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How did molecular biology come into being and develop? What are the important stages? What are the main figures and achievements?
The science of studying life phenomena at the molecular level. By studying the structure, function and biosynthesis of biological macromolecules (nucleic acid, protein), the essence of various life phenomena is clarified. The research content includes various life processes. Such as photosynthesis, the molecular mechanism of development, the mechanism of neural activity, and the occurrence of cancer. Molecular biology is a science that studies the structure and function of biological macromolecules at the molecular level to clarify the nature of life phenomena. Since 1950s, molecular biology has been the frontier and growing point of biology, and its main research fields include protein system, protein-nucleic acid system (centered on molecular genetics) and protein-lipid system (i.e. biofilm). The study on the structure and function of biological macromolecules, especially protein and nucleic acid, is the basis of molecular biology. The application of modern chemical and physical theories, techniques and methods in molecular biology has promoted the research on the structure and function of biological macromolecules, which has led to the vigorous development of molecular biology in the past 30 years. Molecular biology is closely related to biochemistry and biophysics. The main differences between them are as follows: ① Biochemistry and biophysics use chemical and physical methods to study biological problems at different levels, such as molecular level, cell level, whole level and even group level. Molecular biology focuses on studying the universal laws of life activities at the molecular level (including multi-molecular systems); ② At the molecular level, molecular biology focuses on macromolecules, mainly protein, nucleic acids, lipid systems and some polysaccharides and their complex systems. The transformation of some small molecular substances in organisms belongs to the category of biochemistry; The main purpose of molecular biology research is to clarify the basic characteristics shared by the whole biological community at the molecular level, that is, the essence of life phenomena; The study of physical and chemical phenomena or changes of a specific organism or a specific organ in an organism belongs to biophysics or biochemistry.

[Edit this paragraph] A brief history of development

Structural analysis and genetic material research have made important contributions to the development of molecular biology. The central content of structural analysis is to explain the physiological function of cells by clarifying the three-dimensional structure of biomolecules. 19 12 years, the British W. H. Prague and W. L. Prague established X-ray crystallography, and successfully determined the structures of some rather complicated molecules and protein. Later, Prague students W T Astbury and J D Bernard made a preliminary structural analysis of fibrin such as hair and muscle, pepsin and tobacco mosaic virus. Their work laid the foundation for the formation and development of biomacromolecule crystallography. In 1950s, molecular biology emerged and developed rapidly as an independent branch discipline. Firstly, in the aspect of protein structure analysis, 195 1 year, L.C. Pauline and others proposed the α-helix structure, and described a conformation of peptide chain in protein molecule. Sanger completed the determination of the amino acid sequence of insulin. Then J.C. Chendru and M.F. Peroots used heavy atom isomorphic replacement technology and computer technology in X-ray analysis, and expounded the three-dimensional structures of myoglobin of whale and hemoglobin of horse in 1957 and 1959 respectively. 1965, Chinese scientists synthesized insulin with biological activity, which was the first time that protein synthesized it artificially. On the other hand, M. delbruck's team chose phage from 1938 and began to explore the mystery of genes. Hundreds of identical progeny phage particles are replicated within half an hour after phage infects the host, which is an ideal material for graduate students to replicate themselves. 1940, G.W. Bedell and E.L. Tatum put forward the hypothesis of "one gene, one enzyme", that is, the function of a gene is to determine the structure of an enzyme, and a gene only determines the structure of an enzyme. But at that time, the nature of genes was not clear. 1944, O.T. Avery studied the phenomenon of protein engineering transformation in bacteria and proved that DNA is genetic material. 1953, J.D. Watson and F.H. Crick put forward the double helix structure of DNA, which initiated a new era of molecular biology. On this basis, the central rule is put forward, which describes the flow of genetic information from gene to protein structure. The elucidation of genetic code reveals the storage mode of genetic information in organisms. 196 1 year, F. Jacob and J. Mono put forward the concept of operon and explained the regulation of gene expression in prokaryotes. By the mid-1960s, the general nature of DNA self-replication and transcription into RNA was basically clear, and the mystery of genes began to be solved. In a short period of about 30 years, molecular biology has moved from bold scientific assumptions to a large number of experimental studies, thus laying the theoretical foundation for this discipline. In 1970s, due to the breakthrough of recombinant DNA research, genetic engineering blossomed in practical application, and the protein project to transform the structure of protein also became a reality.

[Edit this paragraph] Basic content

The structural unit of protein system protein is α-amino acid. There are 20 common amino acids. They are arranged in different order, providing astronomical figures for the life world. The molecular structure of protein can be divided into four main levels. Primary structure, also called chemical structure, is the arrangement order of amino acids in molecules. The end-to-end amino acids form a chain structure through the condensation of amino groups and carboxyl groups, which is called peptide chain. The local spatial arrangement of the main chain atoms of peptide chain is secondary structure. The secondary structure is curled into a tertiary structure in space. Some protein molecules are assembled from the same or different subunits, and the relationship between subunits is called quaternary structure. The special properties and physiological functions of protein are closely related to the specific structure of its molecules, which is the molecular basis of various colorful life activities in protein. Studying the relationship between structure and function of protein is an important content of molecular biology research. With the development of structural analysis technology, thousands of chemical structures of protein and hundreds of three-dimensional structures of protein have been clarified. Since the late 1970s, the method of inferring the chemical structure of protein by determining complementary DNA sequences has not only improved the analysis efficiency, but also made it possible to analyze the chemical structure of protein, which is difficult to meet the requirements of amino acid sequence analysis. Finding and identifying protein with new functions is still the content of protein's research. For example, protein's research on gene regulation and higher nervous activity has attracted much attention. The genetic characteristics of protein-nucleic acid system organisms are mainly determined by nucleic acids. The genes of most organisms are composed of DNA. The genome of a simple virus such as λ phage is a double-stranded DNA consisting of 46,000 nucleotides in a certain order (because it is a double-stranded DNA, its length is usually calculated in base pairs). The genome of bacteria, such as E.coli, contains 4× 106 base pairs. The DNA contained in human cell chromosomes is 3× 109 base pairs. Genetic information needs to be copied, transcribed and translated in the life activities of future generations. Replication is the synthesis of offspring DNA molecules using parent DNA as a template. Transcription determines the nucleotide sequence of a class of RNA molecules according to the nucleotide sequence of DNA; The latter further determines the sequence of amino acids in protein molecule, which is translation. Because this RNA plays a role in information transmission, it is called messenger ribonucleic acid (mRNA). Because there are four kinds of nucleotides that make up RNA, but there are 20 kinds of amino acids in protein, their corresponding relationship is that an amino acid is determined by three nucleotides connected in a certain order in the mRNA molecule, which is the triplet genetic code. In the process of expressing its traits, genes run through the interaction between nucleic acid and protein. In DNA replication, the double-stranded helix is dismantled under the action of helicase, and then DNA polymerase copies the offspring DNA chain with the parent DNA chain as the template. Transcription is accomplished under the catalysis of RNA polymerase. The translation site ribonucleoprotein is a complex of nucleic acid and protein. According to the encoding of mRNA, amino acids are linked into a complete peptide chain under the catalysis of enzymes. The regulation of gene expression is also achieved through the interaction of biological macromolecules. For example, the manipulation gene on the lactose operon of Escherichia coli controls the gene switch by interacting with the repressor protein. Non-histones in eukaryotic chromatin play a special role in transcription regulation. Under normal circumstances, only 2 ~ 15% genes are expressed in eukaryotic cells. This selective transcription and translation is the basis of cell differentiation. Protein-lipid system is a ubiquitous membrane structure in organisms, collectively referred to as biofilm. It includes cell peripheral membrane and organelle membrane with various specific functions in cells. From the chemical composition, biofilm is a system composed of lipid and protein through non-covalent bonds. Many membranes also contain a small amount of sugar in the form of glycoproteins or glycolipids. The fluid mosaic model proposed by 1972 summarizes the basic characteristics of biofilm: its basic skeleton is lipid bilayer structure. Membrane proteins can be divided into those expressed in protein and those embedded in protein. Membrane lipids and membrane proteins are constantly moving. Biofilm has bilateral asymmetry in structure and function. Take the transportation of materials as an example. Some substances can pass through the membrane at high speed, while others cannot. Like kelp, it can concentrate 30,000 times of iodine from seawater. Selection of biofilm The permeability of fluid mosaic model of biofilm makes the pH and ion composition in cells relatively stable, maintains the ion gradient necessary for nerve and muscle excitement, and ensures the function of cell to concentrate nutrition and eliminate waste. Biological energy conversion is mainly carried out on the membrane. The way organisms get energy, or use solar energy to carry out photosynthetic phosphorylation on chloroplast membrane like plants; Or oxidative phosphorylation of mitochondrial membrane with food like animals. Although their energy sources are different, their basic processes are very similar, and finally adenosine triphosphate is synthesized. For these two energy conversion mechanisms, P. Mitchell's chemical permeation theory has gained more and more evidence. The efficiency of food oxidation to release energy can reach about 70%, while the efficiency of coal or oil combustion to obtain energy is usually 20 ~ 40%, so the study of biomechanics is highly valued. A deep understanding and simulation of energy conversion of biofilm will help human beings to use energy more effectively. Another important function of biofilm is information transmission between cells or inside and outside the cell membrane. On the cell surface, there is a kind of protein widely called receptor. The effects of hormones and drugs need to be realized by specific binding with receptor molecules. The distribution of receptor substances on the surface of cancer cells has changed obviously. The surface properties of cell membrane also play an important role in regulating cell division and reproduction. The study of cell surface properties led to the study of sugar. More and more attention has been paid to the study of the structure and function of biological macromolecules such as glycoprotein, proteoglycan and glycolipid. From the development trend, the system formed by oligosaccharide and protein or lipid will become a new important field of molecular biology research.

[Edit this paragraph] Theoretical significance and application

The achievements of molecular biology show that the basic laws of life activities are unified in all kinds of organisms. For example, protein and nucleic acid are composed of the same amino acids and nucleotides in any organism. Genetic material, except some viruses, is DNA, which replicates in all cells through the same biochemical mechanism. With a few exceptions, the central principles and genetic codes of molecular genetics are universal in most cases. The achievement of physics proves that all the atoms of matter are composed of a few elementary particles according to the same law, which shows that the structure of the material world is highly consistent and reveals the essence of the material world, thus promoting the development of the whole physics discipline. Molecular biology reveals the high consistency between the basic structure of the life world and the fundamental laws of life activities at the molecular level, and reveals the essence of life phenomena. Just as the study of elementary particles in the past led to the development of physics, the concepts and viewpoints of molecular biology have penetrated into every branch of basic biology and applied biology, thus leading to the development of the whole biology and raising it to a new level. In the past, the study of biological evolution mainly relied on the morphological and anatomical comparison between different species to determine the genetic relationship. With the development of protein and nucleic acid structure determination methods, by comparing the chemical structures of protein or nucleic acids of different species, we can judge their genetic relationship according to the degree of difference. The phylogenetic tree obtained in this way is basically consistent with that obtained by classical methods. It has unique advantages to study classification and evolution by molecular biology methods. First of all, the structure of basic biological macromolecules that constitute organisms reflects more essential aspects of life activities. Secondly, according to the degree of structural differences, we can give a quantitative and thus more accurate concept of kinship. Thirdly, for the evolution of microorganisms with very simple morphological structure, only in this way can we get reliable results. Higher nervous activity of higher animals is an extremely complicated life phenomenon. In the past, research was mostly carried out at the cellular level or even at the overall level. In recent years, the results of in-depth research at the molecular level fully show that higher nervous activity is also based on the activities of biological macromolecules. For example, in the process of learning and memory in higher animals, the composition of RNA and protein in the brain will change obviously, and some drugs that affect the synthesis of protein in organisms will also significantly affect the ability of learning and memory. For another example, "biological clock" is a well-known biological phenomenon. Experiments with chickens show that an important neurotransmitter (5- hydroxytryptamine), a hormone (melatonin) and an enzyme control their changes, and their contents in chicken brains change periodically for 24 hours. It is this change that constitutes the material basis of chicken's "biological clock". In application, clarifying the energy conversion principle of biofilm will help solve the global energy problem. Understanding the catalytic principle of enzymes can make artificial simulated enzymes more targeted and design new catalysts widely used in chemical industry, thus bringing a revolution to the chemical industry. Molecular biology of genetic engineering has also played a great role in bioengineering technology. The success of 1973 recombinant DNA technology paved the way for the development of genetic engineering. Since 1980s, some genes from higher animals have been introduced into single-celled organisms by genetic engineering technology to produce interferon, polypeptide hormones and vaccines by fermentation. The further development of genetic engineering will provide a fundamental solution for directionally cultivating excellent varieties of animals, plants and microorganisms and effectively controlling and treating some genetic diseases of human beings. A lot of progress has been made in the study of cell carcinogenesis from the perspective of gene regulation. Molecular biology will make an important contribution to the ultimate conquest of cancer.

[Edit this paragraph] Application of molecular biology

1, paternity test In recent years, the progress of human genome research is changing with each passing day, and molecular biology technology is also improving. With the continuous penetration of genome research into various disciplines, the progress of these disciplines has reached an unprecedented height. In forensic medicine, the detection of STR loci and SNP loci is the core of the second and third generation DNA analysis technologies respectively, and it is a detection technology developed after the research of RFLPs (Restrictive Fragment Length Polymorphism) VNTRs (Variable Number Tandem Repeat Sequence Polymorphism). As the most advanced biotechnology of megabace dna analysis system, dna analysis provides a scientific, reliable and rapid means for forensic material evidence examination, which makes the identification of material evidence transition from individual exclusion to the same level of identification. DNA testing can directly identify crimes and provide accurate and reliable basis for solving major and difficult cases such as murder, rape and murder, dismemberment and pregnancy caused by rape. With the development and application of DNA technology, the detection of DNA labeling system will become an important means and way to solve the case. As a paternity test, this method is very mature and internationally recognized as the best method. 2. As a comprehensive science of modern science, molecular biology is more meaningful than pure scientific value; More importantly, its development is related to all aspects of human beings. Molecular biology can be divided into macromolecular biology and electronic biology. The above-mentioned applications in criminal investigation, including but not limited to personal identification and baby sex identification, are generally the practical application of macromolecular content. Electronic biology, on the other hand, explains the basic elements and composition of life from the perspective of small molecules and atoms that are more detailed than macromolecules, with more unsolved mysteries and broader scientific prospects. At present, cloning technology is basically only an application in the primary stage of this subject. As you can imagine, with the deepening of research and the further development of physics in the future. Humans may become "gods" who create other creatures.