What is studying molecular biology. Item, tasks and objectives of molecular biology

Molecular biology / m ə. l.ɛ toJ.ʊ l.ər. / It is a branch of biology, as regards the molecular basis of biological activity between biomolecules in various cell systems, including the interactions between DNA, RNA, proteins and their biosynthesis, as well as the regulation of these interactions. Write B. nature In 1961, Astbury described the molecular biology:

Not so much technique as an approach, an approach from the point of view of the so-called fundamental sciences with the leading idea of \u200b\u200bfinding below large-scale manifestations of classical biology for the corresponding molecular plan. He is concerned in particular, with forms Biological molecules and [...] mostly three-dimensional and structurally - which does not mean, however, that this is just a clarification of morphology. It must at the same time explore the genesis and functions.

Attitude to other biological sciences

Researchers in the field of molecular biology use specific methods of growing molecular biology, but more and more combine them with methods and ideas from genetics and biochemistry. There is a non-defined line between these disciplines. This is shown in the following scheme, which depicts one possible type of relationship between fields:

Biochemistry is the study of chemicals and vital processes in living organisms. Biochemists are hard to focus on the roles, functions and structures of biomolecules. The study of chemistry for biological processes and synthesis of biologically active module with examples of biochemistry.
Genetics is the study of the influence of genetic differences in organisms. This can often be removal of the normal component (for example, the gene). The study of "mutants" is organized by one or more functional components with respect to the so-called "wild type" or normal phenotype. Genetic interactions (epistasis) are often confused by simple interpretations of such "knockout" studies.
Molecular biology It is the study of the molecular basics of replication, transcription, translation and cell functioning processes. The central dogma of molecular biology, where the genetic material is transcribed in RNA and then translated into the protein, despite the extensive, still provides a good starting point for understanding the field. The picture was revised in the light of the emerging new RNA roles.

Methods of molecular biology

Molecular cloning

One of the most basic methods of molecular biology to study the protein function is molecular cloning. In this technique, DNA encoding a protein that is of interest cloned with a polymerase chain reaction (PCR), and / or restriction enzymes in plasmid (expression vector). The vector has 3 distinctive features: the start of replication, and the multiple cloning site (MCS), and the selective marker, as a rule, with resistance to antibiotics. The multiple cloning site above is promoter areas and initiation transcriptions that regulate the expression of the cloned gene. This plasmid can be inserted into either bacterial or animal cells. The administration of DNA into bacterial cells can be done by transforming with absorption of bare DNA, conjugations using intercellular contacts or by transduction using a viral vector. The introduction of DNA into eukaryotic cells, such as animal cells, with physical or chemical means, is called transfection. Several different transfection methods are available, such as transfection phosphate, electroporation, microinjection and liposomal transfection. The plasmid can be integrated into the genome, which leads to a stable transfection, or it may remain independent of the genome, called transient transformation processes.

DNA encoding proteins of interest, currently inside the cell, and proteins, can now be expressed. A variety of systems, such as inducible promoters and specific cellular signaling factors that will help express the interest of protein at high levels. Large amounts of protein can then be extracted from a bacterial or eukaryotic cell. Protein can be checked for enzymatic activity in different situations, protein can be crystallized therefore its tertiary structure can be studied, or in the pharmaceutical industry, the activity of new drugs against protein can be studied.

Polymerase chain reaction

Macromolecules Blotting and Study

Terms northern , west and oriental Blotting gets from what was originally molecular biology joke that played on the term Sarewnet After the technique described by Edwin Southern for the Blotted DNA hybridization. Patricia Thomas, RNA developer - blotting, which was then famous as northern - Blottling , not really use this term.

SauterNibotting

Named in honor of his inventor, Biologist Edwin South, then Sarew - Blot is a method for studying for the presence of a specific DNA sequence in a DNA sample. DNA samples before or after restriction enzyme (restrictasis) digestions are separated by electrophoresis in the gel, and then transferred to the membrane using blotting using a capillary action. The membrane is then exposed to labeled DNA - probe, which has a base sequence to addition to a sequence on DNA of interest. Southern Blotting is less widely used in the scientific laboratory due to the ability of other methods, such as PCR, to detect DNA specific sequences from DNA samples. These blots are still used for some applications, however, such as the transgene measurement of the number of copies in transgenic mice or in the engineering of the gene of knockout lines of embryonic stem cells.

Northern Blottling

Northern Blot Chart

East Blotting

Clinical studies and medical treatment methods arising from molecular biology are partially covered by gene therapy. The use of molecular biology or molecular cell biology of approaches in medicine is now called molecular medicine. Molecular biology also plays an important role in the understanding of education, actions and regulations of various parts of cells, which can be used to effectively target new drugs, disease diagnosis and understand cell physiology.

Profession in persons

Maria Shitova

Daria Samoilova

Alexey Grachev

Molecular biology in the field of oncology is a perspective professional direction, as the fight against cancer is one of the priorities of world medicine.

Molecular biologists are in demand in many areas in connection with the active development of science, biotechnological and innovative enterprises. To date, there is a small deficit of specialists, especially those who have a certain experience in the specialty. Until now, quite a large number of graduates continues to leave to work abroad. Now the possibilities of effective work in the field of biotechnology in Russia are beginning to appear, but it is too early to speak about the mass.

The operation of a molecular biologist prevents the active participation of a specialist in scientific activities, which becomes a mechanism for career advancement. Development in the profession is possible through participation in scientific projects and conferences, it is possible through the development of adjacent areas of knowledge. Also, there is also an academic development from a junior researcher through a senior researcher to a leading scientific employee, professor and / or head of the department / laboratory.

interview

Sergei Pirogov - participant of preparations for the biology of biology organized by "elephant and giraffe" in 2012
Winner of the International Universiade on Biology
Winner of Lomonosov Olympiad
The winner of the regional stage of the All-Russian Biology Olympiad in 2012
Learn to Moscow State University. M.V. Lomonosov at the Biological Faculty: The Department of Molecular Biology, on the 6th course. It works in the laboratory of biochemical genetics of animals of the Institute of Molecular Genetics.

- Seryozha, if the readers have questions, they will be able to ask them?

Yes, of course, you can ask questions at least immediately. In this field:

Click to ask a question.

- Let's start with the school, did you seem to be not a supercourse school?

I studied at a very weak Moscow school school, such an average school. True, we had a wonderful teacher on MHC, thanks to which we had a large nominal "art historical" orientation of the school.

- What about biology?

We had a very old elderly biology, a deaf and sharp woman, whom everyone was afraid. But love for her subject did not add. Since my childhood, I was passionate about biology, from five years. I read everything myself, mainly fond of anatomy and zoology. So school subjects existed in parallel with my own interests. All changed the Olympics.

- Tell me more about it.

In grade 7, I first took part in the municipal stage (of course, immediately almost in all subjects, because I was the only student whom the teachers had the grounds to send). And became the winner of biology. Then the school reacted to it as a funny, but not too interesting fact.

- Did it help you at school?

I remember that despite the brilliant study, it was often obtained from the teacher on the biology of the fourths with the soldiers like "in the figure of the cut of the bulb of the root should be painted brown, and not gray." All this was quite depressing. In the 8th grade, I again went to the Olympics, but for some reason I did not send me on biology. But became the winner and prize for other subjects.

- What was in grade 9?

In grade 9 did not go to the district stage. There, I unexpectedly scored the weak, the borderline point, which turned out to be a passage to the regional stage. It had a powerful motivating force - awareness of how much it turns out I don't know how many people, all this know (how many such people on the scale of the country I was even afraid to imagine).

- Tell me how you were preparing.

Intensive independent lesson, raids on bookstores and thousands of last year's tasks have been a healing effect. I scored one of the largest points for the theory (which was also completely sudden to me), went to the practical stage ... and failed him. At that time, I still did not know about the existence of a practical stage.

- did the Olympiad affect you?

My life has changed radically. I learned about many other Olympics, especially loved Sko. Subsequently, many showed good results, some won, thanks to Lomonosov, received the right to enter without exams. In parallel, I won the Olympics on the history of the art, to which I was unevenly breathing and so on. True, it was not friendly with practical tours. In the 11th grade, I still got to the final stage, but Fortune was not favorable and this time I did not have time to fill the matrix of responses theoretical stage. But it allowed not to worry much for practical.

- You met with many olympodics?

Yes, I still believe that I was very lucky with the circle of my peers, pretty expanded my horizons. Another side of the Olympics, in addition to motivation, more harmoniously study the subject was acquaintance with the Olympiadons. Already at that time I noticed that horizontal communication is sometimes more useful than vertical - with teachers at the charges.

- How did you enter the university? Choose the faculty?

After grade 11, I entered the Biofak MSU. Just most of my then comrades made a choice in favor of the FBB, but then the priority role was played by the fact that I did not become the winner of Osteros. So I would need to take the internal exam in mathematics, and in it, especially the school - the highest I loved much more - I was not strong. And at school there was very weak preparation (we did not even prepare for almost the whole). In terms of interest, then I guess that, ultimately, you can come to any result, regardless of the place of receipt. Subsequently, it turned out that there are a lot of FBI graduates who were moving in preferably wet biology, and vice versa - many good bioinformatics began with lovers. Although at that moment it seemed to me that the contingent was not as an example of a weaker FBBSH. In this, I certainly became mistaken.

Did you know?

interesting

Did you know?

interesting

In the elephant camp and the giraffe there are shifts on biochemistry and molecular biology, where schoolchildren with experienced teachers from Moscow State University are experiments, and are also preparing for the Olympiads.

© Interview Prew Denis Rakes. Photos kindly provided Sergey Piroggers.

The development of biochemistry, biophysics, genetics, cytochemistry, many sections of microbiology and virology at about the beginning of the 40s of the XX century. closely led to the study of life phenomena at the molecular level. The successes achieved by these sciences at the same time from different sides led to awareness of the fact that it was at the molecular level that the main management systems of the body function and that the further progress of these sciences will depend on disclosure biological functions Molecules constituting the body of organisms, their participation in the synthesis and decay, mutual transformations and reproduction of compounds in the cell, as well as the energy and information exchange occurring. So at the junction of these biological disciplines with chemistry and physics there was a completely new industry - molecular biology.

In contrast to biochemistry, the attention of modern molecular biology is concentrated mainly on the study of the structure and function of the most important classes of biopolymers - proteins and nucleic acids, the first of which determine the possibility of flowing exchange reactions, and the second - biosynthesis of specific proteins. Therefore, it is clear that it is impossible to carry out a clear distinction between molecular biology and biochemistry, corresponding sections of genetics, microbiology and virology.

The emergence of molecular biology was closely related to the development of new research methods, which have already been said in the relevant chapters. Along with the development of electron microscopy and other methods of microscopic technology, the methods of fractionation of cell elements developed in the 50s were played a major role. They were based on advanced differential centrifugation methods (A. Claud, 1954). By this time there were already quite reliable methods for the allocation and fractionation of biopolymers. This includes, in particular, proposed by A. Tizelius (1937; Nobel Prize, 1948) method of fractionation of proteins using electrophoresis, methods for washing and purifying nucleic acids (E. Key, A. Downs, M. Sevag, A. Mirsky, and others. ). In parallel, in many laboratories of the world, various methods of chromatographic analysis were developed (A. Martin and R. Sing, 1941; Nobel Prize, 1952), subsequently improved significantly.

An invaluable service in decoding the structure of biopolymers was played by X-ray structural analysis. The basic principles of X-ray structural analysis were developed at the Royal College of the University of London under the leadership of W. Bregga by a group of researchers, which included J. Bernal, A. Londsdale, W. Astbury, J. Robertson, etc.

The studies of the Professor of the Moscow State University A. R. Kizel on the Biochemistry of Protoplasma (1925 - 1929), who had the most important importance for the subsequent formation of molecular biology were noted. Kizel inflicted a blow to a firmly rooted representation, which is based on any protoplasm of a special protein body - plates, as if determining all its most important structural and functional features. He showed that the plates are a protein that is found only in mixomycetes, and then at a certain stage of development, and that there is no permanent component - a single skeletal protein - in protoplasm does not exist. Thus, the study of the problem of the structure of the protoplasma and the functional role of proteins came to the right path and received space for its development. Research from Kizel won world recognition by stimulating the study of the chemistry of the components of the cell.

The term "molecular biology" for the first time used by the English crystallograph of the professor of the University of W. Astbury, probably appeared at the beginning of the 40s (until 1945). The fundamental X-ray diffraction studies of proteins and DNAs conducted by Astbury in the 1930s served as the basis for the subsequent successful decoding secondary structure These biopolymers. In 1963, J. Bernal wrote: "The monument will be set by the whole molecular biology - the science he called and really founded" *, in the literature, this term appeared for the first time, perhaps in 1946 in the article W. Astbury "Progress of X-ray structural Analysis of organic and fibrillar compounds "published in the English magazine" Nature "**. In his Greenwaite lecture, Astbury (1950) was noted: "I am pleased that now the term molecular biology is already quite widely used, although it is not possible that I first suggested him. I liked him and I was trying to distribute it for a long time." ***. Already in 1950, Astbury was clear that molecular biology is of the case primarily with the structure and conformation of macromolecules, the study of which is crucial for understanding the functioning of living organisms.

* (Biogr. Mem. FELLOWS ROY. Soc, 1963, V. 9, 29.)

** (W. T. Astbury. Progress of X-Ray Analysis of Organic and Fiber Structures.- Nature,. 1946, v. 157, 121.)

*** (W. T. Astbury. Adventures in Molecular Biology. Thomas Springfield, 1952, p. 3.)

In front of the molecular biology, they stood, in fact, the same tasks as in front of the entire biology as a whole - the knowledge of the essence of life and its basic phenomena, in particular, such as heredity and variability. Modern molecular biology is primarily intended to decipher the structure and function of genes, paths and mechanisms for implementing genetic information of organisms at different stages of ontogenesis and at different stages of its reading. It is designed to open the subtle mechanisms for regulating the activity of genes and cell differentiation, to find out the nature of mutagenesis and the molecular bases of the evolutionary process.

Establishment of the genetic role of nucleic acids

For the formation of molecular biology, the following discoveries had the greatest value. In 1944, American researchers O. EVERI, K. Mac-Lodoz (Nobel Prize, 1923) and M. Mac-picture showed that the DNA molecule isolated from pneumococcis possess transforming activity. After the hydrolysis of these DNA, the deoxyribonuclease, their transforming activity completely disappeared. Thus, it was convincing that it was DNA with genetic functions in the cell, and not a protein.

For the sake of fairness, it should be noted that the phenomenon of bacterial transformation was detected significantly earlier than the opening of the Ever, Mac-Leod and the Mac-picture. In 1928, F. Griffith published an article in which he said that after adding to unwariable (non-regulated) pneumococcal cells of the capsulated virulent strain, the resulting cell mixture becomes destructive for mice. Moreover, the living cells infected with this mixture of animals infected with this mixture were already virulent and possessed a polysaccharide capsule. Thus, in this experiment, it was shown that under the influence of some components of the killed cells of pneumococci cells, a noncapsulated form of bacteria turns into a capsule-forming virulent form. 16 years later, EVERE, MAC-CEO and Mac-Powered replaced in this experience killed whole cells of pneumococci their deoxyribonucleic acid and showed that it is DNA that has a transforming activity (see also chapters 7 and 25). The value of this discovery is difficult to overestimate. It stimulated the study of nucleic acids in many laboratories of the world and forced to concentrate the attention of scientists on DNA.

Along with the discovery of EVER, Mac-Loda and the Mac-picture, by the beginning of the 50s, a rather large number of direct and indirect data has already accumulated that nucleic acids play an exceptional role in life and carry a genetic function. This, in particular, also indicated the nature of the Localization of DNA in the cell and the data of R. Vendrelli (1948) that the DNA content on the cell is strictly constantly and correlates with the degree of fluity: in the haploid genual cells of DNA half less than in diploid somatic. In favor of the genetic role of DNA, its pronounced metabolic stability also testified. By the beginning of the 50s, many diverse facts have accumulated that most of the known mutagenic factors act mainly on nucleic acids and, in particular, on DNA (R. Childikiss, 1949; Efrussi-Taylor, 1951; E. Friz , 1957, etc.).

Of particular importance in the establishment of the genetic role of nucleic acids was the study of various phages and viruses. In 1933, D. Schlesinger found DNA in the bacteriophage of intestinal sticks. Since the allocation of W. Wenni (1935, Nobel Prize, 1946) tobacco mosaic virus (VTM) in the crystalline state began new stage In the study of plant viruses. In 1937 - 1938 Employees of the Rotamwed Agricultural Station (England) F. Bouden and N. Piri showed that many plant viruses allocated by them are not globulin, but are ribonucleotoids and contain nucleic acid as an obligatory component. At the very beginning of the 40s, the work of the city of Scramma (1940), P. A. Agatova (1941), Miller and Wenley (1941) were published (1941), indicating that the noticeable chemical modification of the protein component does not lead to The loss of VTM infectiousness. This indicated that the protein component could not be a carrier of the hereditary properties of the virus, as many microbiologists continued to be considered. Compeferable evidence in favor of the genetic role of nucleic acid (RNA) in plant viruses was obtained in 1956 by the scramm in Tubingen (Germany) and X. Frankel-Constant in California (USA). These researchers were almost simultaneously allocated from VTM RNA and showed that it was it, and not a protein, it has infectiousness: as a result of infection of tobacco plants of this RNA, they have been forming and reproduction of normal viral particles. This meant that RNA contains information for the synthesis and assembly of all viral components, including a viral protein. In 1968, I. G. Atabekov found that the protein plays a significant role in the very infection of plants - the nature of the protein determines the range of host plants.

In 1957, Frankel Const, for the first time, carried out the reconstruction of the WTM from the components of its components - RNA and protein. Along with normal particles, he received mixed "hybrids", in which RNA was from one strain, and protein from another. The heredity of such hybrids was fully determined by RNA, and the offspring of viruses belonged to that strain whose RNA was used to obtain the initial mixed particles. Later experiments A. Girera, Shuster and Schramma (1958) and Vitman (1960 - 1966) showed that the chemical modification of the nucleic component of VTM leads to the emergence of various mutants of this virus.

In 1970, D. Baltimore and Tehin found that the transfer of genetic information can occur not only from DNA to RNA, but on the contrary. They found in some oncogenic RNA-containing viruses (oncornaviruses) a special enzyme, the so-called reverse transcriptase, which is capable of complementary to the RNA circuits to synthesize DNA. This major discovery made it possible to understand the labeling mechanism in the genome of the genetic information of RNA-containing viruses and look at the nature of their oncogenic action in a new way.

Opening of nucleic acids and the study of their properties

The term nucleic acid was introduced by the German biochemist R. Altman in 1889, after these compounds were opened in 1869 by the Swiss physician F. Misher. Misher extracted the cells of the pus diluted with hydrochloric acid for several weeks and received almost pure nuclear material in the remainder. This material he considered the characteristic "substance of cell nuclei and called it nuclease. In terms of its properties, Nuclein differed sharply from the proteins: he was more sour, did not contain sulfur, but it was a lot of phosphorus, he was well soluble in alkalis, but did not dissolve in Diluted acids.

The results of their observations over Nuclein Misher sent F. Goppe Zapeler to publish in the journal. The substance described was so unusual (at that time only lecithin was known from all biological phosphorus-containing compounds) that Goppe-Zayler did not believe the experiments of Misher, returned to him the manuscript and instructed his employees N. Poelosh and N. Lubavin to check his conclusions on another material . The work of Misher "On the Chemical Composition of Moose Cells" was published in two years later (1871). At the same time, the work of the Hoppe Zapeler and his staff about the composition of the cells of the pus, erythrocytes of birds, snakes and other cells were published. Over the next three years, nuclein has been isolated from animal cells and yeast.

In his work, Misher noted that a detailed study of different nucleicins could lead to the establishment of differences between them, thereby anticipating the idea of \u200b\u200bthe specificity of nucleic acids. Exploring salmon milk, Misher found that Nuclein is in them in the form of salt and is associated with the main protein, which he called Protamot.

In 1879, A. Kossel began to study A. Kossel in the Labpe-Zapeler laboratory. In 1881, he allocated hypoxanthine from Nuclein, but at that time he still doubted the origin of this foundation and believed that hypoxantine could be a product of protein degradation. In 1891, among the products of Nucleein's hydrolysis, Kossel discovered adenine, guanine, phosphoric acid and another substance with sugar properties. For research on the chemistry of nucleic acids Kososhel in 1910, the Nobel Prize was awarded.

Further successes in deciphering the structure of nucleic acids are related to the studies of P. Levin and employees (1911 - 1934). In 1911, P. Levin and V. Zhakobs identified the carbohydrate components of adenosine and guanosine; They found that D-Ribose enters these nucleosides. In 1930, Levin showed that a carbohydrate component of deoxyribonucleoside is 2-deoxy-D-ribose. It became known from its work that nucleic acids are constructed from nucleotides, i.e. phosphorylated nucleosides. Levin believed that the main type of communication in nucleic acids (RNA) is 2 ", 5" -phosphodieter communication. This representation turned out to be erroneous. Thanks to the works of the English chemist A. Todd (Nobel Prize, 1957) and its employees, as well as English biochemists R. Markham and J. Smith in the early 50s it became known that the main type of communication in RNA is 3 ", 5" - Phosphodieter communication.

Levin showed that different nucleic acids may differ by the nature of the carbohydrate component: some of them contain sugar deoxyribose, and others - ribose. In addition, these two types of nucleic acids differed by nature of one of the bases: in nucleic acids of pentosular type contained uracil, and in the nucleic acids of deoxyptentotic type - Timin. Deoxypenomic nucleic acid (according to modern terminology, deoxyribonucleic acid - DNA) is usually easily isolated in large quantities of the thymus (oil gland) of calves. Therefore, it obtained the name of thimonucleic acid. The source of nucleic acid of the pentosular type (RNA) served mainly yeast and proprietary wheat. This type was often called yeast nucleic acid.

At the beginning of the 30s, the presentation was quite firmly rooted, as if nucleic acid of yeast type was characterized, and thimonucleic acid is characteristic only of animal cell nuclei. Two types of nucleic acids - RNA and DNA - at that time were called with vegetable and animal nucleic acids accordingly. However, as previous studies have shown, A. N. Belozersky, such a division of nucleic acids is unjustified. In 1934, Belozersky first discovered thimonucleic acid in herbal cells: he allocated the pea seedlings and identified the Timin-pyrimidine base characteristic of DNA. He then discovered Timin and other plants (soybean seeds, beans). In 1936, A. N. Belozersky and I. I. Dubrovskaya allocated preparative DNA from Soviet Castana seedlings. In addition, a series of works performed in the 40s in England D. Davidson with employees convincingly showed that plant nucleic acid (RNA) is contained in many animal cells.

The widespread use of the Rosenbeck (1924) of the cytochemical reaction to DNA and the RNA reaction (1924) (1944) on RNA was developed pretty quickly and unambiguously resolve the question of the preferential localization of these nucleic acids in the cell. It turned out that DNA is concentrated in the kernel, while RNA is mainly concentrated in the cytoplasm. Later it was found that RNA is contained both in the cytoplasm and in the core, and in addition, cytoplasmic DNA were revealed.

As for the question of the primary structure of nucleic acids, by the mid-40s, the presentation of P. Levin was firmly established in science, according to which all nucleic acids are constructed by one type and consist of the same so-called tetranucleotide blocks. Each of these blocks, according to Levin, contains four different nucleotides. The tetranucleotide theory of the structure of nucleic acids largely deprived these biopolymers of specificity. Therefore, it is not surprising that all the specifics of the lively linked at that time only with proteins, the nature of the monomers of which is much more diverse (20 amino acids).

The first breach in the theory of the tetranucleotide structure of nucleic acids broke through analytical data of the English chemist J. Gullanda (1945 - 1947). When determining the composition of nucleic acids on nitrogen base, it did not receive an equimolar base ratio, as it should be according to Levin theory. The finally tetranucleotide theory of the structure of nucleic acids collapsed as a result of research by E. Chargaff and its employees (1949 - 1951). For the separation of bases whipped from DNA as a result of its acidic hydrolysis, Chargaff used chromatography on paper. Each of these bases was accurately defined spectrophotometrically. Charguff noticed significant deviations from the equimolar ratio of the bases in DNA of various origins and for the first time definitely stated that DNA has a pronounced species specificity. Thus, it was finished with hegemony concept about protein specificity in a living cage. Analyzing DNA of various origins, CHARGAF discovered and formulated the unique patterns of DNA composition, included in science called Chargaff rules. According to these rules, in all DNA, regardless of origin, the amount of adenine is equal to the amount of thymine (A \u003d T), the amount of guanin is equal to the amount of cytosine (r \u003d c), the amount of purines is equal to the amount of pyrimidines (g + a \u003d c + t) The bases with 6-amino groups are equal to the amount of bases with 6-keto-mutual (A + C \u003d r + T). At the same time, despite such strict quantitative correspondences, DNA of different species differ in terms of ratio A + T: G + C. In some DNA, the number of guanin and cytosine prevails over the amount of adenine and timin (these DNA Chargaff called DNA Hz-type); Other DNAs contain adenine and thymine more than guanin and cytosine (these DNAs were named AT-type DNA). DNA data obtained by Chargaff played an exceptional role in molecular biology. It was them that they were based on the opening of the structure of DNA made in 1953. J. Watson and F. Screech.

Back in 1938, W. Astbury and F. Bell, with X-ray structural analysis, showed that the foundations plane in DNA should be perpendicular to the long axis of the molecule and reminded the stack of plates lying on each other. As the technique of X-ray structural analysis is improved by 1952 - 1953. Information has accumulated, which allowed to judge the length of individual connections and tilt corners. This made it possible with the greatest probability to present the nature of the orientation of the rings of pentosular residues in the sucrophosphate bone of the DNA molecule. In 1952, S. Farberg suggested two speculative DNA models, which represented a folded or twisted molecule itself. At least the speculative model of the structure of DNA was proposed in 1953 L. Polingom (Laureate of the Nobel Prize, 1954) and R. Corey. In this model, the three-swirled DNA circuits formed a long spiral, the rod of which was represented by phosphate groups, and the base was located outside it. By 1953, M. Wilkins and R. Franklin received clearer X-ray paintings of DNA. Their analysis showed the complete inconsistency of Ferberg, Poling and Corey models. Using Chargaff data, comparing different combinations of molecular models of individual monomers and x-ray analysis data, J. Watson and F. Creek in 1953 came to the conclusion that the DNA molecule should be a cheaper spiral. Chargaff Rules have sharply limited the number of possible ordered combinations of bases in the proposed DNA model; They suggested Watson and the cry that in the DNA molecule should be a specific mating of bases - adenine with thimine, and guanin with a cytosine. In other words, adenine in one DNA circuit always strictly corresponds to Timin in another chain, and guanin in one chain necessarily corresponds to cytosine in another. Thus, Watson and Creek first formulated the exceptional importance of the principle of the complementary structure of DNA, according to which one DNA chain complements the other, that is, the sequence of bases of one chain uniquely determines the base sequence in another (complementary) chain. It became obvious that already in the structure of DNA, the potential for its accurate playback is laid. This model of the structure of DNA is currently generally recognized. For decoding the structure of DNA cries, Watson and Wilkins in 1962, the Nobel Prize was awarded.

It should be noted that the idea of \u200b\u200bthe mechanism of accurate reproduction of macromolecules and the transfer of hereditary information originated in our country. In 1927, N, K. Koltsov suggested that during the reproduction of cells there is a reproduction of molecules by accurate autocatalytic reproduction of the existing mother molecules. True, at that time, the rings endowed this property of the DNA molecule, but the protein nature molecules, the functional value of which was not known then. Nevertheless, the thought itself on the autocatalytic reproduction of macromolecules and the transmission mechanism of hereditary properties was a prophetic: it became the leading idea of \u200b\u200bmodern molecular biology.

A. N. Belozersky, A. S. Spirin, G. N. Zaitseva, B. F. Vanyushin, S. O. Uryson, A. S. Antonov and other long-term research (1957-1974) DNA composition diverse st different organisms Completely confirmed the patterns discovered by Chargaff, and complete correspondence with the molecular model of the structure of DNA proposed by Watson and Cry. These studies have shown that DNA of different bacteria, mushrooms, algae, actinomycetes, higher plants, invertebrates and vertebrates have the specificity of the composition. Particularly sharply differences in the composition (content of at-AT-Couples) are expressed in microorganisms, turning to an important taxonomic sign. At higher plants and animals, species variations in DNA are expressed significantly weaker. But this does not mean that the DNA is less specific. In addition to the composition of grounds, specificity is largely determined by their sequence in DNA chains.

Along with conventional bases, additional nitrogenous bases were found in the composition of DNA and RNA. Thus, in the composition of the DNA of plants and animals, White (1950) found 5-methylcitozin, and D. Dunn and J. Smith (1958) discovered in some DNA methylated adenine. For a long time, methylcitozin was considered a distinctive feature of the genetic material of higher organisms. In 1968, A. N. Belozersky, B. F. Vanyushin and N. A. Kokurin found that he could also meet in DNA bacteria.

In 1964, M. Gold and J. Hurvitz opened a new class of enzymes that carry out the natural modification of DNA - its methylation. After that, the discovery was clear that the minor (contained in small quantities) of the base arise already on the finished polynucleotide chain of DNA as a result of a specific methylation of cytosine and adenine residues in special sequences. In particular, according to B. F. Vanyushina, Ya. I. Burnanova and A. N. Belozersky (1969) Methylization of adenine in the DNA of the intestinal stick can occur in the terminal codons. According to A. N. Belozersky and employees (1968 - 1970), as well as M. Meselson (USA) and V. Arberry (Switzerland) (1965 - 1969), methylation gives DNA unique individual traits and in combination with the action of specific nucleus Part of the complex mechanism that monitors the synthesis of DNA in the cell. In other words, the nature of methylation of one or another DNA predetermines the question of whether it can multiply in this cell.

Almost at the same time, the allocation and intensive study of DNA methylas and restricting endonucleases began; In 1969 - 1975 Nucleotide sequences recognized in DNA are established by some of these enzymes (X. Boyer, X. Smith, S. Lynn, K. Murray). In the hydrolysis of different DNA, the restricant enzyme is spacing quite large fragments with the same "sticky" ends. This makes it possible not only to analyze the structure of genes, as is done in small viruses (D. Natans, S. Adler, 1973 - 1975), but also design various genomes. With the opening of these specific restriction enzymes, genetic engineering has become a tangible reality. Built into small plasmid DNA genes of various origin is already easily introduced into various cells. Thus, a new type of biologically active plasmid, giving resistance to some antibiotics (C. Cohen, 1973), was introduced by ribosomal genes of frogs and drosophila in the plasmids of the intestinal sticks (J. Morrow, 1974; X. Boyer, D. Hognes, R. Devis , 1974 - 1975). Thus, real paths are open to obtain fundamentally new organisms by administering and embedding in their gene pool a variety of genes. This discovery can be directed to the benefit of all mankind.

In 1952, White and S. Cohen found that the T-even phage DNA contains an unusual base - 5-oxymethyl excitosis. Later, E. Wolkina and R. Sinsheimer (1954) and Cohen (1956) (1954) and Cohen (1956) began that the residues of oxymethyl excitement can be fully or partially glucosidated, as a result of which the phage DNA molecule turns out to be protected from hydrolytic action of nucleases.

In the early 50s, D. Dunna and J. Smith (England), S. Vychlohof (USA) and A. Vacra (Germany) became known that many artificial analogues of the grounds may be included in DNA, sometimes to 50% Timine. As a rule, these substitutions lead to errors in replication, transcription of DNA and broadcast and to the appearance of mutants. So, J. Marmour (1962) found that in DNA of some phages, instead of thymine, it contains oxymethyluracyl. In 1963, I. Takahashi and J. Marmour found that the DNA of one of the phages instead of Timin contains uracil. Thus, another principle collapsed in which nucleic acids were previously separated. Since the work of P. Levin, it was believed that the distinctive feature of DNA is Timin, and RNA - Uracil. It became clear that this sign is not always reliable, and the principal difference in the chemical nature of the two types of nucleic acids, as it appears today, serves only the character of the carbohydrate component.

When studying the phages, many unusual signs of organic nucleic acids were opened. Since 1953, it was believed that all DNAs are juggling linear molecules, and RNA is only single-drawn. This provision was substantially shaken in 1961, when R. Sinsheimer found that the phage DNA φ x 174 is represented by a single-flowing ring molecule. True, then it turned out that in this form, this DNA exists only in the vegetative phage particle, and the replicative form of DNA of this phage is also cheating. In addition, it turned out very unexpected that RNA some viruses can be cheating. This new type of Macromolecular RNA organization was discovered in 1962 by P. Homatosome, I. Tamm and other researchers in some animal viruses and a wound tumor virus of plants. Recently, V. I. Agol and A. A. Bogdanov (1970) found that in addition to linear RNA molecules there are also closed or cyclic molecules. Cyclic juggling RNA is detected by them, in particular, in the encephalomeelocarditis virus. Thanks to the works of X. Devo, L. Tokino, T. I. Tikhonenko, E. I. Budovsky and others (1960 - 1974) became the main features of the organization (laying) of genetic material in bacteriophages.

In the late 50s, the American scientist P. Doti found that during heating, DNA denaturation occurs, accompanied by a breakdown of hydrogen bonds between the base pairs and the discrepancy between complementary chains. This process is the character of the phase transition by the type of "Spiral-tangle" and reminds the melting of crystals. Therefore, the process of thermal denaturation DNA DNA has called DNA melting. With slow cooling, the renaturcets of molecules occurs, i.e. reunification of complementary halves.

The principle of renaturation in 1960 was used by J. Marmur and K. Shildkraut to determine the degree of "hybridizability" of DNA of different microorganisms. Subsequently, E. Bolton and B. Mac-picture improved this technique, proposing the method of so-called DNA agar speakers. This method was irreplaceable in studying the degree of homology of the nucleotide sequence of different DNA and the clarification of genetic kinship of different organisms. Open DTO denaturation DNA in combination with the described J. Mandela and A. Hershey * (1960) chromatography on methylated albumin and centrifugation in the density gradient (the method was developed in 1957 M. Meselson, F., and D. Vinogradov) is widely used for separation, discharge and analysis of individual complementary DNA chains, for example, V. Shibalski (USA) using these techniques for separating DNA lambda phage, showed in 1967-1969, which are genetically active are both chains of phage, and not one, as It was considered to be (S. SPigelman, 1961). It should be noted that for the first time the idea of \u200b\u200bthe genetic significance of both chains of DNA Lambda Faga was expressed in the USSR S. E. Bresler (1961).

* (For work on genetics of bacteria and viruses A. Hershi together with M. Delbryuk and S. Luria were awarded in 1969 of the Nobel Prize.)

To understand the organization and functional activity of the genome, the definition of a nucleotide sequence of DNA is of paramount importance. The search for methods of this definition is conducted in many laboratories in the world. In the USA, M. Bir with employees since the end of the 50s, trying to establish a DNA sequence with electron microscopy, but so far unsuccessfully. In the early 50s, the first works of Sinsheimer, Chargaff and other researchers in the enzymatic degradation of DNA became known that different nucleotides in the DNA molecule are distributed, although it is indelically, but uneven. According to the English chemist K. Barton (1961), pyrimidines (more than 70%) are focused mainly in the form of the corresponding blocks. A. L. Mazin and B. F. Vanyushin (1968 - 1969) found that different DNAs have varying degrees of pyrimidine chance and that in DNA of animal organisms, it increases significantly as the lowest to higher. Thus, the evolution of organisms is reflected in the structure of their genomes. That is why for understanding the evolutionary process as a whole, a comparative study of the structure of nucleic acids is of particular importance. Analysis of the structure of biologically important polymers and, first of all, DNA is extremely important for solving many private issues of phylogenetics and taxonomy.

It is interesting to note that the English physiologist E. Lankester, who studied the hemoglobins of mollusks, exactly 100 years ago, anticipating the ideas of molecular biology, wrote: "The chemical differences in various types and genera of animals and plants are as important to clarify the history of their origin, as well as differences in their form. If we could clearly establish differences in the molecular organization and functioning of organisms, we would be able to significantly better understand the origin and evolution of different organisms than on the basis of morphological observations "*. The significance of biochemical studies for the systematics emphasized V. L. Komarov, who wrote that "at the heart of everyone even purely morphological signs, on the basis of which we classify and install species, are precisely biochemical differences "**.

* (E. R. Lankester. Uber Das Vorcommen Von Haemoglobin in Den Muskeln der Mollusken und Die Verbreitung Desselben in Den Lebrendigen Organismen.- "Pfluger" s Archiv Fur Die Gesammte Physiol., 1871, BD 4, 319.)

** (V. L. Komarov. Selected cit., T. 1. M.-L., Publishing House of the Academy of Sciences of the USSR, 1945, p. 331.)

A. V. Blagoveshchensky and S. L. Ivanov still in the 20s took the first steps in our country to clarify some issues of evolution and systematics of organisms based on a comparative analysis of their biochemical composition (see ch. 2). Comparative analysis The structures of proteins and nucleic acids are currently becoming increasingly tangible for systematics (see chapter 21). This method of molecular biology allows not only to clarify the position of individual species in the system, but also forces the principles of the classification of organisms in a new way, and sometimes to revise the entire system as a whole, as it happened, for example, with systematics of microorganisms. Undoubtedly, in the future, the analysis of the structure of the genome will occupy a central place in the chemisystem of organisms.

A great importance for the formation of molecular biology was a decoding of DNA replication and transcription mechanisms (see chapter 24).

Biosynthesis protein

An important shift in solving the problem of protein biosynthesis is associated with success in the study of nucleic acids. In 1941, T. Kasperson (Sweden) and in 1942, J. Brother, drew attention to the fact that in tissues with active protein synthesis, an increased amount of RNA contains an increased amount of RNA. They concluded that ribonucleic acids play a decisive role in protein synthesis. In 1953, E. Gale and D. Fox, as if received direct evidence of the direct participation of RNA in the biosynthesis of protein: according to their data, ribonuclease significantly suppressed the inclusion of amino acids in bacterial cell lysates. V. Alfrei, M. Delhi and A. Mirsky (1953) on liver homogenates were obtained. Later, E. Gale refused to give them the right idea about the leading RNA role in protein synthesis, erroneously believing that the activation of protein synthesis in the cell-free system was influenced by some other substance of unknown nature. In 1954, P. Prince, D. Litlfield, R. B. Hesin-Lurie and others found that the most active inclusion of amino acids occurs in rich RNA fractions of subcellular particles - micros. P. Signing and E. Keller (1953 - 1954) found that the inclusion of amino acids was noticeably intensified in the presence of the supernatant fraction in the conditions of ATP regeneration. P. Sichevitz (1952) and M. Chogland (1956) was isolated from the supernatant protein fraction (pH 5 fraction), which was responsible for the sharp stimulation of the inclusion of amino acids in microscoms. Along with the proteins in the supernatant, a special class of low molecular weight RNA was discovered, which are now called transport RNA (TRNA). In 1958, the chogland and a selection, as well as P. Berg, R. Svit and F. Allen and many other researchers found that their special enzyme, ATP and specific TRNA were needed to activate each amino acid. It became clear that TRNA was performed solely by the function of adapters, i.e. the devices that are found on the nucleic matrix (IRNK) the place of the corresponding amino acid in the forming protein molecule. These studies have fully confirmed the adapter hypothesis F. Creek (1957), which envisaged the existence of polynucleotide adapters in the cell, necessary for the correct arrangement of the amino acid residues of the synthesized protein on the nucleic matrix. Already a lot of later French scientist F. Shapvil (1962) in the laboratory F. Lipman (Nobel Prize, 1953) in the United States very witty and unequivocally showed that the location of the amino acid in the synthesizing protein molecule is fully determined by the specific TRNA, to which it is attached. The adapter cryothesis of the cry was developed in the works of a chogland and a selection.

By 1958, the following main stages of protein synthesis were known: 1) activation of amino acids with a specific enzyme from "pH 5 of the fraction" in the presence of ATP to form aminoacyalatelative; 2) the attachment of activated amino acid to a specific TRNA with the release of adenosine monophosphate (AMP); 3) Combination of aminoacyl-TRNA (TRNA, loaded with amino acid) with microsomes and the inclusion of amino acids in the TRNA release protein. Chogland (1958) noted that at the last stage of protein synthesis, guangoosintrifosphate (GTF) is necessary.

Transport RNA and gene synthesis

After the TRNA is detected, active search for their fractionation and determination of the nucleotide sequence began. American biochemist R. Holly achieved the greatest advantages. In 1965, he established the structure of Alanin TRNA from yeast. With the help of ribonuclease (guanilla RNA-AZA and pancreatic RNA-AZA), the Holly divided the nucleic acid molecule into several fragments, determined in each of them a nucleotide sequence and then reconstructed the sequence of the entire Alanine TRNA molecule. This path of analysis of the nucleotide sequence was named block method. The merit of Holly consisted mainly in the fact that he learned to divide the RNA molecule not only into small pieces, as many did it to him, but also on large fragments (quarters and halves). This gave him the opportunity to properly assemble individual small pieces together and thereby recreate the complete nucleotide sequence of the entire TRNA molecule (Nobel Prize, 1968).

This reception was immediately adopted in many laboratories in the world. Over the next two years in the USSR and abroad, a primary structure of several TRNA was decrypted. A. A. Baev (1967) and employees first established a sequence of nucleotides in yeast valve TRNA. To date, more than a dozen different individual TRNA has already been studied. A kind of record in determining the nucleotide sequence is established in Cambridge F. Senger and Brownley. These researchers have developed an amazingly elegant method of separating oligonucleotides and installed the sequence of so-called 5 S (ribosomal) RNA from the cells of the intestinal sticks (1968). This RNA consists of 120 nucleotide residues and, unlike TRNA, does not contain additional minor bases, which significantly facilitate the analysis of the nucleotide sequence, serving the unique reference points of individual fragments of the molecule. Currently, thanks to the use of the Senger and Browni method, work is successfully promoted to study the sequence of long ribosomal RNA and some viral RNA in the Laboratory of J. Ebel (France) and other researchers.

A. A. Baev and Employees (1967) found that the Valin TRNA dusted in half restores its macromolecular structure in solution and, despite the defect in the primary structure, has the functional activity of the initial (native) molecule. This approach is the reconstruction of the cut macromolecules after removing certain fragments - it turned out to be very promising. It is widely used now to find out the functional role of individual sections of certain TRNA.

In recent years, a great success has been achieved in obtaining crystalline preparations of individual TRNA. Now in several laboratories in the United States and England managed to crystallize many TRNA. This made it possible to investigate the TRNA opposite with X-ray structural analysis. In 1970, R. side presented the first radiographs and three-dimensional models of several TRNA, created by him at Wisconsin University. These models help to determine the localization of individual functionally active sites in TRNA and understand the basic principles of the functioning of these molecules.

The most important importance for the disclosure of the protein synthesis mechanism and solving the problem of the specificity of this process was to decipher the nature of the genetic code (see Chapter 24), which, without exaggeration, can be considered as the leading conquest of natural science XX century.

The disclosure of R. Holly of the primary structure of TRNA gave impetus to the works of the city of the Quran * (USA) on the synthesis of oligonucleotides and sent them to the path of the synthesis of a certain biological structure - the DNA molecule encoding the alanic TRNA. The first steps of the chemical synthesis of short oligonucleotides were made almost 15 years ago ended in 1970. For the first time by the initiative of the gene. The Koran and his staff first from individual nucleotides were synthesized by chemicals by short fragments with a length of 8-12 nucleotide residues. These fragments with a given nucleotide sequence have formed spontaneously cheerful complementary pieces with overlapping in 4 - 5 nucleotides. Then these finished pieces in the desired order alternately connected an end to the end using the DNA ligase enzyme. Thus, in contrast to the replication of DNA molecules, according to A. Cornberg ** (see chapter 24), the Quran managed to re-create a natural jug-free DNA molecule according to a predetermined program in accordance with the TRNA sequence described by Holly. Similarly, work is underway on the synthesis of other genes (M. N. Kolosov, 3. A. Shabarova, D. G. Knorre, 1970 - 1975).

* (For research of the genetic code, the city of Koran and M. Nirereberg was awarded in 1968 the Nobel Prize.)

** (For the opening of polymerase and synthesis of DNA A. Kornberg, and for the synthesis of RNA S. Ochoa in 1959 was awarded the Nobel Prize.)

Microsomes, ribosomes, broadcast

In the mid-50s it was believed that the center of protein synthesis in the cell is microsomes. The term microsoma was first introduced in 1949 by A. Claude to designate the fraction of small granules. It later it turned out that the entire fraction of a microson, consisting of membranes and granules, was responsible for protein synthesis, but only small ribonucleoprotoid particles. These particles in 1958 were called R. Roberts Ribosomes.

Classic studies of bacterial ribosomes were held by A. Tisier and J. Watson in 1958 - 1959. Bacterial ribosomes were somewhat smaller than plant and animals. J. Littleton (1960), M. Clark (1964) and E. N. Sveta (1966) showed that the ribosomes of chloroplasts of higher plants and mitochondria belong to the bacterial type. A. Tisier and others (1958) found that the ribosomes are dissociated by two unequal subunits containing one molecule of RNA. In the late 50s it was believed that each ribosomal RNA molecule consists of several short fragments. However, A. S. Spirin in 1960 first showed that RNA in sub-fullets are represented by a continuous molecule. D. Waller (1960), dividing ribosomal proteins using electrophoresis in the starch gel, found that they are very heterogeneous. At first, many doubted the data of Waller, since it seemed that the ribosome protein should be strictly homogeneous as, for example, VTM protein. Currently, as a result of research by D. Waller, R. Tratu, P. Traub and other biochemists became known that more than 50 completely different in the structure of proteins became part of the ribosomal particles. A. S. Spirina In 1963, it was possible for the first time to deploy Ribosomal subconsists and show that ribosomes are compactly twisted ribonucleoprote-shaft, which in certain conditions can be deployed. In 1967 - 1968 M. Nomura has completely reconstructed a biologically active subpartigin from ribosomal RNA and protein and even received such ribosomes in which protein and RNA belonged to different microorganisms.

Until today, the role of ribosomal RNA is unclear. It is assumed that it is the unique specific matrix, on which, in the formation of a ribosomal particle, it finds a strictly defined place each of the many ribosomal proteins (A. S. Spirin, 1968).

A. Rich (1962) discovered aggregates from several ribosomes interconnected by the IRNN thread. These complexes were called polisms. Policy detection allowed Rich and Watson (1963) to express the assumption that the synthesis of the polypeptide chain occurs on the ribosome, which is moving along the IRNK chain. As the ribosomes are promoted along the IRNN chain in the particle, the information and the formation of the protein polypeptide chain is performed, and the new ribosomes alternately join the released read end of the IRNK. From these Richa and Watson, it followed that the value of the cell in the cell consists in mass production of protein by consistently reading the matrix at several ribosomes at once.

As a result of research M. Nirenberg, S. Ochua, F. Lipman, Korana and others in 1963 - 1970. It became known that along with IRNA, ribosomes, ATP and aminoacyl-TRNA in the transmission process takes part a large number of diverse factors, and the broadcast process itself can be conditionally divided into three stages - initiation, actually broadcast and termination.

The translation initiation means the synthesis of the first peptide bond in the ribosome complex - the matrix polynucleotide - aminoacyl-trading. Not any aminoacyl-TRNA, but formylmethionyl-TRNA, has such initiatorial activity. This substance was first allocated in 1964 by F. Senger and K. Marker. S. Barencher and K. Marker (1966) showed that the initiator function of formylmethionyl-TRNA was due to its increased affinity for the peptidal center of the ribosome. To start broadcasting, some protein initiation factors are also extremely important, which were highlighted in the Laboratories of S. Ochoa, F. Gro and other investigative centers. After the formation of the first peptide connection in the ribosome, the broadcast itself begins, i.e., the sequential addition of the aminoacyl residue to the C-end of the polypeptide. Many details of the broadcasting process were studied by K. Monroe and J. Bishop (England), I. Rykhlik and F. Shorm (Czech Republic), F. Lipman, M. Baretcher, V. Gilbert (USA) and other researchers. In 1968, A. S. Spirin, to explain the mechanism of work of the Ribosome, proposed the original hypothesis. The drive mechanism providing all spatial movements of TRNA and IRNN during the broadcast is periodic opening and closure of ribosome subchains. The end of the broadcast is encoded in the most readable matrix that contains termination codons. As S. Brenner (1965 - 1967) showed, such codons are UAA, UAG and UGA driplets. M. Capinchi (1967) also revealed special protein termination factors. A. S. Spirin and L. P. Gavrilova described the so-called "non-fermented" synthesis of protein in ribosomes (1972 - 1975) without the participation of protein factors. This discovery is important for understanding the origin and evolution of protein biosynthesis.

Regulation of the activity of genes and proteins

After the problem of the specificity of protein synthesis in the first place in the molecular biology, the problem of regulating proteins synthesis, or, is the same, the regulation of the activity of genes.

The functional non-uniformity of the cells and the reprisals associated with it and the activation of the genes have long attracted the attention of geneticists, but until recently the real mechanism for controlling genetic activity remained unknown.

The first attempts to explain the regulatory activity of genes were associated with the study of histonian proteins. More spouse Stadman * at the beginning of the 40s of the XX century. They expressed the idea that it was Histons that could play a major role in this phenomenon. In the future, they received the first clear data on differences in the chemical nature of histone proteins. Currently, the number of facts testifying to this hypothesis, every year increasingly growing.

* (E. STEDMAN, E. STEDMAN. The Basic Proteins of Cell Nuclei.- Phylosoph. Trans. Roy. SOC. London, 1951, V. 235, 565 - 595.)

At the same time, an increasing number of data speaking is that regulation of gene activity is a much more complex process than a simple interaction of genes of genes with molecules of histone proteins. In 1960 - 1962 In the laboratory, R. B. Hesin-Lurie It was found that the phage genes begin to be read upstream: the Phage T2 genes can be divided into early, the functioning of which occurred in the first minutes of infection of the bacterial cell, and the late, starting to synthesize the IRNK after the completion of the early genes.

In 1961, French Biochemists F. Jacob and J. Mono proposed a scheme for regulating gene activity, which played an exceptional role in the understanding of the regulatory mechanisms of the cell at all. According to the jacob and mono scheme, in the DNA, in addition to structural (information) genes, there are still gements-regulators and genes-operators. The gene-regulator encodes the synthesis of a specific substance - the repressor, which can be joined both to the inductor and the gene operator. The generator is connected with structural genes, and the gear gene is at some distance from them. If there is no inductor in the environment, for example, lactose, the repressor synthesized by the regulator gene is binding to the operator gene and, blocking it, turns off the operation of the entire operon (block of structural genes along with the operator managers). The formation of the enzyme under these conditions does not occur. If inductor (lactose) appears in the medium, then the product of the genetic regulator - the repressor is associated with lactose and removes the block from the generator gene. In this case, the work of the structural gene encoding the synthesis of the enzyme is becoming possible, and the enzyme (lactose) appears in the medium.

According to Jacob and Mono, this regulation scheme is applicable to all adaptive enzymes and may occur both during repression, when the formation of the enzyme is suppressed by an excess of the reaction product and during induction, when the substrate contributes to the synthesis of the enzyme. For research regulation of the activity of Jacob genes and Mono, the Nobel Prize was awarded in 1965.

Initially, this scheme seemed too far-fetched. However, it later turned out that the regulation of genes on this principle takes place not only in bacteria, but also in other organisms.

Since 1960, a noticeable place in molecular biology is occupied by the study of the organization of the genome and the structure of chromatin in eukaryotic organisms (J. Bonner, R. Britten, V. Olfry, P. Walker, Yu. S. Chentsov, I. B. Zbarsky and others .) And by regulation of transcription (A. Mirsky, P. Georgiev, M. Burnistil, D. Gall, R. Tsanguev, R. I. Salganik). For a long time, there was an unknown and controversial nature of the repressor. In 1968, M. Ptashne (USA) showed that the repressor is protein. He highlighted him in the laboratory of J. Watson and found that the repressor, indeed, has affinity for the inductor (lactose) and at the same time "recognizes" the Lac Opero generator generator and specifically communicates with it.

In the last 5 - 7 years, data was obtained on the presence of another managing cell of gene activity - promoter. It turned out that in the neighborhood with the operator site, to which the product is joined, synthesized at a controlled gender - protein substance of the repressor, there is another area, which should also be attributed to members of the regulatory system of gene activity. The RNA polymerase enzyme molecule is attached to this area. A mutual recognition of a unique sequence of nucleotides in DNA and a specific configuration of the RNA polymerase protein must occur in the promotional portion. The effectiveness of the recognition will depend on the implementation of the process of reading genetic information with this sequence of opera genes adjacent to the promoter.

In addition to the jacob and mono scheme described, there are other generation mechanisms in the cell. F. Jacob and S. Brenner (1963) found that the regulation of replication of bacterial DNA is defined by a cell membrane. Experts of Jacob (1954) on the induction of various opposies convincingly showed that, under the influence of various mutagenic factors, the electoral replication of the program gene begins, and the replication of the host genome is blocked. In 1970, F. Bell reported that small DNA molecules can be passed into the cytoplasm of the kernel and there are already transcribed there.

Thus, the regulation of the activity of genes can be carried out at the level of replication, transcription and broadcast.

Significant success is achieved in the study of the regulation not only the synthesis of enzymes, but also their activity. The phenomena of the regulation of the activity of enzymes in the cell was indicated in the 1950s A. Novik and L. Szilllard. Ushubarger (1956) found that in the cell there is a very rational way to suppress the activity of the enzyme by the final product of the feedback reaction chain. As was established by J. Mono, J. Shange, F. Jacob, A. Padi and other researchers (1956 - 1960), the regulation of enzyme activity can be carried out by Alosteric principle. The enzyme or one of its subunits, except affinity for the substrate, has affinity for one of the reaction chain products. Under the influence of such a product-signal, the enzyme changes its conformation, which loses its activity. As a result, the entire chain of enzymatic reactions turns off at the very beginning. On a significant role of conformational changes in protein in enzymatic reactions, and in a certain sense And for the presence of an altoherectic effect, D. Weem and R. Woodward (1952; Nobel Prize laureate, 1965).

Structure and function of proteins

As a result of T. Osborne, Gofmeister, A. Gürbera, F. Schulz and many others at the end of the XIX century. Many animals and vegetable proteins were obtained in crystalline. At about the same time, the molecular weights of some proteins were installed with the help of different physical methods. So, in 1891 A. Sabaneyev and N. Alexandrov reported that the molecular weight of Ovalbumin is 14,000; In 1905, E. Reid found that the molecular weight of hemoglobin is equal to 48,000. The polymer structure of proteins was disclosed in 1871 G. Glazulotz and D. Gaberman. The idea of \u200b\u200bpeptide communication of individual amino acid residues in proteins was expressed by T. Kurtius (1883). Amino acid chemical condensation works (E. Shaal, 1871; Schiff, 1897; L. Balbiano and D. Tracati, 1900) and heteropolypeptide synthesis (E. Fisher, 1902 - 1907, the Nobel Prize, 1902) led to the development of basic principles Chemical structure of proteins.

The first crystal enzyme (ureaza) was obtained in 1926. J. Samner (Nobel Prize, 1946), and in 1930, J. Northrop (Nobel Prize, 1946) received crystalline pepsin. After these works it became clear that enzymes have a protein nature. In 1940, M. Kunitz allocated a crystalline RNA-Azu. By 1958, more than 100 crystalline enzymes were already known and over 500 enzymes allocated in non-crystalline form. The preparation of highly purified drugs of individual proteins contributed to deciphering their primary structure and macromolecular organization.

Of great importance for the development of molecular biology in general, human genetics, especially the discovery of L. Polingom (1940) of abnormal hemoglobin S, isolated from erythrocytes of people with severe hereditary disease - sickle cell anemia. In 1955 - 1957 V. Ingram used the fingerprint method developed by F. Senger (spots formed by individual peptides during paper chromatography) to analyze the hemoglobin hydrolysis products with alkali and trypsin. In 1961, Ingram reported that hemoglobin S differs from normal hemoglobin only by nature of one amino acid residue: in normal hemoglobin in the seventh position of the chain is the residue of glutamic acid, and in the hemoglobin S - the residue of the valine. Thereby fully confirmed (1949), the assumption of poling that the sickle cell anemia is a disease of molecular nature. Inheritable change in only one amino acid residue in each half of the hemoglobin macromolecule leads to the fact that hemoglobin loses the ability to be easily dissolved at a low oxygen concentration and begins to crystallize, which leads to a violation of the cell structure. These studies clearly showed that the protein structure is a strictly defined amino acid sequence that is encoded in the genome. On the exclusive value of the primary structure of the protein in the formation of a unique biologically active conformation of the macromolecule showed the work of K. Anfinsen (1951). Anfinsen showed that the dietary biologically active macrostructure of pancreatic ribonuclease is predetermined by an amino acid sequence and can again occur spontaneously when the cysteine \u200b\u200bsh-groups are oxidized to form disulfide stakes in strictly defined places of the enzyme peptide chain.

To date, the mechanism of action of a large number of enzymes has been studied in detail and the structure of many proteins is determined.

In 1953, F. Senger established an amino acid sequence of insulin. : This protein consists of two polypeptide chains connected by two disulfide stakes. One of the chains contains only 21 amino acid residues, and the other is 30 residues. To decipher the structure of this comparatively simple protein, Senger spent about 10 years. In 1958, for this outstanding study, he was awarded the Nobel Prize. After the creation of V. Stein and S. Murom (1957) of the automatic analyzer of amino acids, the identification of products of partial hydrolysis of proteins was significantly accelerated. In 1960, Stein and Moore have already reported. They managed to determine the sequence of ribonuclease, the peptide chain of which is represented by 124 amino acid residues. In the same year, in the laboratory of the Scramma in Tubingen (Germany) F. Ander and others identified the amino acid sequence in protein VTM. Then the amino acid sequence was determined in Mioglobin (A. Edmunson) and the α- and β-chains of the hemoglobin of a person (Brownitzer, E. Schröder, etc.), Lizozyme from a chicken egg protein (Jullah, D. Keyfield). In 1963, F. Shorm and B. Keyl (Czech Republic) established a sequence of amino acids in the chymotrypsinogen molecule. In the same year, the amino acid sequence of trypsinogen (F. Shorm, D. Walch) was determined. In 1965, K. Takahashi established the primary structure of Ribonuclease T1. Then the amino acid sequence was still defined in several proteins.

As is known, the final proof of the correctness of determining one or another structure is its synthesis. In 1969, R. Merifield (USA) first carried out the chemical synthesis of pancreatic ribonuclease. With the help of a synthesis method developed by it on a solid-separated carrier, Merofield attached one amino acid to the chain by another according to the sequence that was described by the stein and Murom. As a result, he received a protein, which in its qualities was identical to the pancreatic Ribonuclease A. For the disclosure of the structure of Ribonuclease V. Stein, S. Muru and K. Anfinsenu was awarded the Nobel Prize in 1972. This synthesis of natural protein opens up ambitious perspectives, indicating the possibility of creating any proteins in accordance with the planned sequence.

From X-ray diffraction studies, W. Astbury (1933) followed that peptide chains of protein molecules were twisted or strictly strictly laid. Since that time, many authors expressed various hypotheses about the methods of laying protein chains, but until 1951, all models remained as crime constructions that did not meet experimental data. In 1951, L. Poling and R. Corey published a series of brilliant work, in which the theory of the secondary structure of proteins was finally formulated - the theory of α-helix. Along with this, it also became known that proteins have another tertiary structure: the α-helix of the peptide chain can be in a certain way formulated, forming a rather compact structure.

In 1957, J. Kendrew and his staff were first offered a three-dimensional model of the structure of Mioglobin. This model was then refined for several years, while in 1961 there was no final work with the characteristic of the spatial structure of this protein. In 1959, M. Perutz and employees established the three-dimensional structure of hemoglobin. The researchers spent more than 20 years (the first radiographs of hemoglobin were obtained by a truth in 1937). Since hemoglobin molecule consists of four subunits, then deciphering its organization, thereby described the quaternary protein structure for the first time. For work on the definition of the three-dimensional structure of Kendrew proteins and a package in 1962, the Nobel Prize was awarded.

The creation of a spatial model of the hemoglobin structure has allowed. Approach to understand the mechanism of functioning of this protein, which is known to carry out the transfer of oxygen in animal cells. Back in 1937, F. Gaurovitz came to the conclusion that the interaction of hemoglobin with oxygen, air should be accompanied by a change in the structure of the protein. In the 60s, Puertc and his staff discovered a noticeable shift of hemoglobin chains after its oxidation, caused by a shift of iron atoms as a result of binding to oxygen. On this basis, ideas about the "breathing" of protein macromolecules were formed.

In 1960, D. Phillips and its employees began x-ray diffraction studies of lysozyme molecules. By 1967, it was more or less accurate to establish the details of the organization of this protein and the localization of individual atoms in its molecule. In addition, Phillips found out the nature of the attachment of lysozyme to the substrate (triacetylglucosamine). This made it possible to recreate the mechanism of work of this enzyme. Thus, the knowledge of the primary structure and macromolecular organization made it possible not only to establish the nature of the active centers of many enzymes, but also to fully disclose the mechanism of functioning of these macromolecules.

The use of electron microscopy methods helped to disclose the principles of macromolecular organization of such complex protein formations, such as collagen threads, fibrinogen, contractile fibrils of muscles, etc. In the late 50s, models of the muscular contractile apparatus were proposed. The opening of V. A. Engelhardt and M. N. Lyubamova (1939) of ATP-azine activity of myosin was exceptional to understanding the muscular reduction mechanism. This meant that the basis of the act of muscle contraction is the change in the physicochemical properties and macromolecular organization of the contractile protein under the influence of adenosine trifosphoric acid (see also chapter 11).

To understand the principles of assembling biological structures, virological studies were essential (see chapter 25).

Unresolved problems

Basic successes in modern molecular biology are achieved mainly as a result of the study of nucleic acids. Nevertheless, even in this area, not all problems are allowed. Of great effort will require, in particular, deciphering the entire nucleotide sequence of the genome. This problem is in turn inextricably linked to the problem of heterogeneity DNA and requires the development of new fractionation methods and the separation of individual molecules from the total genetic material of the cell.

Until now, efforts were mainly concentrated on a separate study of proteins and nucleic acids. In the cell, these biopolymers are inextricably linked with each other and operate mainly in the form of nucleoproteis. Therefore, now with particular sharpness, the need to study the interaction of proteins and nucleic acids was manifested. The problem of recognition by proteins of certain sections of nucleic acids is put forward to the fore. The steps were already outlined to study such interaction of these biopolymers, without which the complete understanding of the structure and functions of chromosomes, ribosomes and other structures is unthinkable. Without this, it is impossible to also understand the regulation of gene activity and finally decipher the principles of the operation of bodies of whiteoxitheating mechanisms. After the works of Jacob and Mono, some new data on the regulatory meaning of membranes in the synthesis of nuclear material appeared. This puts the task of a deeper study of the role of membranes in the regulation of DNA replication. In general, the problem of regulating the activity of genes and cellular activity in general has become one of the most important problems of modern molecular biology.

The current state of biophysics

In close connection with the problems of molecular biology, biophysics was developed. Interest in this area of \u200b\u200bbiology stimulated, on the one hand, the need for a comprehensive study of action on the body of various generations of radiation, on the other - the need to study the physical and physicochemical foundations of life phenomena occurring at the molecular level.

Obtaining accurate information about molecular structures and processes made in them became possible as a result of the use of new subtle physicochemical methods. Based on the achievements of electrochemistry, it was possible to improve the method of measuring bioelectric potentials, applying ion-electoral electrodes (Eisenman, B. P. Nikolsky, Khuri, 50 - 60s). Infrared spectroscopy (using laser devices) is increasingly in practice, which allows to investigate the conformational changes in proteins (I. carpenters, 1940). The valuable information also provides a method of electron paramagnetic resonance (E. K. Zavoisk, 1944) and a biocular method (B. N. Tarusov et al., 1960), which allow, in particular, to judge the electron transport during oxidative processes.

By the 50s, biophysics conquers a solid position. There is a need to prepare qualified specialists. If in 1911 in Europe only at the University of Pie, in Hungary, was the Department of Biophysics, by 1973 such departments exist in almost all major universities.

In 1960, the international society of biophysicists was organized. In August 1961, the first international biophysical congress in Stockholm took place. The second Congress was held in 1965 in Paris, the third - in 1969 in Boston, the fourth - in 1972 in Moscow.

In biophysics, a clear distinction is maintained between two different contents in the content of molecular biophysics and cell biophysics. This distinction receives and organizational expression: separate departments of these two directions of biophysics are created. At the Moscow University, the first Department of Biophysics was established in 1953 at the Bio-Soil Faculty, a little later, the Department of Biophysics appeared on the physical faculty. According to the same principle, the departments were organized in many other universities.

Molecular biophysical

In recent years, the connection of molecular biophysics with molecular biology has become increasingly strengthened, and it is sometimes difficult to determine where the border of the partition between them passes. In the general occurrence on the problem of hereditary information, such cooperation of biophysics with molecular biology is inevitable.

The main direction in research work is the study of nucleic acid physics - DNA and RNA. The use of the above methods and above all x-ray structural analysis contributed to decomposition of the molecular structure of nucleic acids. Currently, intensive studies are underway to study the behavior of these acids in solutions. Special attention is paid to the conformational transitions of the "Spiral-tangle", studied by viscosity changes, optical and electrical indicators. In connection with the study of mutagenesis mechanisms, studies are developing on the study of the action of ionizing radiation on the behavior of nucleic acids in solutions, as well as the actions of radiation on viruses and phages nucleic acid. The effect of ultraviolet radiation was exposed to comprehensive analysis, some spectral sections of which, as known, are well absorbed by nucleic acids. A large proportion of such studies occupies the detection of active radicals of nucleic acids and proteins by electron paramagnetic resonance. With this method, the occurrence of a whole self-direction is associated.

The problem of encoding DNA and RNA information and its transmission in the synthesis of protein has long been interested in molecular biophysics, and physics have repeatedly expressed certain considerations on this issue (E. Schrödinger, Gamov). The decoding of the genetic code caused numerous theoretical and experimental studies on the structure of the DNA helix, the mechanism of sliding and twisting its threads, to study the physical forces involved in these processes.

Significant assistance to molecular biophysics has molecular biology in the study of the structure of protein molecules using X-ray structural analysis, first applied in 1930 by J. Bernal. It is as a result of using physical methods in combination with biochemical (enzymatic methods) a molecular conformation and a sequence of amino acids in a number of proteins was opened.

Modern electron microscopic studies that revealed the presence of complex membrane systems in cells and its organodes, stimulated attempts to understand their molecular structure (see chapters 10 and 11). The chemical composition of the membranes and, in particular, the properties of their lipids are studied. It was found that the latter are capable of focusing and non-enzymatic chain oxidation reactions (Yu. A. Vladimirov and F. F. Litvin, 1959; B. N. Tarusov et al., 1960; I. Ivanov, 1967) leading to Disruption of membrane functions. To study the composition of membranes began to use also methods mathematical modeling (V. Ts. Presman, 1964 - 1968; M. M. Shemyakin, 1967; Yu. A. Ovchinnikov, 1972).

Cell biophysic

A significant event in the history of biophysics was the formation in the 50s of clear ideas about the thermodynamics of biological processes, as a result of which the assumptions were finally discharged about the possibility of independent energy formation in living cells, contrary to the second law of thermodynamics. Understanding the actions of this law in biological systems is associated with the introduction of the Belgian scientist I. Prigogin (1945) * into biological thermodynamics of the concept of open systems that exchange with an external medium of energy and matter. Prigogin showed that positive entropy is formed in living cells at workflows, respectively, the second law of thermodynamics. The equations introduced by them determined the conditions under which the so-called stationary state occurs (it was also called a dynamic equilibrium), in which the amount of free energy (non-neutrophy) comes into cells with food compensates for its flow, and positive entropy is displayed. This discovery has reinforced the oversized idea of \u200b\u200bthe inseparable coupling of the outer and inner medium of cells. It marked the beginning of a real study of thermodynamics of alive "systems, including modeling method (A. Barton, 1939; A. G. Pasynsky, 1967).

* (The general theory of open systems first put forward L. Bertalafi in 1932)

According to the basic principle of biotermodynamics, the prerequisite for the existence of life is stationary in the development of its biochemical processes, for the implementation of which the coordination of the rates of numerous metabolic reactions is necessary. On the basis of the new biophysical thermodynamics, a direction that allocates external and internal factors that ensure this coordination of reactions and make it stable. Over the past two decades, a large role has been revealed in maintaining the stationary state of the system of inhibitors and especially antioxidants (B. N. Tarusov and A. I. Zhuravlev, 1954, 1958). It has been established that the reliability of inpatient development is related to the factors of the outer environment (temperature) and the physicochemical properties of the cell environment.

Modern principles of biotermodynamics allowed to give physical and chemical interpretation of the adaptation mechanism. According to our data, the adaptation to the conditions of the external environment can occur only if the body can establish stationarity in the development of bio chemical reactions (B. N. Tarusov, 1974). The question arose about the development of new methods that would allow to evaluate the stationary state to be inexplicitably and predict its possible disorders. The introduction of biological adaptation processes of cybernetic principles of self-regulating systems is greatly benefited. It became clear that to solve the question of the stability of the stationary state, the registration of the so-called disturbing factors, to which they relate, in particular, non-enzymatic lipid oxidation reactions. Recently, studies of reproduction processes in lipid phases of living cells and increases of active radical products that violate the regulatory functions of the membranes are increasing increasingly expanding. The source of information on these processes is as detection of active peroxidant radicals and biolypid peroxidation (A. Tappel, 1965; I. I. Ivanov, 1965; E. B. Burlakova, 1967 and others). To detect radicals, biohemoluminescence arising in lipids of living cells during their recombination is used.

Based on the physicochemical representations on the stability of the stationary state, biophysical ideas about the adaptation of plants were arose for changes in the conditions of the external environment as a violation of inhibitory antioxidant systems (B. N. Tarusov, Ya. E. Doskokoch, B. M. Kitlaev, A. M. Aghaverdiev , 1968 - 1972). This opened the opportunity to evaluate such properties such as frost resistance and salt resistance, as well as make appropriate forecasts in the selection of agricultural plants.

In the 50s, an excessive glow was opened - the biological and infrared biological objects in the visible and infrared parts of the spectrum (B. N. Tarusov, A. I. Zhuravlev, A. I. Polyvoda). This became possible as a result of the development of methods for the registration of ultra-plastic light flows with the help of photoelectronic multipliers (L. A. Ketsky, 1934). As the result of biochemical reactions occurring in a living cell, biochemoluminescence allows you to judge important oxidative processes in electron transfer circuits between enzymes. The discovery and study of biochemoluminescence has a large theoretical and practical value. So, B. N. Tarusov and Yu. B. Kudryashov note the greatest role of products of oxidation of unsaturated fatty acids in the mechanism of the occurrence of pathological conditions, developing under the influence of ionizing radiation, during carcinogenesis and other violations normal functions Cells.

In the 50s, due to the rapid development of nuclear physics from biophysics, radiobiology was separated, exploring the biological effect of ionizing radiation. Obtaining artificial radioactive isotopes, the creation of thermonuclear weapons, atomic reactors and the development of other forms of practical use of atomic energy supplied with all the sharpness of the protection of organisms from the harmful effects of ionizing radiation, development theoretical foundations Prevention and treatment of radiation sickness. To do this, it was necessary first of all to find out which components of the cell and the metabolism links are most vulnerable.

The object of studying biophysics and radiobiology was the clarification of the nature of primary chemical reactions arising in living substrates under the influence of radiation energy. It was important here not only to understand the mechanisms of this phenomenon, but also to be able to influence the process of changing physical energy into a chemical, reduce its "useful" action coefficient. Works in this direction were laid on the study of the school N. N. Semenov (1933) in the USSR and D. Khinchelwood (1935) in England.

A large place in radiobiological studies took the study of the degree of radiation resistance of various organisms. It was found that increased radio resistance (for example, desert rodents) is due to the high antioxidant activity of lipids. cell membranes (M. Chang et al., 1964; N. K. Ogryzov et al., 1969). It turned out that in the formation of the antioxidative properties of these systems, tocopherols, vitamin K and thiosion (I. Ivanov et al., 1972) play a major role. In recent years, there are also much attention to the study of mutagenesis mechanisms. For this purpose, the effect of ionizing radiation on the behavior of nucleic acids and in vitro proteins, as well as in viruses and phages (A. Gustafson, 1945 - 1950) is being studied.

The struggle for a further increase in chemical protection efficiency, the search for more efficient inhibitors and principles of inhibition remain in this direction the main tasks of biophysics.

The study of the excited states of biopolymers, which determine their high chemical activity is advanced. The most successfully was the study of excited states arising at the primary stage of photobiological processes - photosynthesis and vision.

Thus, a solid contribution to an understanding of the primary activation of the molecules of plants of plants is made. The great importance of the transfer (migration) of the energy of excited states without loss from activated pigments to other substrates has been established. A large role in the development of these ideas was played by theoretical works A. N. Terenina (1947 and later). A. A. Krasnovsky (1949) opened and investigated the reaction of the reversible photochemical recovery of chlorophyll and its analogues. Now there is a general conviction that in the near future it will be possible to reproduce photosynthesis in artificial conditions (see also Chapter 5).

Biophysics continue to work on the disclosure of the nature of muscle contraction and mechanisms of nervous excitation and holding (see chapter 11). Study of the transition mechanisms from the excited state to normal is also relevant. The excited state is now considered as the result of a car capatalytic reaction, and braking - as a consequence of a sharp mobilization of inhibitory antioxidant activity as a result of molecular rearrangements in such compounds such as tocopherol (I. I. Ivanov, O. Rolz, 1966; O. R. Kolz, 1970).

The most important common problem of biophysics remains the knowledge of the qualitative physicochemical features of living matter. Such properties as the ability of living biopolymers selectively bind potassium or polarize the electric current, it is not possible to preserve even with their most careful removal from the body. Therefore, cell biophysics continues to intensively develop criteria and methods for a lifetime study of living matter.

Despite the youth of molecular biology, the successes achieved by it in this area are truly overwhelming. For a relatively short period, the nature of the gene and the basic principles of its organization, reproduction and operation are established. Moreover, not only the reproduction of in vitro genes was carried out, but also for the first time a full synthesis of the gene itself was completed. The genetic code has been fully deciphered and the most important biological problem of protein biosynthesis specificity is allowed. The main paths and mechanisms for the formation of protein in the cell were identified and investigated. The primary structure of many transport RNA - specific adapter molecules, carrying out the translation of the nucleic matrices into the amino acid sequence of the synthesized protein, is fully determined. The amino acid sequence of many proteins is fully decrypted and the spatial structure of some of them is installed. This made it possible to find out the principle and details of the functioning of enzyme molecules. The chemical synthesis of one of the enzymes is ribonuclease. The basic principles of the organization of different sub-cell particles, many viruses and phages and solved the main ways of their biogenesis in the cell are established. Open approaches to understanding ways to regulate the activity of genes and clarifying the regulatory mechanisms of vital activity. Already a simple list of these discoveries suggests that the second half of the XX century. was marked by the huge progress of biology, which is obliged first of all in-depth study The structures and functions of biologically essential macromolecules - nucleic acids and proteins.

Achievements of molecular biology are already used in practice today and bring tangible fruits in medicine, agriculture and some industries. There is no doubt that the return of this science will increase every day. However, the main outcome should be considered that under the influence of the success of molecular biology, confidence has strengthened in the existence of unlimited possibilities on the way of disclosing the most intimate secrets of life.

In the future, apparently, new ways of research of the biological form of motion of the Matter will be opened - with molecular level Biology will switch to an atomic level. However, now there is no, perhaps, not a single researcher who could really predict the development of molecular biology even for the next 20 years.