BIOCHEMICAL GENETICS

From Big Medical Encyclopedia

BIOCHEMICAL GENETICS — the section of genetics studying mechanisms of genetic control of biochemical processes was selected in the independent direction upon transition of genetic researches to molecular level. B. studies: chemical nature of a gene; molecular «sense» of record of genetic information; molecular «sense» of mutations and recombinations at the level of a gene; mechanisms of transfer of genetic information in the course of proteinaceous synthesis and regulation of this process; molecular nature of formation of an ancestral feature. An object of a research B. of are all live organisms from a virus to the person inclusive. B.'s methodology of is based on set of the genetic and biochemical principles of a research [methods genetic analysis (see), methods of molecular biology during the studying of expression of signs, methods of chemistry of proteins for studying of the sequence of amino acids in them and clarification of nature of damage of proteins at hereditary pathology etc.].

The first data proving biochemical distinction between individuals were received by K. Landshteyner (1900) on the example of biochemical specificity of blood groups at the person. A bit later, in 1909, A. Garrod published the monograph «Inborn Errors of Metabolism», having laid thereby the foundation for B. of diseases of the person. A. Garrod opened the chemical nature alkaptonurias (see), having shown that with urine of patients with this disease alkapton is emitted (homogentistic to - that). Patients with this disease are homozygous carriers of couple of mutant recessive genes (see. Mendel laws ), defining insufficiency of enzyme of an oxidase homogentistic to - you.

A critical stage in B.'s development by was use of microorganisms as objects of a research. Advantage of microorganisms to genetic researches is defined by the following circumstances: a) one-celled structure; b) speed of change of generation that allows to study the genetic events proceeding with a low frequency (a recombination, transformation); c) an opportunity to analyze at the same time large number of individuals; d) exclusive simplicity of cultivation and selection on artificial mediums, and also existence of haploid set of chromosomes. Philosophy of studying of the nature of bacterial mutants were offered by Bidl and Teytem (G. W. Beadle, E. L. Tatum, 1941). Object of their researches — a mold of a neurodispute — can grow on the minimum environment, i.e. the Wednesday consisting only of water, some salts and glucose only in that case when any of ways of her metabolism was not blocked as a result of any mutational change. If such mutation arises, then growth is possible on condition of addition on the minimum Wednesday of substance, synthesis to-rogo is blocked. Varying the substances added to the minimum environment, it is possible to define in what of chain links of biosynthesis this mutant has a disturbance.

From 68 000 strains neurodisputes Bidl and Teytem allocated 380 mutants, the majority of which for the growth was demanded or different amino acids and vitamins, or predecessors of biosynthesis of nucleic acids. Biochemical identification of these mutants allowed to find out the main stages of synthesis of amino acids, sugars, nucleic acids etc. It is possible to give studying of a chain of biosynthesis of arginine as an example. It is known that at mammals predecessors of biosynthesis of arginine are ornithine and citrulline. In experiences with various argininedependent mutants neurodisputes it is established that one of them grow on the Wednesday with ornithine and citrulline, and others — only with citrulline. Therefore, the sequence of synthesis of arginine shall be following: ornithine — citrulline — arginine.

On the basis of similar experiments Bidl and Teytem formulated one of philosophy of B. of: «one gene — one enzyme», i.e. each biochemical sign of an organism is genetically determined, and synthesis of each enzyme (protein) is controlled by a certain gene. Later this formulation was specified: «one gene — one polypeptide chain» since synthesis of the enzymes and not fermental proteins (hemoglobin) consisting of several polypeptide subunits is coded by several genes. For these works Bidl and Teytem were conferred the Nobel Prize.

For studying of metabolism of some biologically important connections, in particular vitamins and pigments, auxotroph mutants are widely used (see. Auksotrofny microorganisms ). Auxotroph mutants of colibacillus in a number of the countries found application for identification of a number of hereditary diseases for the person. D. M. Goldfarb (1968) offered a method of use of auxotroph mutants for total check of newborns on excess presence at their blood of some amino acids. If on the minimum environment, the cut is applied on a surface a drop of the studied material, growth of mutants, dependent on some amino acid, is noted, then it indicates presence at material of amino acid and consequently, and on disturbance of amino-acid exchange at newborns. Various level of dependence of mutants on amino acid allows to judge approximately amount of amino acid in material. If necessary the child is exposed to more detailed inspection (see. Guthrie method ).

, Basic for B., the question of a stseplennost of genes which products of activity make a uniform chain of biosynthesis was. The American scientist F. Hartman showed that the genes controlling biosynthesis of a histidine are located on the genetic map as it should be, approximately corresponding to stages of its biosynthesis. However compliance between a stseplennost of genes and proximity of chain links of biosynthesis is not the firm rule both for microorganisms, and for the highest animals, including the person. The phenomenon of group of genes formed a basis for a conclusion that genes in an organism work well-coordinated and their functioning is regulated in time.

Function of the genes (called structural) is regulated by products of other genes designated as regulatory. The sum of structural and regulatory genes makes the functional unit which received the name operon (see).

Synthesis of a polypeptide chain includes two main stages — transcription (see) genetic information and it broadcasting (see). Genetic information is written down in molecules DNA in the form of the specific sequence of four nucleotides. According to J. Watson's model and T. Shout of DNA consists of two anti-parallel chains designated as right and left (see. Deoxyribonucleic acid ). The chain of DNA, about a cut is carried out writing off of genetic information, call transcribed. In different genes of transcribed there can be both a right, and left chain of DNA. Transition of a transcription from one chain of DNA to another is one of ways of regulation of action of genes. The basic possibility of existence of such regulation is for the first time proved by the Soviet scientific R. B. Hesin (1962).

Great success of B. of is connected with clarification of molecular bases of hereditary pathology at the person. E.g., it is shown that the change in hemoglobin leading to drepanocytic anemia is caused by replacement in a β-chain of the changed hemoglobin of the amino-acid rest glutaminic to - you on amino acid valine (see Hemoglobin, the Hemoglobinopathy). Are already identified at the level of separate amino-acid replacements of 98 dot mutations in polypeptide chains of haemo globins.

One of problems of B. of is allocation and studying of individual genes, and also their laboratory synthesis. Purely lactose operon of colibacillus [Bekvit with sotr was succeeded to allocate. (I. Beckwith u. and.)]. The possibility of such allocation is based that two different nekomplementarny transdutsiruyushchy phages (see. Transduction ) included the same site of bacterial in composition of the DNA genome (see), in this case the operon coding synthesis of lactose. After that DNA of these phages became complementary, but only on the included site (see. Mutational analysis ). Using this circumstance, it was succeeded to be exempted from nekomplementarny material and to allocate a pure operon. In further researches it was succeeded to allocate separate genes of synthesis of ribosomal RNA (r-RNA) and acceptor RNA (t-RNK).

Allocation of individual genes of the higher organisms is more difficult task since DNA of these organisms contain many genes. However in the cells synthesizing specific proteins it was possible to emit information RNA (i-RNK), complementary a nek-eye to genes. For the first time pure i-RNK it was allocated from unripe erythrocytes which 95% of proteinaceous synthesis are the share of hemoglobin. In structure of some viruses (e.g., in a virus of a myeloblastosis of birds) specific enzyme which in certain conditions was capable to synthesize DNA on complementary to it RNA was found. These achievements allowed to carry out (1972) enzymatic synthesis of an individual gene of the higher organism by means of a RNA-dependent DNA polymerase on a matrix i-RNK hemoglobin [Baltimore and Spiegelman (D. Baltimore, S. Spiegelman)].

New and very perspective direction of modern biology began to develop in a crust, time on the basis of B. — genetic engineering (see), putting the task searches of ways of treatment of hereditary diseases by introduction of «healthy» genes (see. Gene therapy ).

In the USSR research according to B. is conducted at departments of biochemistry and pediatrics of medical institutes, at departments of biochemistry of universities, in laboratories of biochemical genetics of research institutes. Most widely researches on B. of are conducted in Ying-those the general genetics of Academy of Sciences of the USSR, institutes of experimental medicine and medical genetics of the USSR Academy of Medical Sciences, in Ying-those cytology and genetics FROM Academy of Sciences of the USSR. General-theoretical questions B. of are developed in a number specialized biol, and chemical institutes.

Abroad according to B. research in specialized biochemical and clinical laboratories at universities and hospitals. In ChSSR — Ying t of organic chemistry and biochemistry, in France — the National center of scientific research, in the USA — Ying t of molecular biology, Massachusetts technological in-t, and also some other scientific centers and universities.

In England questions B. of are developed in the specialized centers (The Galton Laboratory, London; The London Hospital Medical College).

See also Bacteria (genetics), Viruses (genetics), Genetics .


Bibliography: Topical issues of modern genetics, under the editorship of S. I. Alikhanyan, M., 1966; Wagner R. F. and Mitchell of X. K. Genetika and a metabolism, the lane with English, M., 1958, bibliogr.; Heys U. Genetika of bacteria and bacteriophages, the lane with English, M., 1965; G and of about d A. E. Inborn errors of metabolism, L., 1963; Harris H. An introduction to human biochemical genetics, Cambridge, 1953; about N of e, The principies of human biochemical genetics, Amsterdam — L., 1970, bibliogr.

Periodicals — Genetics, M., since 1965; Achievements of modern genetics, M., since 1967; Annals of Human Genetics, JI., since 1956 (1940 — 1955 — Annals of Eugenics); Biochemical Genetics, N. Y., since 1967; Clinical Genetics, Copenhagen, since 1970; Genetical Research, L., since 1960; Genetics, Baltimore, since 1916.

Yu. P. Vinetsky, S. I. Gorodetsky.

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