAN MUTATIONS

✪ Types of mutations. Genomic and chromosomal mutations

✪ Biology lesson No. 53. Mutations. Types of mutations.

Subtitles

Nick Vujicic was born with a rare hereditary disease called Tetra-Amelia syndrome. The boy was missing full arms and legs, but had one partial foot with two fused toes; this allowed the boy, after surgical separation of his fingers, to learn to walk, swim, skateboard, work on a computer and write. After experiencing disability as a child, he learned to live with his disability, sharing his experiences with others and becoming a world-renowned motivational speaker. In 2012, Nick Vujicic got married. And subsequently the couple had 2 absolutely healthy sons. In 2015, a baby was born in Egypt with one eye in the middle of his forehead. Doctors said the newborn boy suffered from cyclopia, an unusual condition whose name comes from the one-eyed giants of Greek mythology. The disease was a consequence of radiation exposure in the womb. Cyclopia is one of the rarest forms of birth defects. Babies born with this condition often die soon after birth because they often have other serious defects, including damage to the heart and other organs. In the USA, in the state of Iowa, Isaac Brown lives, who has been diagnosed with a very unusual disease. The essence of this disease is that the child does not feel pain. Because of this, Isaac's parents are forced to constantly monitor their son to prevent serious injury to the child. The boy's ability not to feel pain is the result of a rare genetic disease. Of course, when a boy is injured, he experiences pain, only these sensations are several times weaker than in other people. After breaking his leg, Isaac realized that there was simply something wrong with his leg, since he could not walk as usual, but there was no pain. In addition to the fact that the baby does not feel pain, during the examination he was found to have anhidrosis, that is, there is no ability to regulate his own body temperature. Experts are currently studying samples of the boy's DNA in the hope of finding a defect in the genes and developing methods for treating such a disease. A little American girl named Gabby Williams has a rare condition. She will remain forever young. Now she is 11 years old and weighs 5 kilograms. At the same time, she has the face and body of a child. Her strange deviation was dubbed the real story of Benjamin Button, because the girl ages by a year in four years. And this is an amazing phenomenon, over which dozens of specialists are racking their brains. When she was born, she was purple and blind. Tests showed she had a brain abnormality and her optic nerve was damaged. She has two heart defects, a cleft palate, and an abnormal swallowing reflex, so she can only eat through a tube in her nose. The girl is also completely mute. The baby can only cry or sometimes smile. There are no deviations in DNA, but Gabby hardly ages in comparison with other people, and no one knows what the reason is. Javier Botet suffers from a rare genetic disorder known as Marfan Syndrome. People with this disease are tall, thin, and have elongated limbs and fingers. Their bones are not only elongated, but also have amazing flexibility. It is worth noting that without treatment and care, those suffering from Marfan Syndrome rarely live beyond the age of forty. Javier Botet is 2 meters tall and weighs only 45 kg. These specific external data, features of the physical structure and genetic system helped Botet become “one of the people” in horror films. He played the terrifyingly thin zombie in the Report trilogy, as well as creepy ghosts in Mom, Crimson Peak and The Conjuring 2.

Causes of mutations

Mutations are divided into spontaneous And induced. Spontaneous mutations occur spontaneously throughout the life of an organism under normal environmental conditions with a frequency of about 10 − 9 (\displaystyle 10^(-9)) - 10 − 12 (\displaystyle 10^(-12)) per nucleotide for the cellular generation of an organism.

Induced mutations are heritable changes in the genome that arise as a result of certain mutagenic effects in artificial (experimental) conditions or under adverse environmental influences.

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

Relationship between mutations and DNA replication

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

Relationship between mutations and DNA recombination

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

Relationship between mutations and DNA repair

Tautomeric model of mutagenesis

It is assumed that one of the reasons for the formation of base substitution mutations is deamination of 5-methylcytosine, which can cause transitions from cytosine to thymine. Due to the deamination of the cytosine opposite it, uracil can be included in the DNA chain (a U-G pair is formed instead of the canonical C-G pair). During DNA replication opposite uracil, adenine is included in the new chain, a U-A pair is formed, and during the next replication it is replaced by a T-A pair, that is, a transition occurs (a point replacement of a pyrimidine with another pyrimidine or a purine with another purine).

Mutation classifications

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

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

genomic;
chromosomal;
genetic.

A point mutation, or single base substitution, is a type of mutation in DNA or RNA that is characterized by the replacement of one nitrogenous base with another. The term also applies to pairwise nucleotide substitutions. The term point mutation also includes insertions and deletions of one or more nucleotides. There are several types of point mutations.

Complex mutations also occur. These are changes in DNA when one section of it is replaced by a section of a different length and a different nucleotide composition.

Point mutations can appear opposite damage to the DNA molecule that can stop DNA synthesis. For example, opposite cyclobutane pyrimidine dimers. Such mutations are called target mutations (from the word “target”). Cyclobutane pyrimidine dimers cause both targeted base substitution mutations and targeted frameshift mutations.

Sometimes point mutations occur in so-called undamaged regions of DNA, often in a small vicinity of photodimers. Such mutations are called untargeted base substitution mutations or untargeted frameshift mutations.

Point mutations do not always form immediately after exposure to a mutagen. Sometimes they appear after dozens of replication cycles. This phenomenon is called delayed mutations. With genomic instability, the main cause of the formation of malignant tumors, the number of untargeted and delayed mutations increases sharply.

There are four possible genetic consequences of point mutations: 1) preservation of the meaning of the codon due to the degeneracy of the genetic code (synonymous nucleotide substitution), 2) change in the meaning of the codon, leading to the replacement of an amino acid in the corresponding place of the polypeptide chain (missense mutation), 3) formation of a meaningless codon with premature termination (nonsense mutation). There are three meaningless codons in the genetic code: amber - UAG, ocher - UAA and opal - UGA (in accordance with this, mutations leading to the formation of meaningless triplets are also named - for example, amber mutation), 4) reverse substitution (stop codon to sense codon).

By influence on gene expression mutations are divided into two categories: mutations such as base pair substitutions And reading frame shift type. The latter are deletions or insertions of nucleotides, the number of which is not a multiple of three, which is associated with the triplet nature of the genetic code.

The primary mutation is sometimes called direct mutation, and a mutation that restores the original structure of the gene is reverse mutation, or reversion. A return to the original phenotype in a mutant organism due to restoration of the function of the mutant gene often occurs not due to true reversion, but due to a mutation in another part of the same gene or even another non-allelic gene. In this case, the recurrent mutation is called a suppressor mutation. The genetic mechanisms due to which the mutant phenotype is suppressed are very diverse.

Kidney mutations(sports) - persistent somatic mutations occurring in the cells of plant growth points. Lead to clonal variability. They are preserved during vegetative propagation. Many varieties of cultivated plants are bud mutations.

Consequences of mutations for cells and organisms

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

In addition, the frequency of mutations of different genes and different regions within one gene naturally varies. It is also known that higher organisms use “targeted” (that is, occurring in certain sections of DNA) mutations in their mechanisms