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MUTATION (Latin mutatio change, change) — the general property of live organisms which is the cornerstone of evolution and selections of all life forms and consisting in suddenly arising change of genetic information. Studying of the nature of M. is extremely important for medicine from the point of view of prevention and treatment hereditary diseases (see).

Sudden emergence of hereditary changes was described in 18 — 19 centuries. This phenomenon was known also to Ch. Darwin. However studying of the phenomenon of M. began only after a sformirovaniye of experimental genetics as sciences since the beginning of 20 century. The term «mutation» in modern understanding began to be used in scientific literature since 1901 after issue of the book X. de of Fris «The mutational theory». Earlier the individuals deviating on the signs normal individuals called the word «mutation».

After establishment of that fact that genetic information is written down in molecules nucleinic to - t in M.'s theory there was a fundamental change (see. Gene , Deoxyribonucleic acid ). It was established later that the inherited changes can happen not only in DNA of chromosomes, but also in DNA of cytoplasmatic self-replicating structures. In this case speak about cytoplasmatic M.

Process of emergence of M. under natural conditions or as a result of experimental influence various physical., chemical and biol, factors is called mutagenesis (see).

The individual bearing M., action a cut it is shown in a phenotype, call a mutant. M can change external signs of an individual, her physical features, biochemical, processes, to break developments, to weaken viability (sublethal M.) or even to lead to death of an individual (lethal M.) etc. Along with M., influence to-rykh on development of an individual is expressed clearly, there are M. which are poorly changing normal development of an individual. Such M. received the name of small. M can arise in germinal and in somatic cells, in cells of culture of fabric and, at last, in the molecules DNA allocated from cells.

On M.'s action can be harmful, neutral and useful, however, their such assessment is relative as M.'s effect depends on conditions of the environment. E.g., are harmful to the butterflies living on birches, M. of a melanizm because dark butterflies on light trunks of birches are easier found by birds. However in industrial districts where trunks of trees are more dark, M. of a melanizm became useful.

Considering value M. for succeeding generations, they are divided on generative and somatic. Generative M. arise in formative cells and pass into succeeding generations. Somatic M. are not transferred to posterity. Appearing in a single cell of a body, they are inherited only by descendants of this cell, forming mutant fabric in an organism. It is natural that in case of vegetative reproduction somatic M. can remain it is long. Somatic M. are widely known also for animal organisms. At a drosophila at early stages of development of an eye a normal allele (see. Alleles ), the eye defining red coloring, in a separate cell can mutate in the allele defining white coloring of eyes. The cell containing again appeared allele gives rise to the fabric occupying a part of an eye therefore against the background of red coloring in an eye of such drosophila the sector of white color (appears see. Mosaicism ). The somatic M. arising at this or that stage of ontogenesis genetically allocates a stem cell and the fabric which came from it that in nek-ry cases allows to study patterns of an ontogeny. Somatic M. can exert serious impact on life of an individual. The human body consists approximately from 10 14 cells. If to assume that the nek-ry certain gene mutates with such low frequency as 10 - 8 , and in this case the human body shall contain more than 10 6 the cells bearing M. only in this gene. The number of genes at the person is conditionally equal to 10 5 . Even if to assume that the frequency of a mutirovaniye extremely low (10 - 8 ), the huge number of mutant cells all the same turns out (10 11 ). It shows that very big population of cells of a body of the person is influenced by M. Mutabelnost, i.e. ability to change, is sharply raised in cells of cancer tumors. Apparently, in some cases emergence of cancer has a talk somatic M. with the subsequent fabric selection.

Successful development of researches on cultivation of tissues of the person allowed to determine in direct experiences M.'s frequency of genes in cells, and also to investigate the genetic nature of malignant growth in an experiment.

The signs inherent in this look are developed in the course of evolution and controlled by normal alleles, to-rye usually dominantna in relation to other gene of allelic couple. It is obvious that the mutational process going in normal individuals generally turns dominant normal alleles into mutant recessive. However process of a mutirovaniye is reversible. The subsequent M. in a mutant gene lead to emergence not only a series of other recessive alleles, but also to emergence of normal dominant alleles. Changes of normal alleles in mutant call direct mutations (And -> and), transformations of mutant recessive alleles in normal dominant — reverse mutations (and -> And).

Under natural conditions M. appear under the influence of factors of external and internal environment and are designated by the term «natural (or spontaneous) mutations». The m received in experimental conditions call induced. The agents causing M. received the name mutagens (see). In the course of a natural mutirovaniye genes are mutated with a certain frequency. Average frequency of M. on one gene in one generation at bacteria — 10 - 7 , at a drosophila in formative cells — 10 - 5 etc.

In the same organism different genes are mutated with a different frequency. From eight genes of an endosperm of corn the gene controlling coloring mutates with a frequency of 496*10 - 6 , the gene of Wx controlling starchiness of an endosperm mutates 330 times less often, with a frequency equal only 1,5*10 - 6 . Frequency of a mutirovaniye of other six genes represents average size between the given extreme values.

Determination of frequency of M. at the person is much more difficult, than at bacteria or plants. However in nek-ry cases it is approximately established. So, intestinal the polypose mutates a gene with a frequency of 10 - 4 , and a gene of the progressing muscular dystrophy — with a frequency of 10 - 5 . Frequency of a mutirovaniye at direct M. (And —> and) is, as a rule, higher, than the frequency of a mutirovaniye at the return M. (and —> And); direct and return M.' ratio is characteristic of each separate gene. If to consider direct and return M.' frequency totally on many genes, then it becomes clear that process of a mutirovaniye is mass, statistically well fixed process.

In 1921 S. Wright suggested to call stability of mass process of a mutirovaniye the term «pressure of mutations», to-ry characterizes natural life of populations of organisms (see. Population genetics ). Direct and return M. not necessarily are jump from one state only to another. Recessive and dominant alleles change is diverse, as a result from same locus (see) in different organisms there is a set of alleles. Studying of populations showed that in nek-ry cases the quantity of alleles for separate genes is estimated in tens and even hundreds. The gene of W localized in X-chromosome at a drosophila and defining color of eyes has more than ten alleles, to-rye control eosin, honey, apricot, cherry, coral and white color of eyes of fruit flies. A gene With + , causing emergence of gray coloring of wool in a rabbit (aguta), mutates in three different recessive alleles: allele of C ch provides chinchilla coloring of a rabbit, an allele With h — white with black spots (the Himalaya rabbit), an allele with — purely white.

Practically any gene, testing M., gives a series of multiple alleles. Alleles of genes are a classical example of a series of alleles blood groups (see) at the person.

Antigen A. in erythrocytes antigen B — appears in the presence at people of a gene of IA, at action of a gene of IB. Both of these genes are allelic, their influence is independent from each other, they are not connected by dominance or recession. Such independent manifestation of alleles when heterozygous individuals have two signs under the influence of two alleles, received the name to dominance.

Multiple alleles participate in creation natural adaptive biol, features of organisms.

When M. occurs in a separate gene, speak about gene, or tochko-vy M. At structural changes of chromosomes (structural M., aberrations of chromosomes) or their numbers, it is about chromosome mutations. The essence of aberrations of chromosomes consists in dislocation of sites of chromosomes, i.e. their movement in this chromosome or between different chromosomes. During an initial stage of development of genetics structural M.' presence of chromosomes was established by way genetic analysis (see) and primitive overseeing by chromosomes. The possibility of thin observation of chromosome mutations under a microscope appeared after opening of giant chromosomes in sialadens of a drosophila. In 1930 D. Kostov assumed, and Peynter (T. S. Painter) in 1933 proved that the structure of these chromosomes seen under a microscope presented by a number of consistently located disks reflects their genetic contents. Structural M. are widely presented in populations of plants, animals and the person, on their basis evolution of specific is carried out karyotypes (see). The main types of structural M. of chromosomes are deletions (see), symmetric and asymmetric translocations (see), formation of closed chromosomes (centric and atsentrichesky), duplications (see), inversions (see).

Translocations represent exchange of fragments between different chromosomes. It becomes possible at coincidence of two gaps — one in one chromosome and another — in another. The arising four fragments freely are combined with each other.

Divisions, i.e. loss of the site of a chromosome, can result from one rupture of a chromosome. The trailer fragment deprived centromeres is lost. Such type of deletions received the name of trailer. At emergence of two gaps the average site of a chromosome drops out, and trailer fragments connect in one chromosome. So there are intersticial deletions. The size of deletions can be various. When noticeable blocks of genes are lost, zygotes perish. Rather small deletions are transmitted on generations through heterozygous individuals. However at emergence of zygotes, homozygous on the lost site, they, as a rule, perish. The m caused by deletion in this case have lethal effect.

A number of the deletions serving as the reason of hereditary diseases is found in the person. So, trailer shortage of a part of a short shoulder of the 5th chromosome causes emergence of a so-called syndrome of shout of a cat, intersticial deletion in the 21st chromosome is the reason of malignant anemia.

The phenomena of duplication, i.e. doubling of any block of genes in chromosomes, can be a source of increase in volume of genetic information of types, they are important from the evolutionary point of view.

The term «inversion» was entered by A. H. Sturtevant in 1926 during the studying of a crossing-over at females of a drosophila; it showed that the median site of one of chromosomes of the 3rd couple is turned on 180 °. Inversions can be single and difficult, the last lead to noticeable shift of blocks of genes. If at formation of inversion both gaps pass one party from centromeres, paracentric inversion is formed. Such inversion does not change morphology of chromosomes. However heterozygous individuals on the inverted site for the concluded block of genes in it have no crossing-over (see. Recombination ). It provides inheritance of this block entirely. If inversion takes to a centromere, then there is pericentric inversion. When two inversions directly adjoin to each other, so-called tandem inversions appear. This type of inversions has two forms: direct tandem inversion (at preservation by both inversions of genes initially inherent to their blocks in a chromosome) and the return tandem inversion when the blocks of genes concluded in inversions are interchanged the position. In the presence of one inversion the second can happen on its internal site. This type of chromosomal M. is called the included inversion. If the second inversion happens to partial capture of a part of material of the first inversion and a part of genes from the neighboring normal region of a chromosome, then it call coming. biol, effects of a crossing-over are the reason of absence on the site of inversion at heterozygous individuals of exchange of genes. At the heterozygous individual having a normal chromosome — 12345678 and a chromosome with inversion — 12654378, the crossing-over on site 5 — 6 will lead to emergence of two krossingoverny chromosomes — 126678 and 123455437 8. In half of such chromosomes a part of genes is lost, and in other half a part of genes is presented at the double. Such effects of a crossing-over observe at paracentric and pericentric inversions. In the latter case, besides, the chromatid with two centromeres (dicentrics) and a fragment without centromeres appears. Emergence of an unbalanced chromosome in a zygote leads of it to death. The phenomenon when at individuals a part of zygotes regularly perishes, and other part is normal, received the name of semisterility.

The phenomenon of a translocation which is the cornerstone of one more type of chromosomal M. consists in transfer of the site of a chromosome on other chromosome or to other place of the same chromosome. In most cases at translocations of a chromosome exchange sites. These translocations called mutual, unlike non-mutual translocations when the average site of one chromosome is inserted into other chromosome. In this case two gaps are necessary for formation of a median fragment in one chromosome. The chromosome, in to-ruyu is inserted the foreign median site, broken off in one place. Mutual translocations happen two types: 1) symmetric, arising at such exchange of sites when in each chromosome about one centromere remains (similar translocations are connected with preservation of all genetic material, to-ry it is differently distributed between chromosomes, they are given to succeeding generations); 2) asymmetric, observed at merge of two centromere fragments and formation of a dicentric chromosome. Connection of two atsentrichesky fragments leads to emergence of one atsentrichesky fragment. In time replications (see) chromosomes in a phase of synthesis of DNA the dicentric chromosome and an atsentrichesky fragment double. In the first mitosis atsentrichesky fragments are lost. As for a dicentric, it or forms a chromosome bridge and is torn, or, at an otkhozhdeniya both centromere to one pole, gets to a daughter cell. Through a number of mitoses the dicentric is lost. Symmetric translocations thanks to action of forces of an attraction of homologous loci in a pro-phase meiosis (see) form a crosswise configuration. At discrepancy often form the ring consisting of four chromosomes of such figure of a chromosome. As symmetric translocations accompany only redistribution of gene material, an individual, heterozygous on translocations, along with normal give gametes with disturbances in the form of big duplications or deletions. The zygotes arising with the participation of such gametes perish that results in semisterility of plants and animal, heterozygous on a mutual translocation. Translocations not only change an order of genes, but also chromosome number in connection with acquisition or loss a centromere.

As a peculiar type of structural M. serves emergence of closed chromosomes. Normal in a karyotype closed chromosomes do not occur at animals and plants. Formation of a closed chromosome is connected with emergence in one chromosome of two gaps therefore are formed two trailer and one median fragment. The median site connects places of gaps and becomes isolated in a ring. If the median site of a chromosome included to a centromere, then there is a centric ring. Such closed chromosome is transferred to generations of cells and organisms. If the closed chromosome is formed of the median site of a chromosome deprived centromeres there is an atsentrichesky closed chromosome.

There are two types M. of chromosome number: an aneuploidy, i.e. loss or emergence of ctetosomes (M.'s unit one or several chromosomes, number to-rykh less, than haploid set serve); the gaploidiya and a polyploidy, multiple change of chromosome number, at them M.'s unit serves a haploid set of chromosomes (n). Gaploidiya — loss of the whole set (2n — n). The polyploidy arises at addition of the whole sets (2n + n, 2n + 2n etc.). The individuals bearing three sets of chromosomes are called triploids (Zn), four sets — tetraploids (4n) etc. of Aneutsloidiya arise in the course of a mitosis or meiosis, as a rule, owing to not discrepancy of homologous chromosomes. The following types of an aneuploidy are characteristic of diploids: a nulisomiya — loss of couple of homologous chromosomes (2n — 2r where r designates a homolog); a monosomy — loss of one chromosome from any couple (2n — 1); a trisomy — emergence of one excess chromosome (2n + 1); a tetrasomiya — existence of two excess homologous chromosomes (2n + 2r). At more difficult phenomena the double monosomy (2n — 1 — 1), a double trisomy (2n + 1 + 1), a combination of two types (2n — 1, 2n + 1) etc. is possible. Aneuploidies cause disturbance of a genic balance and, as a rule, considerably change signs of an individual. Tetrasomiya allows to localize genes in certain chromosomes since existence of four chromosomes creates system from three alleles at one of parents that changes the nature of splitting.

Aneuploidies at the person explain emergence of a number of hereditary diseases. For the first time the aneuploidy in the person was found Ge. Le Jeune, etc. in 1959 in the analysis of chromosomes of the patient with a Down syndrome (see. Down disease ). It turned out that patients have the trisomy on the 21st chromosome which is regularly arising with a frequency of 1 on 700 births. With a frequency of 1 on 5000 ova owing to not discrepancy of X-chromosomes there is an ovum deprived of a gonosome (see. Floor ). Women with a genotype of HO bear signs of a syndrome of Shereshevsky — Turner (see. Turner syndrome ). As a result of not discrepancy of X-chromosomes there are people with 47 chromosomes including the XXY set. Children of XXY are boys with a so-called syndrome of Klaynfelter (see. Klaynfeltera syndrome ). Also other aneuploid changes are found in the person, in particular a trisomy and a tetrasomiya on X-chromosome and the combined trisomy. Difficult disturbances, numbers of gonosomes are found in men (XXXY, XXYY, XXXXY, XYY) and women (XXXX, ХХХХХ). The aneuploidy often arises as somatic M. In case of somatic M. the aneuploidy as a result of not discrepancy of homologs in a mitosis is shown as a chromosomal mosaic, at a cut one fabrics have a normal set of chromosomes, and others — consist of cells with aneuploid chromosome number. Chromosomal mosaics on gonosomes are found in the person: XO/XX, XO/XY, XX/XY, XXY/XX hkh/hkhkh, hkhkh/ho, hkhkhkh/hkhkhkhkh, etc. (see. Chromosomal diseases ).

The term «gaploidiya» or «mono-ploidiya» designate existence in a genome only of one homolog from each couple of chromosomes. At the higher plants and animals diploidy of chromosomes (paired relationship of alleles) comprises one of advantages of a syngenesis, viability of an organism at an ontogeny, i.e. is the major genetic phenomenon.

The polyploidy is widely presented at plants. Polyploid plants differ from diploid in many morfol., fiziol, and biochemical, features. Their cells and kernels have the big sizes, than at diploids. The general sizes of plants, their flowers, seeds and fruits are increased.

The polyploidy among animals is widespread less, than among plants. It is connected with the fact that the genic balance between gonosomes and autosomes is of great importance for animals. The deviation from diploidy often causes sterility in animals. Polyploid types are found among worms, insects, Crustacea, fishes, amphibians, reptiles and other animals. Among these forms nek-ry types lost ability to a syngenesis. Connection of a parthenogenesis with on-liploidnostyyu is established at crustaceans of the sort Artemia, wood lice of Trichoni-seus, butterflies of Solenobia, etc. The tetraploid forms breeding sexually are separate species of fish, the South American frog of Odontophymis ame-ricanus and nek-ry other organisms. The Pacific salmons are polyploids, the same concerns a number of species of cyprinid fishes.

The reason gene, or so-called dot, M. is replacement of one nitrogen base in molecule DNA on another, loss, an insert or shift of nitrogen bases in molecule DNA. As a result of gene M. at the person can develop patol, states, a pathogeny to-rykh it is various. Loss of one or several nucleotides (deletion) can lead to desequencing of the amino-acid remains in a polypeptide chain of the coded protein, i.e. to disturbance of its primary structure. Deletion of several nucleotides can lead to complete cessation of synthesis of the protein coded by a mutant gene. The similar effect is possible in case of transformation of the triplet coding inclusion in a polipep-tidny chain of a certain amino acid, in the triplet coding the end of synthesis of a polypeptide chain.

Gene M., without changing amount of synthesizable protein, can change its conformation and by that — its enzymatic activity up to its total disappearance, and, on the contrary, without influencing enzymatic activity of protein — to change the speed of its synthesis, synthesis of its inhibitor or the activator. All this finally leads to development enzymopathies (see).

All genetic variety of people anyway is a consequence of M. Average frequency of emergence of M. on one gamete of the person was close to 1*10 - 5 . M.'s frequency of a normal allele in an allele hemophilias (see) or in an allele albinism (see) makes 3*10 - 5 . Cells of marrow of the person in culture of fabric are mutated from a normal allele in an allele of stability to 8 azaguanine with a frequency of 7*10 - 4 .

Huge polymorphism in human populations exists not only at the expense of separate genes, but also at the expense of their combinations creating polymorphic systems of enzymes, blood groups, variability on alleles of a tissue incompatibility in a locus of HLA, etc.

Bibliography: Auerbach Sch. Problems of a mutagenesis, the lane with English, M., 1978; B are and sh N of e in Yu. I. and Velti-shch of e in Yu. E. Hereditary diseases of a metabolism at children, JI., 1978; Berdyshev G. D. and Krivoruchko I. F. Genetics of the person with fundamentals of medical genetics, Kiev, 1979; B about the p-kov H. P. Genetika of the person, M., 1978; Dubinin N. P. The general, genetics, M., 1976; M and to yu with and to V. A. Ancestral features of the person, the lane with English, M., 1976; McKusick Y. Mendelian inheritance in man, Baltimore, 1978.

H. P. Dubinin.