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1、Chapter One: Introduction of Molecular Biology,Definition of Molecular Biology （*）Brief history of Molecular BiologyRelationship between Molecular Biology and other disciplines（*）Prospects of Molecular Biology,Key Points:,1 Definition of Molecular Biology,The attempt to understand the biological phe
2、nomena in molecular terms.The study on the process of DNA replication, transcription, translation and expression regulation and related proteins or enzymes.,The study of gene structure and function at the molecular level.-Robert Weaver,Stage 1: Preparation准备和酝酿阶段Stage 2: Establishing and developing
3、of contemporary Molecular Biology现代分子生物学的建立和发展阶段Stage 3: Primary understanding of the nature of life and modification of life-deep development stage初步认识生命本质并开始改造生命的深入发展阶段Stage 4: Post-genome era后基因组时代,Brief History of Molecular Biology,Molecular biology is a hybrid discipline, it grew out of the dis
4、ciplines of genetics and biochemistry.,From late 1900s to early 1950s (19世纪后期到20世纪50年代初) Confirmed that protein is one of the fundamental materials of life. 确定了蛋白质是生命的主要基础物质 (经典生物化学的贡献) Confirmed that DNA is the nature of genetic material. 确定了生物遗传的物质基础是DNA(经典遗传学的贡献),Stage 1: Preparation,In 1989, Buc
5、hner brothers confirmed that yeast cell-free extracts could make glucose fermentation and produce alcoholIn 1926, J. B. Sumner obtained urokinase crystal from jack bean 从刀豆获得了结晶的尿酶In 1955, F. Sanger sequenced the amino acids of calf insulin 牛胰岛素的氨基酸序列分析Kendrew & peruts obtained the structure of whal
6、e muscle hemoglobin and horse hemoglobin by x-ray diffraction analysis or x-ray crystallography 用X-射线分析得到鲸肌红蛋白与马血红蛋白的空间结构,In 1869, Miescher isolated DNA from used patient badges for the first time and named it nuclein.In 1910, Kossel from Germany isolated the adenine, thymine and histidine 腺嘌呤、胸腺嘧啶和
7、组氨酸。In late 1890, biochemists already knew the components and the structure of RNA,In 1865, Austrian scientists Gregor Mendel published a paper entitled Experiments on Plant Hybrids, and put forward two laws: Principles of Independent Segregation and Independent Assortment;,How Mendels first law (in
8、dependent segregation) explains the 3:1 ratio of dominant to recessive phenotypes among the F2 progeny,The inheritance of flower color in the snapdragon.,How Mendels second law (independent assortment) operates?,In 1900, Hugo de Vries, Carl Correns, Erich von Tschermak rediscovered Mendelian inherit
9、ance law.In 1909, 丹麦geneticists W. Johannsen dubbed “Gene” to substitute Mendels genetic unit.By the end of 1900, chromosome theory of inheritance was put forwarded. In 1910, American scientists Thomas H. Morgan confirmed gene is located on chromosome and discovered genetic recombination phenomenon.
10、,Thomas Hunt Morgan,The inheritance of a sex-linked gene in Drosophila.,The genetic map of chromosome 2 of Drosophila melanogaster.,In 1931, Harriet Creighton & Barbara McClintock found the evidence of gene recombination,Whats the nature of genetic material？,1928, Frederick Griffith: transformation
11、in bacteria: Streptococcus pneumoniae1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty confirmed that, DNA, the transforming material,Conclusion: the genetic material of bacteria is DNA.,In 1952, A.D.Hershey & Martha Chase used labels sulfur-35 (35S) for protein and phosphorus-32(32P) for DNA 。,
12、By definition, the early work on genes cannot be considered molecular biology, or even molecular genetics, because early geneticists did not know the molecular nature of genes. In fact, the chemical composition of genes was not know until 1944. At that point, it became possible to study genes as mol
13、ecules, and the discipline of molecular biology was born.,Conclusion: the genetic material of phage also is DNA.,Stage 2: Establishing and developing of contemporary Molecular Biology,From early 1950s to early 1970s 从50年代初到70年代初 Central Dogma Further understanding on protein structure and function 对
14、蛋白质结构和功能的进一步认识,Discovery of DNA Double Helix DNA双螺旋结构的发现In 1950， Erwin Chargaff rule：A=T；G=CIn 1952，Rosalind Franklin, Maurice Wilkins X-ray picture of B-DNAIn 1953，Pauling published DNA triple helix structureIn 1953，Watson & Crick put forward right-handed double helix model of DNA. They won the Nob
15、el Prize in Physiology and Medicine in 1962 with Wilkins.,DNA double helix,“As a boy, Crick wor- ried that there wouldnt be anything left for him to discover by the time he grew up and became a scientist.”E. Edelson (Francis Crick and James Watson),对DNA 复制的认识,1953年，在发现DNA双螺旋结构同时，Watson和Crick就提出DNA复制
16、的可能模型， 1956年，A. Kornberg首先发现DNA聚合酶； 1958年，Meselson及Stahl用同位素标记和超速离心分离实验为DNA半保留模型提出了证明； 1968年，Okazaki（冈畸）提出DNA不连续复制模型； 1972年，证实了DNA复制开始需要RNA作为引物； 70年代初，获得DNA拓扑异构酶，并对真核DNA聚合酶特性做了分析研究；,对RNA的认识 在研究DNA复制将遗传信息传给子代的同时，提出了RNA在遗传信息传到蛋白质过程中起着中介作用的假说； 1958年，Weiss及Hurwitz等发现依赖于DNA的RNA聚合酶； 1961年，Sydney Brenner,
17、Francis Jacob, Matthew Meselson 发现了 messenger RNA； 1961年，Hall和Spiege-lman用RNA-DNA杂交证明mRNA与DNA序列互补；逐步阐明了RNA转录合成的机理。,对蛋白质的认识 50年代初，Zamecnik等在形态学和分离的亚细胞组分实验中发现微粒体（microsome）是细胞内蛋白质合成的部位； 1957年，Hoagland、Zamecnik及Stephenson等分离出tRNA并对它们在合成蛋白质中转运氨基酸的功能提出了假设； 1961年，Brenner及Gross等观察了在蛋白质合成过程中mRNA与核糖体的结合； 1965年，Holley首次测出了酵母丙氨酸tRNA的一级结构； 60年代，Nirenberg、Ochoa以及Khorana等几组科学家的共同努力破译了RNA上编码合成蛋白质的遗传密码，随后研究表明这套遗传密码在生物界具有通用性，从而认识了蛋白质翻译合成的基本过程。,
