1 《Molecular Biology》双语教学简明教程 第1-4章 安徽师范大学生命科学学院
5 第一章 绪论 Chapter 1 Introduction 【教学目的】 通过本章教学，使学生明确分子生物学的学科性质、基本内容和学习意义，了解本门 课程的教学要求和学习方法。 【重点难点】 明确分子生物学的概念及研究内容。 【教学方法】 多媒体教学 English Animation 【课时安排】 2 课时 主要教学内容 1. Introduction Molecular biology is the study of biology at a molecular level. The field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry. Molecular biology chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interrelationship of DNA, RNA and protein synthesis and learning how these interactions are regulated. The following figure is a schematic that depicts one possible view of the relationship between the fields: Schematic relationship between biochemistry, genetics and molecular biology
6 2. History of Molecular Biology (1) The Early Years of Genetics 1) 1859, Charles Darwin and Evolutionary Theory 2) 1865, Gregor Mendel and Genetics 3) 1869, Discovery of "Nuclein" 4) 1909, Gene, Genotype, Phenotype 5) 1910, Golden Age of Genetics - Thomas Hunt Morgan 6) 1924, it was proposed by Hsien Wu that the protein denaturation is related to its structure. The native protein is folded into a proper structure. But proteins can be denatured through exposure to heat or chemicals. Denatured proteins lose its ordered structure and become loose and disordered. 7) 1941, George Beadle and Edward Tatum: One gene controls one enzyme or one protein. Their work from the 1930s to 1960 marked the transition from classical genetics to the molecular era. 1958, Nobel Prize in Physiology or Medicine. 8) 1943, DNA - Transforming Principle 9) 1952, DNA - Inherited Substance 10) 1953, Unraveling the DNA Double Helix 11) 1967, Cracking the Genetic Code (2) The Birth of Biotechnology 1) 1968, Plasmid 2) 1970, Restriction Enzymes Discovered 3) 1972, Recombinant DNA Technology 4) 1975, DNA Sequencing 5) 1975, Monoclonal Antibody Technology 6) 1978, Human Insulin Cloned 7) 1983, American biologist Kevin M. Ulmer published a paper on Science, and the Protein Engineering was first proposed
7 (3) The Revolution of the Biotechnology 1) 1986, The Polymerase Chain Reaction (PCR) 2) 1987, Victor McKusick and Frank Ruddle added “genomics” to the scientific lexicon as the title for the new journal they cofounded in 1987, with emphasis on linear gene mapping, DNA sequencing, and comparison of genomes from different species. 3) 1989, The Human Genome Project (HGP) 4) 1990, First Case of Gene Therapy 5) 1994, Brave New Foods 6) 1996, Announcing Dolly, First Mammal Cloned from Adult Cells 7) 1996, Development of the Gene Chip 8) 1997, Three Cloned Mice 9) 1997, First Human Artificial Chromosome (4) Welcome to the Genomics and Post-Genomics Era 1) 1998, Race for the Genome 2) 1998, Breakthrough of Stem Cell 3) 1999, Shotgun sequencing 4) 2001, Draft of Human Genome 5) 2001, Cloning Ban 6) 2001-2018, Some cloned animals: cat, pig, horse, dog, monkey. 7) 2006, The Nobel Prize in Physiology or Medicine was awarded jointly to Andrew Fire and Craig C. Mello for their work on RNA interference in C. elegans, which they published in 1998. 8) 2007, The Nobel Prize in Physiology or Medicine was awarded jointly to Mario R. Capecchi, Sir Martin J. Evans and Oliver Smithies "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells". 9) 2008, The Nobel Prize in Physiology or Medicine was awarded jointly to Harald zur Hausen for his discovery of "human papilloma viruses causing cervical cancer" and the other half jointly to Françoise Barré-Sinoussi and Luc Montagnier for their discovery of "human immunodeficiency virus
8 10) 2008, The Nobel Prize in Chemistry was awarded jointly to Osamu Shimomura, Martin Chalfie and Roger Y. Tsien "for the discovery and development of the green fluorescent protein, GFP". 11) 2009, The Nobel Prize in Physiology or Medicine was awarded jointly to Elizabeth H. Blackburn, Carol W. Greider and Jack W. Szostak "for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase". 12) 2009, The Nobel Prize in Chemistry was awarded jointly to Venkatraman Ramakrishnan, Thomas A. Steitz and Ada E. Yonath "for studies of the structure and function of the ribosome". 13) 2010, The Nobel Prize in Physiology or Medicine was awarded to Robert G. Edwards "for the development of in vitro fertilization". 14) 2010, The Nobel Prize in Chemistry was awarded jointly to Richard F. Heck, Ei-ichi Negishi and Akira Suzuki "for palladium-catalyzed cross couplings in organic synthesis". 15) 2011, The Nobel Prize in Physiology or Medicine 2011 was divided, one half jointly to Bruce A. Beutler and Jules A. Hoffmann "for their discoveries concerning the activation of innate immunity" and the other half to Ralph M. Steinman "for his discovery of the dendritic cell and its role in adaptive immunity". 16) 2012, The Nobel Prize in Physiology or Medicine was awarded jointly to Sir John B. Gurdon and Shinya Yamanaka "for the discovery that mature cells can be reprogrammed to become pluripotent" 17) 2012, The Nobel Prize in Chemistry was awarded jointly to Robert J. Lefkowitz and Brian K. Kobilka "for studies of G-protein-coupled receptors" 18) 2013, The Nobel Prize in Physiology or Medicine was awarded jointly to James E. Rothman, Randy W. Schekman and Thomas C. Südhof "for their discoveries of machinery regulating vesicle traffic, a major transport system in our cells". 19) 2014, The Nobel Prize in Physiology or Medicine was awarded jointly to John O’Keefe, May Britt Moser and Edvard Moser "for their discoveries of cells that constitute a positioning system in the brain
9 20) 2015, The Nobel Prize in Physiology or Medicine was awarded jointly to William C. Campbell and Satoshi Ōmura "for their discoveries concerning a novel therapy against infections caused by roundworm parasites" and the other half to Youyou Tu "for her discoveries concerning a novel therapy against Malaria". 21) 2015, The Nobel Prize in Chemistry was awarded jointly to Tomas Lindahl, Paul Modrich and Aziz Sancar “for mechanistic studies of DNA repair”. 22) 2016, The Nobel Prize in Physiology or Medicine was awarded to Yoshinori Ohsumi “for his discoveries of mechanisms for autophagy”. 23) 2017, The Nobel Prize in Physiology or Medicine was awarded jointly to Jeffrey C. Hall, Michael Rosbash and Michael W. Young “for their discoveries of molecular mechanisms controlling the circadian rhythm”. 24) 2017, The Nobel Prize in Chemistry was awarded to Jacques Dubochet, Joachim Frank and Richard Henderson “for developing cryo-electron microscopy for the high-resolution structure determination of biomolecules in solution”. 25) 2018, The Nobel Prize in Physiology or Medicine was awarded jointly to James P. Allison and Tasuku Honjo “for their discovery of cancer therapy by inhibition of negative immune regulation”. 26) 2019, The Nobel Prize in Physiology or Medicine was awarded jointly to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza “for their discoveries of how cells sense and adapt to oxygen availability”. 27) 2020, The Nobel Prize in Chemistry was awarded jointly to Emmanuelle Charpentier and Jennifer A. Doudna “for the development of a method for genome editing”. 28) 2020, The Nobel Prize in Physiology or Medicine was awarded jointly to Harvey J. Alter, Michael Houghton and Charles M. Rice “for the discovery of Hepatitis C virus”. 29) 2021, The Nobel Prize in Physiology or Medicine was awarded jointly to David Julius and Ardem Patapoutian “for their discoveries of receptors for temperature and touch
10 3. What is Molecular Biology? Molecular biology is the study of biology at a molecular level. It chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interrelationship of DNA, RNA and protein synthesis and learning how these interactions are regulated. 4. Contents of Molecular Biology (1) Central dogma (2) Contents of molecular biology ❖ Recombinant DNA Technology ❖ Expression and Regulation of Genes ❖ Structure and Function of Bio-macromolecular ❖ Genome, Transcriptome, Proteome, Bioinformatics 5. Progress and Future of Molecular Biology
11 第二章 基因和染色体 Chapter 2 DNA and Chromosomes 【教学目的】 本章要求学生掌握原核生物和真核生物基因组的区别、染色体的组成、真核生物基因 组的复杂性、DNA 的结构等；掌握 DNA 复制的复杂性、几种 DNA 的复制方式、原核生 物 DNA 复制的酶、真核生物 DNA 复制的酶、DNA 的修复、重组和转座等。 【重点难点】 掌握基本概念、原核生物和真核生物基因组特点、DNA 复制、修复、重组及转座机制。 【教学方法】 讲述式和启发式教学 多媒体教学 English Animation 【课时安排】 10 课时 主要教学内容 Overview Basic material: DNA, RNA, Protein (composition, classes, structures, functions) Transcription: DNA → RNA Transcriptional factors RNA processing: RNA splicing, RNA editing Translation: RNA → Protein Posttranslational modification: Intein splicing, Phosphorylation, Modification. Regulation: Cis-acting elements, Trans-acting factors Central dogma: Old version, New content, Progress. 2.1 DNA and DNA structure 1. Nucleoside & Nucleotide
12 2. Nucleic Acid Chain 3. DNA Structure (1) DNA Primary Structure: nucleotide acid sequence (2) DNA Secondary Structure: double helix Right-handed helix - A-DNA, B-DNA Left-handed - Z-DNA (3) DNA Supercoiling: (4) DNA Denaturation and Renaturation 2.2 Gene and Chromosomes 1. Concepts of Gene (1) Gene - In molecular terms, it is the entire DNA sequence including exons, introns, and noncoding transcription-control regions necessary for production of a functional protein or RNA. In molecular terms, a gene commonly is defined as the entire nucleic acid sequence that is necessary for the synthesis of a functional polypeptide or RNA molecule. (2) Regulatory Gene - A DNA sequence or a gene that functions to control the expression of other genes. (3) Structural Gene - A DNA sequence or a gene that codes the production of RNA, a specific protein or peptide. (4) Gene Cluster - It is a group of adjacent genes that are identical or related. (5) Gene Family - A group of related genes having similar DNA sequence evolved from a single ancester. These genes make similar products and may or may not be located in the same region of a chromosome. 2. Genome (1) Genome - In modern molecular biology the genome of an organism is its total hereditary information encoded in DNA (or, for some viruses, RNA)
13 (2) Genomics – It is a discipline in genetics that applies recombinant DNA, DNA sequencing methods, and bioinformatics to sequence, assemble, and analyze the function and structure of genomes. (3) Structural Genomics - The branch of genomics that attempts to make use of the vast wealth of data produced by genomic projects (such as genome sequencing projects) to describe gene (and protein) functions and interactions. As its name suggests, the aim of structural genomics is to characterize the structure of the genome. Knowledge of the structure of an individual genome can be useful in manipulating genes and DNA segments in that particular species. Structural genomics proceeds through increasing levels of analytic resolution, starting with the assignment of genes and markers to individual chromosomes, then the mapping of these genes and markers within a chromosome, and finally the preparation of a physical map culminating in sequencing. When a number of genomes have been characterized at the structural level, the hope is that, through comparative genomics, it will become possible to deduce the general rules that govern the overall structural organization of all genomes. (4) Functional Genomics – It is a field of molecular biology that attempts to make use of the vast wealth of data produced by genomic projects (such as genome sequencing projects) to describe gene (and protein) functions and interactions. Unlike genomics, functional genomics focuses on the dynamic aspects such as gene transcription, translation, and protein–protein interactions, as opposed to the static aspects of the genomic information such as DNA sequence or structures. Functional genomics attempts to answer questions about the function of DNA at the levels of genes, RNA transcripts, and protein products. A key characteristic of functional genomics studies is their genome-wide approach to these questions, generally involving high-throughput methods rather than a more traditional “gene-by-gene” approach. 3. Size of Genome (1) Prokaryotic cell vs Eukaryotic cell (2) Relationship of genomic size and evolution