RECOMBINATION (Latin re-the prefix meaning repetition, resuming, + late lat. combinatio connection) — process of a regrouping of genetic material, to-rogo is result emergence of new combinations of genetic structures (genes, chromosomes, sites of chromosomes etc.) and the signs controlled by them at affiliated individuals or cells. This or that type of genetic R. exists at all live organisms and makes a material basis of hereditary variability (see). The river at eukaryotes is carried out in mitosis (see) and in meiosis (see) when there is a distribution of chromosomes and a crossing-over.
The following is an example of genetic R.: e.g., if one of parents has a fair hair and brown eyes, and another — dark hair and blue eyes, then their children can inherit a combination of hair color and eyes any of parents or these signs will be shown at them in new, recombinant combinations (a fair hair and blue eyes or dark hair and brown eyes).
There are several types of genetic R. U of eukaryotes main types of R. are: River of not linked genes as a result of independent distribution of nonhomologous couples of chromosomes (see. Chromosomes ) in meiosis and an accidental meeting of gametes at fertilization (see. Mendel laws ); The river of linked genes and homologous chromosomes carrying them as a result of a crossing-over. Sometimes this two types of R. designate as R. of chromosomes in a broad sense though more often only process of a crossing-over and its result understand iod P. of chromosomes. At prokariot (bacteria, viruses) an analog of a crossing-over is the recombination of DNA. About a range of the variability provided to R. it is possible to judge by the following example. In normal chromosomal complement of the person 23 couples of chromosomes (see. Chromosomal complement ). If at the individual on each couple of chromosomes heterozygosity at least in one locus takes place (actually degree of heterozygosity at the person much higher), then only due to independent distribution of nonhomologous couples of chromosomes in meiosis such individual will give 2 23 , i.e. apprx. 10 million, genetic options of gametes. Existence of a crossing-over at least will double this number. As the same can take place at the marriage partner moreover and with R.'s involvement on other genes, a potential genetic variety of descendants of one human couple will be about several billion options. Sets this example also that the range of combinative variability is especially wide at a syngenesis multichromosomal biol. types, including and the person that practically provides genetic uniqueness of each individual.
At metaphytes, in addition to meiotic R., can take place and mitotic (somatic) R., as a result a cut at individuals, heterozygous on any signs, emergence of sites (spots) of fabric formed by clones of cells of a recombinant genotype is possible, and individuals become so-called mosaics (see. Mosaicism ). The earlier in ontogenesis there will be somatic R., the big share of cells of a body will have recombinant type. In the first division of crushing of R. the mosaic with equal quantities of stem and recombinant cells can give. If mitotic R. mentions not only somatic cells, but also initial cells of gonads, speak about gonadal and somatic mosaicism. In this case a part of posterity can inherit a recombinant combination of genes. Spontaneous level of mitotic R. is usually very low, but can strongly increase as a result of ionizing radiation and others mutagens (see).
The recombination of chromosomes
of homologous chromosomes in meiosis is proved to R. by T. Morgan with sotr. during the studying of cases of deficit of recombinants in di - and trigibridny crossings in relation to number of the expected recombinants according to the law of an independent combination. The following quantitative consistent patterns were determined.
1. R.'s frequency of each this couple it is linked the inherited genes it is constant and does not depend on their initial combination. E.g., at a genotype of a dihybrid of AB/ab the frequency of recombinant gametes of A and av will be same as frequency of recombinant gametes of AV and ab.
2. R.'s frequency of different couples it is linked the inherited genes it is various and can make from small shares of percent almost up to 50% (the last corresponds to the expected frequency of recombinants at not linked, independent inheritance).
3. With a small and medium frequency of R. (no more than 20%) at trigibrid on stseplenno-nasleduye-mym to signs the greatest value of frequency of R. is equal to the sum of two others. E.g., at a trigibrid AVS/as if R.'s frequency between And yes In makes 5%, and between In and With — 10%, R.'s frequency between And yes With will appear equal 15%.
These patterns best of all are explained by the fact that stsegshenno-heritage is defined by the genes located in the linear sequence in the fixed loci of the same couple of homologous chromosomes, and their R. is result of exchange of sites between homologs (fig. 1), and, than further from each other there are two genes, that a high probability of their River. Such exchange of sites of two homologous chromosomes in meiosis received the name of a crossing-over or decussation of chromosomes, and its products — krossoverny chromosomes. Complex genetic (on phenotypical signs) and cytologic (on marker chromosomes) R.'s studying allowed to prove reality of existence and generality of process of a crossing-over in meiosis at all eukaryotic organisms. Normal the crossing-over occurs in strictly homologous points of couple of chromosomes so that they exchange segments, strictly identical on the gene sequences. The fact that at the same time do not observe loss of the studied markers allowed to draw a conclusion that the crossing-over occurs between genes without disturbance of their integrity. Relative constancy of frequency of a crossing-over on each this site of a chromosome formed the basis for election of this frequency as a measure of distance between genes.
Its piece is accepted to unit of genetic length of a chromosome, on Krom the frequency of a meiotic crossing-over is equal to 1%. This unit is called morganidy, krossoverny unit or unit of the card. The last name is connected with the fact that complete data according to R. of the stseplenno-inherited genes allow to construct the linear genetic maps of chromosomes describing the sequence of genes and genetic distances between them (see. Chromosome map ). In process of accumulation of data on genetic distances between markers always it turned out that the number of the revealed linkage groups has the upper limit chromosome number in a haploid set of this look. It is one more argument in favor of the fact that the linked inheritance of characters is manifestation of localization of the genes controlling them on one couple of homologous chromosomes.
Between the genes located far apart on one chromosome there can be several decussations (fig. 2). Products of an even number of decussations will be indistinguishable from initial combinations. Therefore for creation of accurate genetic maps resort to consecutive association of rather short sites of chromosomes, on to-rykh multiple decussations are less probable.
Assessment of recombinational distances between linked genes is influenced by an interference of a crossing-over — change of probability of the second event of a crossing-over on the site of a chromosome adjoining a point of the previous decussation in this process of meiosis. As a measure of an interference serves the coefficient of a kointsidention (coincidence) — the relation of frequency of really observed double decussations on the site of a chromosome to their frequency expected on this site for lack of an interference i.e. to the work of frequencies of unary decussations. For lack of an interference the coefficient of a kointsidention is equal to 1. If the happened crossing-over interferes with implementation of the second crossing-over near this locus of the same couple of chromosomes in the same meiosis, then an interference call positive; in this case the coefficient of a kointsidention can have values from zero (an absolute interference) up to the sizes close to unit. If the first crossing-over increases probability of the second that happens less often, then speak about negative interference (coefficient of a kointsidention more than 1).
Distances between genes on genetic maps are not strictly proportional to physical distances between them on chromosomes, but the sequence of an arrangement of genes in both cases same. It is caused by the unequal frequency of a crossing-over in different sites of chromosomes. E.g., on okolotsentro-dimensional heterochromatic sites of chromosomes the crossing-over usually (but not at all objects) on one unit of physical length of a chromosome happens less than in euchromatic sites.
The meiotic crossing-over leading to formation of recombinant gametes causes combinative genotypic variability (see) also provides all intraspecific genetic variety and formation (but also disintegration) koadaptirovanny gene complexes. Inversions of chromosomes can interfere with recombinational disintegration of already arisen gene complexes (see. Inversion ), especially blocked, eurysynusic at heterozygotes in natural populations of nek-ry species.
Along with meiotic also the mitotic crossing-over occurring in somatic cells and leading to emergence of clones of recombinant cells is possible, to-rye can be shown by mosaicism on the corresponding signs. The meiotic crossing-over occurs in a pro-phase I of meiosis when chromosomes are presented by four chromatids, at the same time recombine only two, as a rule, not sisterly, chromatids. Actually exchange of genetic material is preceded by a rupture of chromatids though it is impossible to exclude also the mechanism of exchange by periodic change of matrixes in the course of DNA replication of chromosomes (cm. Replication ).
Necessary premises of the correct (strictly equal) crossing-over is conjugation of chromosomes (see), at a cut loci of chromosomes precisely «identify» each other so that only strictly homologous sites of chromosomes come into contact. At molecular level specificity of conjugation of chromosomes in meiosis is provided, on-vidimokhmu, with existence in composition of DNA of chromosomes of a large number short (approximately on 100 nucleotides everyone) the sequences of so-called zigotenny DNA (ZDNK), quite evenly and all chromosomes which are often distributed on all length. To a stage of a lepto-tena all DNA of chromosomes, except ZDNK, doubles and forms the super-spiralizovannye threads connected with histones (see), and ZDNK comes into contact on all length of two conjugating chromosomes. At the beginning of a stage of a zigotena the specific protein capable to untwine double helixs of DNA which is not connected with histones appears. Thus, ZDNK untwines and by means of hydrogen bindings forms with ZDNK of a homologous chromosome hybrid double helixs — heteroduplexes. Their education happens strictly complementary, and they consistently extend on length of the conjugating chromosomes. In parallel there is an education a so-called sinapto-a little complex, to-ry consists of two longitudinal proteinaceous tyazhy and fine cross protein fibers. This complex provides fixing of chromosomes in the provision of homologous conjugation and at the same time interferes with their irreversible adhesion. In the zigotena ZDNK heteroduplexes break up, and ZDNK is replicated.
Inversions of chromosomes, especially multiple blocked inversions, interfere with R. of chromosomes since multiple distinctions in the sequences of genes of a usual chromosome and its inverted homolog do not give the chance to the inverted chromosomes specifically to conjugate on all length. Chromosomes with multiple inversions received the name zapirate-leu of decussation. They are widely used in the genetic analysis, for the prevention of reorganization of the tested chromosomes.
The main anomalies of R. of chromosomes are the unequal crossing-over and conversion of genes. The unequal crossing-over arises quite seldom and is usually dated for a certain locus a chromosome where conjugation, happens not strictly homologously, and about a nek-eye shift. The reason of such shift is not clear yet. As a result of an unequal crossing-over one krossoverny chromosome bears doubling (duplication) of the site between points of a rupture of homologs, and in other krossoverny chromosome there is deletion of this site. Though such disturbances can not always be confirmed cytologic, functionally they are close to microscopically detectable cases duplications (see) and deletions (see), are known in medical genetics as partial trisomies and monosomies. In some cases Such anomalies of chromosomes can be the cause chromosomal diseases (see). There is also an idea that duplication of genes and sites of chromosomes with the subsequent independent mutirovaniyekhm each of duplicates serves as the important mechanism of evolutionary complication of genetic systems. In the course of a gametogenesis at heterozygotes like Aa hmozht to occur formation of products of meiosis not in a usual ratio 2a:2a, and in the ratio FOR: 1a though on the next closely linked loci the ratio 2:2 remains. Such phenomenon is called conversion of genes. Experimentally conversion of genes manages to be observed only at mushrooms. Existence and value of conversion of genes at other organisms is almost not studied.
Except the exchange of not sister chromatids characteristic of meiotic and mitotic R., both in meiosis, and in a mitosis there can be sisterly chromatid interchanges found only at differential identification (coloring, an isotope tag) of sister chromatids.
The recombination at bacteria
R.'s Process at bacteria has the nek-ry features connected with specificity of their genetic organization, forms of genetic exchange and functioning of systems of genetic regulation (see. Bacteria, genetics of bacteria ). Genetic material of a bacterial cell is presented by the ring molecule DNA having length apprx. 1000 microns and a configuration of a superspiral. Such molecule is capable to self-copying — replications (see), functioning at the same time as independent unit (replicon) under control of genetic system of regulation. Besides, at cells of many bacteria there are additional ring molecules DNA, small by the sizes — plasmids (see), episomes (see), capable to River. At genetic exchange between various bacteria only the fragment of a chromosome of a donor cell usually gets to a retsi-piyentny cell that leads to formation of partially diploid (merodiploidny) zygotes whereas plasmid replicons are transferred completely. After completion of transfer of genetic material in the created merodiploidny re-tsipiyentny cells (zygotes) process of a recombination begins, to-ry on the mechanism reminds a crossing-over of chromatids of the conjugating homologous chromosomes of eukaryotes. However at R. at bacteria ring molecule DNA of a bacterium recipient (endogenous genetic material) and, on the other hand, the exogenous fragment of molecule DNA of the donor transferred to this bacterium participates in this process, on the one hand. Process begins with a synapse, i.e. with formation of connection between an exogenous fragment of DNA and a certain site of endogenous ring molecule DNA, about the Crimea this fragment has homologous sites. Assume that in these parts there are decussations of two interacting structures, after to-rymi in places of decussations to a certain frequency there is a rupture of molecules and the subsequent «wrong» reunion of their broken-off ends. Inclusion of this or that fragment is result of it (or several various fragments) exogenous genetic material in structure of endogenous ring replicon the recipient - ache a bacterial cell that provides a possibility of further copying of the included fragment (fragments). The opposite (reciprocal) endogenous fragment of DNA of a cell recipient at a crossing-over turns into exogenous extra chromosomal structure» loses ability to be copied and therefore it is lost by a bacterial cell at the subsequent its divisions. As a result of R. of this kind which received the name of a classical or general recombination from a merodiploidny zygote there are daughter haploid cells (recombinants) with these or those combinations of allelic genes of parent genetic structures.
Classical R. at bacteria is possible not only between any replicon and egonereplitsiruyushcheysya a part (a fragment of this replicon), but also between two various full-fledged replicons (a chromosome and a plasmid, a chromosome and a bacteriophage, two plasmids etc.) if in structure of their DNA there are homologous sites. Such R. can result exchange of genetic material between the reacting replicons or association (cointegration) of two interacting replicons by gaps and reunions of molecules DNA in places of a mutual homology with formation of one larger dvureplikonny system, and the plasmid having properties of an episome can be included with a certain frequency of chromosomal replicon in the course of R. in homologous sites of these structures and the long time to be replicated as a part of uniform (double) replicon under control of chromosomal replikativny system. However a small part of the bacterial cells of population containing double replicon has repeated R. leading to return of the integrated plasmid to an autonomous state. If the site of a homology is involved in repeated R., to-ry at primary R. served as the place of interaction of two structures, then there is rather correct «cutting» plasmid replicon from composition of double replicon. In cases when repeated R. occurs in other sites of a homology, inclusion nek-ry of adjacent chromosomal genes in composition of plasmid replicon is possible, i.e. there is a formation of the «replaced» plasmid (fig. 3). The same mechanism leading to cointegration of two replicons and to exchange of sites of genetic material at their subsequent dissociation takes place probably and in case of R. of two various plasmids possessing homologous sites of DNA (fig. 4), and also plasmids and nek-ry bacteriophages or bacteriophages and chromosomes. All stages of classical R. at bacteria are provided with the corresponding enzymes (so-called Iyes-fermentami), and designate this type P. also as River Kes-zavisimaya.
Along with classical, or general R. at bacteria the «illegal» recombination has a wide spread occurance, for implementation the cut is not required to a considerable homology of DNA of the interacting structures. The small fragments of DNA which received the name of the translocated elements participate in such R. to-rye are capable to move with a certain frequency from one replicon to another, migrating among bacterial chromosomes, plasmids, bacteriophages, etc. (see. Translokation ). Two types of such elements — IS elements (English insertion sequences the inserted sequences) and transposons are known. IS elements represent the specific fragments of DNA containing probably only those genes to-rye are necessary for R. with nonhomologous sites of various replicons. This R. leads to integration of such genes into structures of these replicons or to «cutting» the respective sites from such structures. However specific mechanisms of such R. remain not clear. At integration of IS elements and their «cutting» there can be mutations of various genes connected with reorganizations (deletions, inversions, duplications, etc.) respective sites of molecule DNA. Transposons represent more complex structures containing usually in the structure IS elements to-rye and provide their «illegal» R., and the supplementary genes which are not connected with functions of integration (genes of medicinal stability of bacteria, etc.).
Classical and «illegal» R. of bacteria provide ample opportunities of genetic exchange between various replicons and their parts that defines high rates of variability and evolution of these structures and bacterial populations in general in the conditions of intensive use of various antibacterial substances and influences (antibiotics, salts of heavy metals, the ultra-violet and ionizing radiations etc.). In case of the classical R. demanding a considerable homology of the interacting structures, these processes are most effective at intraspecific genetic exchange whereas «illegal» R. plays an important role in redistribution of genes not only within separate types, but also between bacteria of different types and childbirth. Assume also that as a result of inclusion of identical IS elements and transposons in nonhomologous sites of replicons of bacteria of different types there are so-called hot spots of R., i.e. regions of a mutual homology of these replicons providing the subsequent classical R. between them in conditions of both intraspecific, and trans-species exchange of genetic material. In microbiology R.'s processes are used for receiving hybrid forms of bacteria with the changed virulent, antigenic and other properties. Also the methods of creation of artificial recombinants of molecules DNA from the fragments received with the help restriktaz making fundamentals of modern genetic engineering are developed. Thus, new recombinant replicons (plasmids, bacteriophages) can be designed, the structure to-rykh contains the genes including received from metaphytes, which are of practical interest (e.g., the genes controlling synthesis of certain hormones, vitamins, amino acids, antibiotics, etc.). After administration of such replicons in suitable bacterial cells these cells can be used in the medical industry and other areas mikrobiol. productions for receiving the corresponding biologically active agents. Spontaneous R. is resulted by also various atypical forms pathogenic and opportunistic pathogenic bacteriums.
R.'s frequency can fluctuate considerably depending on a number of factors. At classical R. process is capable to be broken significantly because of a low homology of the interacting molecules, and also at mutations of the genes controlling River. Low degree of a homology of DNA of chromosomes at bacteria of different types and childbirth serves as the main reason for low frequency of R. of these structures at interspecific and bigeneric crossing. However re-using of the received recombinants in crossings can increase R.'s frequency due to increase of such homology. The mutations causing loss of functional activity of the genes controlling R. lead a bacterial cell to full or partial loss of ability to carry out classical R., and also reduce its ability to reparations of genetic damages (see). R.'s processes at bacteria significantly are influenced also by environmental factors (composition of nutrient medium, temperature, ultraviolet and ionizing radiation, various chemical substances, etc.).
For R.'s studying at bacteria physical use radio biological, electronic and microscopic and others. - chemical methods of a research, and also methods genetic analysis (see) bacteria. Various methods of determination of frequency of R. of linked genes are the cornerstone of genetic mapping of bacteria.
A recombination of viruses — see. Viruses .
Bibliography: Shaving with l of ER of S. E. Molecular biology, page 305, JI., 1973, bibliogr.; Gershenzon S. M. Fundamentals of modern genetics, page 93, Kiev, 1979; To at sh e in V. V. Mechanisms of a genetic recombination, L., 1971, bibliogr.; M e fi - not l of l of. Bacterial plasmids, the lane with English, page 33, etc., M., 1976, bibliogr.; Recombinant molecules, under the editorship of R. Bierce and E. Besit, lane with English, M., 1980, bibliogr.; Physiological genetics, under the editorship of M. E. Lobashev and S. G. Inga-Vechtomov, page 129, etc., L. „1976, bibliogr.; Heys U. Genetika of bacteria and bacteriophages, the lane with English, page 257, 476, etc., M., 1965; Cytology and genetics of meiosis, under the editorship of V. V. Hvostova and Yu. F. Bogdanov, M., 1975.
V. I. Ivanov; V. P. Pinches (bakt.).