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第一章分子生物学的发展历史郑伟娟2006WhatisMolecularbiology?1.1.分子生物学的概念Thetermhasmorethanonedefinition.Defineinbroadly：understandbiologicalphenomenainmolecularterms(difficulttodistinguishfrombiochemistry)Defineinrestrictively：thestudyofgenestructureandtheiractivitiesinmolecularlevelWhatisMolecularbiology?遗传学（genetics）生物化学（biochemistry）分子生物学（molecularbiology）1.2.分子生物学发展简史TransmissionGenetics传递遗传学In1865,GregorMendelpublishedMendelianinheritance(孟德尔遗传定律).gardenpeaInheritanceoccurredthroughblendingofeachtraitoftheparentsintheoffspring.Inheritanceisparticulate（微粒，微粒的）.Eachparentcontributesparticles,orgeneticunits,totheoffspring.1822-1884（遗传）,demonstratedthatgenesareonthechromosomefruitfly(Drosophiamelanogaster)1866-1945://!FrederickGriffith肺炎球菌转化试验1877-1955（尿黑酸症）GeorgeBeadleandE.L.Tatum,Neurospora（脉孢菌属/链孢菌属）one-gene/one-enzymehypothesisMostgenescontaintheinformationformakingonepolypeptide.TheoverallstructureofDNA1951JamesWatson(23y)丹麦哥本哈根剑桥大学CavendishLab.FrancisCrick(35y)1953,doublehelixMolecularStructureofNucleicAcids:AStructureforDeoxyriboseNucleicAcid(Nature,April25,1953.volume171:737-738.)RosalindFrankinX~rayphotographofDNAwithhighquality(核与磷酸连接成的扭曲绳子，每一节上都有配对的碱基)1951.King’sLab.LondonUniversityUKM.H.F.WilkinsJamesWatson(34y)FrancisCrick(46y)MauriceWilkins(46y)1962NobelPrize1958，MatthewMeselsonandFranklinStahlprovedthatDNAreplicationinbacteriafollowsthesemiconservativepathway.MatthewMeselsonandFranklinStahlmorerecentlyFacultymemberatHarvardMechanismsofMolecularEvolutionFacultyChairforCBWStudiesFacultymemberatU.ofOregonMeioticRecombinationFrancoisJacobandSydneyBrennerTheribosomesarenonspecifictranslationmachinesthatcanmakedifferentproteins,accordingtotheinstructionsinthemRNAsthatvisittheribosomes.Intheearly1960sMarshallNirenbergGobindKhoranaRobertW.Holleyfortheirinterpretationofthegeneticcodeanditsfunctioninproteinsynthesis.1968NobelPrizeinMedicine1927-1922-1922-onegeneonepolypeptidenormalgenenormalfunctionmutantgenegeneticdisorderTechnique:genecloning1975.HowardTemin(41y)DavidBaltimore(37y)Reversetranscription（引发癌症的内因）TheNobelPrizeinChemistry1980fortheircontributionsconcerningthedeterminationofbasesequencesinnucleicacidsWalterGilbertFrederickSanger1932-1918-forhisworkonthestructureofproteins,especiallythatofinsulinTheNobelPrizeinChemistry1958FrederickSanger1918-1983.BarbaraMcClintock(86y)DNAtransposableelementTheNobelPrizeinChemistry1989fortheirdiscoveryofcatalyticpropertiesofRNARibozymeSidneyAltmanThomasR.CechYaleUniversityNewHaven,CT,USAUniversityofColoradoBoulder,CO,USA1939-1947-TheNobelPrizeinChemistry1993KaryB.Mullis1944-forhisinventionofthepolymerasechainreaction(PCR)methodEdwardB.LewisChristianeNüsslein-VolhardEricF.WieschausTheNobelPrizeinPhysiologyorMedicine,1995discoveredGeneticcontrolofearlydevelopmentinDrosophila（果蝇）In1997,lanWilmutandcolleaguesclonedasheep(Dolly)fromanadultsheepuddercell.1997，TheNobelPrizeinPhysiologyorMedicineforhisdiscoveryofPrions–anewbiologicalprincipleofinfectionStanleyB.PrusinerUniv.ofCalifornia,SchoolofMedicineUSA1942-discoveredkeyregulatorsofthecellcycleLelandH.HartwellR.Timothy(Tim)HuntSirPaulM.NurseTheNobelPrizeinPhysiologyorMedicine20012002NobelPrizeJohnSulstonSydneyBrennerH.RobertHorvitzProgrammedCellDeath(PCD)anddevelopment1.3.分子生物学的研究概况还原论20世纪人类对生命现象的认识个体染色体基因DNAdNt基因的概念基因的本质基因的功能逐步深刻认识人类对生命现象的认识还原论20世纪生命科学的飞跃了解整个生命现象的本质仍然是零敲碎打研究策略（piecemeal）人类对生命现象的认识整体论揭示生命的奥秘21世纪GenomicsStructuralGenomicsFunctionalgenomics数、理、化相关学科生物学实验技术渗透交叉近代生物学生物学个性共性宏观生物学（生态学为核心）微观生物学（分子生物学为核心）细胞水平分子水平结构生物学，发育生物学，神经生物学等新兴学科发展生物多样性研究资源保护与利用人类生态环境的保护工农业生产持续发展分子生物学在现代生物学中的地位分子生物学分子结构生物学分子发育生物学分子神经生物学分子育种学分子肿瘤学分子细胞生物学分子免疫学分子病毒学分子生理学分子考古学分子遗传学分子数量遗传学分子生态学分子进化学…………….分子生物学的延伸分子生物学已经渗透到生物学的几乎所有领域分子生物学已经成为生命科学领域的带头学科21世纪生命科学发展的特点•对生命现象的认识从单基因水平向全基因组整体水平发展•现代生命科学研究的理论与技术从较长期的积累走向应用