In 187 1, Lankester proposed that it is more important to find and analyze the chemical and molecular differences between different species of organisms than to compare the overall morphology when determining the phylogenetic relationship. Later, physiological and chemical laboratories in Germany and the United States
The establishment of Journal of Biochemistry promoted the development of biochemistry. When biochemistry deeply studies biological macromolecules,
1938, Weaver first used the word molecular biology in his report to Rockefeller Foundation. "Among the research supported by the Foundation, there are a series of relatively new fields, which can be called molecular biology …" he wrote. A year later, Astbury, who studied the structure of protein, used this term, and it became more and more common. Especially in 1953, after Watson and Crick published the famous paper "The Structure of Deoxyribonucleic Acid", the discovery of DNA double helix structure promoted the combination of genetics, biochemistry and biophysics, promoted the formation and rapid development of molecular biology, and made life science enter the era of molecular level research in an all-round way, which was a major milestone in the history of biological science development. 1956, Cambridge Medical Research Council took the lead in establishing a molecular biology laboratory, 1959, the journal of molecular biology was founded, and 1963, the international organization of European molecular biology was established. As a result, molecular biology has become a brand-new independent discipline, which has promoted the rapid development of life science and become an important field of modern natural science research.
In the process of the formation and development of molecular biology, there are many important discoveries and events, as follows:
1864: Hooper-Seiler crystallized and named hemoglobin.
1869: Mieseher isolated DNA for the first time.
187 1 year: Lankester proposed for the first time to discover and analyze the chemical and molecular differences among different species of organisms, and determined the system.
The relationship between unity and occurrence is more important than the comparative study of the overall form.
1926: Sumaer obtained urease crystals from the extract of concanavalia, which proved that this protein crystal had catalytic activity. In the same year, Swedberg established the first ultra-high speed centrifuge for analysis, and used it to determine the relative molecular weight of hemoglobin about 6.8X 104.
193 1 year: Pauling published the first paper on the characteristics of chemical bonds, explaining the valence bonds of * * * in detail.
Regularity. Later, the quantum mechanics theory of dealing with biomolecules was established.
1934: Bernal and Crowfoot published the first detailed X-ray diffraction pattern of pepsin crystal.
194 1 year: Astbury obtained the first X-ray diffraction pattern of DNA.
1944: The evidence provided by Avery shows that it is DNA, not protein, that carries the genetic information during the transformation of bacteria. Experiments have proved that DNA is the basic element to transform nontoxic R-pneumococcus into pathogenic S-pneumococcus. Eight years later, 1952, Hershey and Chase proved that T2 phage infected Escherichia coli, mainly nucleic acid entered the bacteria, while virus coat protein remained outside the cell. The reconstruction experiment of tobacco mosaic virus shows that the characteristics of virus protein are determined by RNA, that is, the genetic material is nucleic acid rather than protein. At this point, DNA is generally accepted as a genetic material.
1950: Chargaff overthrew the tetranucleotide theory with accurate data of DNA base composition from different sources, and put forward Chargaff's rule, that is, the base composition of DNA has the same law, the molar content of thymine is always equal to adenine, and the molar content of cytosine is always equal to guanine, that is, [a] = [t], [g] = [c].
195 1 year: Pauling and Corey applied X-ray diffraction crystallography theory to study the fine spatial structure of amino acids and peptides, and put forward two periodic polypeptide structure theories, namely α helix theory and B folding theory.
1953: This is the first year to open a new era of life science. The landmark is that Watson and Crick published the famous paper "The Structure of Deoxyribonucleic Acid". Based on the research results of Franklin and Wilkins' X-ray diffraction, they deduced the model of DNA double helix structure, which opened a new era of biological science. In the same year, after eight years of research, Sanger completed the first protein-the amino acid sequence analysis of insulin.
Subsequently, Gamnow studied the coding law of genetic code in theory in 1954. 1956, Volkin and Astrachan discovered mRNA (this name was not used at that time); 1958, Hoagland and others discovered the role of tRNA in the synthesis of protein. Meselson and Starr used isotopes and ultracentrifugation to prove semi-conservative replication of DNA. Crick put forward the central rule of genetic information transmission.
1960: Marmur and Dory discovered the renaturation of DNA, which confirmed the specificity and reliability of nucleic acid hybridization reaction; Rich proved that DNA-RNA hybrid molecules are related to information transmission between nucleic acids, which initiated the practical application of nucleic acids. Meanwhile, in the study of protein structure, Kendrew et al. obtained the myoglobin structure with a resolution of 0.2nm, and Perutz et al. obtained the hemoglobin structure with a resolution of 0.55nm.
196 1 year: This is an extraordinary year for the development of molecular biology. Jacob and Monod put forward the operon theory and published a paper on the genetic regulation mechanism in protein synthesis, which is regarded as one of the classic papers in molecular biology. In the same year, brenner and others obtained the evidence of mRNA; Hall and Pigman proved that T2 DNA and T2-specific RNA are complementary in sequence. Crick and others proved the universality of genetic code.
1962: Arber put forward the first evidence to prove the existence of restriction enzymes, which led to the purification of such enzymes in the future.
Nathans and Smith applied it to DNA mapping and sequence analysis.
1965: Holley et al. determined the primary structure of yeast alanyl -tRNA by overlapping method for the first time, which laid a foundation for extensive and in-depth study of the advanced structure of tRNA.
1967: Gellert discovered DNA ligase, which connects DNA fragments with the same sticky end or blunt end. In the same year, Philips and his colleagues determined the three-dimensional structure of lysozyme with a resolution of 0.2 nm.
1970: Reverse transcriptase was discovered almost simultaneously in Teming and Baltimore, which confirmed the "pre-"proposed by Teming 1964.
Virus hypothesis ". After infection with Lauder's sarcoma virus (RSV), the first pre-DNA virus containing all the genetic information of RNA virus genome was produced, and the RNA of the offspring virus was synthesized by using the DNA of the former virus as a template. Reverse transcriptase has become an important tool in molecular biology research.
1972 ~ 1973: the era of recombinant DNA has come. Berg, Boyer and Cohen created DNA cloning technology, constructed bacterial plasmids with biological functions in vitro, and initiated a new era of genetic engineering. At the same time, Singh and Liang Junnuo proposed a liquid mosaic model of biofilm structure.
1975: Southern invented the imprinting method for separating DNA fragments by gel electrophoresis; Gruustein and Hogness established a new method to clone specific genes; O 'Farrell invented the method of analyzing protein by two-dimensional electrophoresis, which created important technical conditions for the further development of molecular biology. Blobel et al. reported signal peptides.
1976: Bishop and Varmus found that the oncogene of animal tumor virus comes from cell gene (i.e. protooncogene).
1977: Berget and others discovered the "broken" gene; Sanger, maxam and Gilbert founded the "enzymatic method" and "chemical method" to determine DNA sequence, which marked the arrival of a new era of molecular biology research.
1979: Solomon and Bodmer first proposed that at least 200 restriction fragment length polymorphisms (RFLP) can be used as the basis for connecting the whole human genome map.
1980: Wigler et al. introduced non-selective genes into mammalian cells by infecting selective markers * * *; Cohen and Boyer obtained the patent of American cloning technology.
198 1 year: Cech et al. discovered the self-splicing effect of the precursor of Tetrahymena 26S rRNA, and later proved that the insertion sequence (IVS) in the precursor has five enzyme activities. Almost at the same time, Altman proved from the purified RNase P that RNA in RNase P is the catalyst for the maturation of t RNA precursors. The discovery of catalytic RNA (ribozyme) promoted the rapid development of RNA research.
1982: Prusiner and others found prions in the brains of hamsters infected with pruritus.
1983: Herrera-Estrella and others successfully transformed plant cells with Ti plasmid as transgenic vector.
1984: McGinnis et al. found homeobox genes such as Drosophila and Xenopus laevis.
Nucleotide sequence; Schwartz and Cantor invented pulsed gradient gel electrophoresis; Simons and Kleckner discovered antisense RNA.
1985: Saiki and others invented polymerase chain reaction (PCR); Sinsheimer first proposed the human genome mapping system.
Make plans; Smith et al. reported the method of replacing isotope labeling with fluorescent labeling in DNA sequencing; Miller et al. discovered the zinc finger structure of DNA binding protein.
1986: Dryja found that retinoblastoma (Rb) gene is a tumor suppressor gene; Robin et al. confirmed the helix structure of DNA binding protein by X-ray crystallography.
1987: Milkin and others found that triple-stranded DNA was in the acidic solution of plasmid; Burke and others cloned a large section of DNA with yeast artificial chromosome (YAC) as the vector. Hoffman et al. confirmed that the protein product of muscle atrophy focus of Dnchenne was dystrophinHooper et al. and Kuehn et al. respectively made great progress in transgenic operation of mammalian embryos with embryonic base cells.
1988: Landsehalz et al. discovered the periodicity of leucine sequence in the binding region during the study of CyC3 (cytochrome c gene regulatory protein), oncogene products (MyC, V-jun, V-fos) and CBP(CCAAT box binding protein), and proposed a leucine zipper structure model of DNA binding protein; In the same year, Whyfe and others proved that the occurrence of cancer is the result of activation of oncogenes and inactivation of tumor suppressor genes.
1989: Greider et al. first discovered that telomerase is a reverse transcriptase with endogenous RNA as the template in ciliated protozoa; Hiatt et al reported for the first time that monoclonal antibodies can also be produced in plants.
1990: The Human Genome Project (HGP) was officially launched; Simpson et al. discovered a small molecule RNA (guiding RNA) which can guide the editing of mRNA precursors. Sinclair et al. found a new sex-determining gene-SRY gene on human Y chromosome.
199 1 year: 147 scientists from 35 laboratories in 17 countries were organized by European homologous (EC) organizations, and the first complete chromosome (yeast chromosome 3) was manually sequenced. Hake et al. reported for the first time that genes containing homeoboxes were found in plants. Blackburn et al. proposed that the general formula of single-stranded DNA for regulating polymerization sequence is (T/A)mGn, m = 124, n = 1 ~ 8], which can form an intramolecular or intermolecular quadruplex structure and play a role in stabilizing chromosomes.
1993: Jurnak and others discovered a new protein structure-parallel B helix); When studying pectate lyase; Yuan et al. discovered a protein -IL- 1B converting enzyme (ICE) which is involved in regulating apoptosis and has shearing function in mammalian cells.
1994: Japanese scientists publish rice genome genetic map in (natural genetics); Wilson waited for three years.
The continuous determination of 2.2Mb on chromosome 3 of C. elegans was completed in time, marking the arrival of the era of DNA sequencing with a scale of one million bases.
1995: Cuenoud and others discovered that DNA has enzymatic activity; Tu et al. found RNA- 10 Sa RNA with dual functions of transport and messenger in Escherichia coli.
1996: Lee et al reported for the first time that the amino acid fragment in yeast transcription factor GCN4 can automatically catalyze the synthesis of self-replicating peptides; Hong Guofan and others used the "fingerprint-anchor" strategy to construct a high-resolution physical map of rice genome, and the length of DNA fragment was120 kb. . Goffeau et al. completed the complete sequence determination of yeast genomic DNA (1.25X 10 7bp).
1997: Wilmut and others successfully obtained cloned sheep-Dolly); It is the first time to use the genetic material of adult ewe somatic cells without fertilization; Willard et al. constructed human chromosome (HACS) for the first time; Salishury et al. discovered a new form of DNA structure-four dominant combinations, which may be a way of DNA connection during gene exchange.
1998: renard et al. obtained a cloned cow-Margerive through somatic cell operation, which proved once again that mammals with identical genes can be cloned from somatic cells; GeneBank has published the latest human "Gene Map 98'", which represents the location information of 30 18 1 gene. Venter put forward a new strategy of human genome project-whole genome random sequencing, and capillary electrophoresis sequencer began to work.
From the development of molecular biology mentioned above, it can be seen that the 20th century focused on the research of nucleic acids, which promoted the in-depth development of molecular biology. The double helix structure in the 1950s, the operon theory in the 1960s, DNA recombination in the 1970s, PCR technology in the 1980s and DNA sequencing in the 1990s all have milestone significance, bringing life science into an era from macro to micro and from analysis to synthesis.