分子生物学的发展历史.学习资料

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/RC/AB/BC/Gregor_Mendel.htmlIn1910,ThomasHuntMorganprovidedthefirstdefinitiveevidenceforthe

Chromosometheoryofinheritance

fruitfly(Drosophiamelanogaster)

1866-1945/medicine/laureates/1933/morgan-bio.htmlMolecularGeneticsWhatgenesaremadeofandhowtheywork?ThediscoveryofDNA1869,FriedrichMiescher

discoverednucleinandthemajorcomponentofnucleinisDNA.1844-1895http://www.fmi.ch/members/marilyn.vaccaro/ewww/index2.htmlTheCompositionofGenesFrederickGriffith肺炎球菌转化试验1877-1955/dnaftb/concept_17/con17bio.htmlHowdoesgeneswork?1902,ArchibaldGarrod,alcaptonuria（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,doublehelix"MolecularStructureofNucleicAcids:

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.Holley

fortheirinterpretationofthegeneticcodeanditsfunctioninproteinsynthesis.1968NobelPrizeinMedicine1927-1922-1922-onegeneonepolypeptidenormalgenenormalfunctionmutantgenegeneticdisorderTechnique:genecloning

HowardTemin(41y)DavidBaltimore(37y)Reversetranscription（引发癌症的内因）TheNobelPrizeinChemistry1980"fortheircontributionsconcerningthedeterminationofbasesequencesinnucleicacids"WalterGilbert

FrederickSanger

1932-1918-"forhisworkonthestructureofproteins,especiallythatofinsulin"TheNobelPrizeinChemistry1958FrederickSanger

1918-1983.BarbaraMcClintock(86y)DNAtransposableelementTheNobelPrizeinChemistry1989"fortheirdiscoveryofcatalyticpropertiesofRNARibozyme"SidneyAltman

ThomasR.CechYaleUniversity

NewHaven,CT,USAUniversityofColorado

Boulder,CO,USA1939-1947-TheNobelPrizeinChemistry1993KaryB.Mullis

1944-"forhisinventionofthepolymerasechainreaction(PCR)method"EdwardB.LewisChristianeNüsslein-Volhard

EricF.WieschausTheNobelPrizeinPhysiologyorMedicine,1995discoveredGeneticcontrolofearlydevelopmentinDrosophila（果蝇）In1997,lanWilmutandcolleaguesclonedasheep(Dolly)fromanadultsheepuddercell.1997，TheNobelPrizeinPhysiologyorMedicine

"forhisdiscoveryofPrions–anewbiologicalprincipleofinfection"StanleyB.PrusinerUniv.ofCalifornia,SchoolofMedicine

USA1942-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