分子生物學(xué)的發(fā)展歷史

分子生物學(xué)的發(fā)展歷史第1頁(yè)/共40頁(yè)WhatisMolecularbiology?1.1.分子生物學(xué)的概念第2頁(yè)/共40頁(yè)Thetermhasmorethanonedefinition.Defineinbroadly：

understandbiologicalphenomenainmolecularterms(difficulttodistinguishfrombiochemistry)Defineinrestrictively：

thestudyofgenestructureandtheiractivitiesinmolecularlevelWhatisMolecularbiology?第3頁(yè)/共40頁(yè)遺傳學(xué)（genetics）生物化學(xué)（biochemistry）分子生物學(xué)（molecularbiology）第4頁(yè)/共40頁(yè)1.2.分子生物學(xué)發(fā)展簡(jiǎn)史第5頁(yè)/共40頁(yè)TransmissionGenetics傳遞遺傳學(xué)第6頁(yè)/共40頁(yè)In1865,GregorMendelpublishedMendelianinheritance(孟德?tīng)栠z傳定律).gardenpeaInheritanceoccurredthroughblendingofeachtraitoftheparentsintheoffspring.

Inheritanceisparticulate（微粒，微粒的）.Eachparentcontributesparticles,orgeneticunits,totheoffspring.1822-1884/RC/AB/BC/Gregor_Mendel.html第7頁(yè)/共40頁(yè)In1910,ThomasHuntMorganprovidedthefirstdefinitiveevidenceforthe

Chromosometheoryofinheritance

1933NobelPrize

inPhysiologyorMedicine

"forhisdiscoveriesconcerningtheroleplayedbytheChromosomeinheredity（遺傳）

,demonstratedthatgenesareonthechromosome"fruitfly(Drosophiamelanogaster)

1866-1945/medicine/laureates/1933/morgan-bio.html第8頁(yè)/共40頁(yè)MolecularGeneticsWhatgenesaremadeofandhowtheywork?第9頁(yè)/共40頁(yè)ThediscoveryofDNA1869,FriedrichMiescher

discoverednucleinandthemajorcomponentofnucleinisDNA.1844-1895http://www.fmi.ch/members/marilyn.vaccaro/ewww/index2.html第10頁(yè)/共40頁(yè)TheCompositionofGenes1944,OswaldAvery

demonstratedthatthechromosomeiscomposedofDNA.NotRNAorprotein!

FrederickGriffith肺炎球菌轉(zhuǎn)化試驗(yàn)1877-1955/dnaftb/concept_17/con17bio.html第11頁(yè)/共40頁(yè)Howdoesgeneswork?1902,ArchibaldGarrod,alcaptonuria（尿黑酸癥）GeorgeBeadleandE.L.Tatum,Neurospora（脈孢菌屬/鏈孢菌屬）one-gene/one-enzymehypothesisMostgenescontaintheinformationformakingonepolypeptide.第12頁(yè)/共40頁(yè)TheoverallstructureofDNA1951JamesWatson(23y)丹麥哥本哈根劍橋大學(xué)CavendishLab.FrancisCrick(35y)1953,doublehelix第13頁(yè)/共40頁(yè)"MolecularStructureofNucleicAcids:

AStructureforDeoxyriboseNucleicAcid"

(Nature,April25,1953.volume171:737-738.)

第14頁(yè)/共40頁(yè)RosalindFrankinX~rayphotographofDNAwithhighquality(核與磷酸連接成的扭曲繩子，每一節(jié)上都有配對(duì)的堿基)1951.King’sLab.LondonUniversityUKM.H.F.Wilkins第15頁(yè)/共40頁(yè)JamesWatson(34y)FrancisCrick(46y)MauriceWilkins(46y)1962NobelPrize第16頁(yè)/共40頁(yè)1958，MatthewMeselsonandFranklinStahlprovedthatDNAreplicationinbacteriafollowsthesemiconservativepathway.第17頁(yè)/共40頁(yè)MatthewMeselsonandFranklinStahlmorerecentlyFacultymemberatHarvardMechanismsofMolecularEvolutionFacultyChairforCBWStudiesFacultymemberatU.ofOregonMeioticRecombination第18頁(yè)/共40頁(yè)FrancoisJacobandSydneyBrennerTheribosomesarenonspecifictranslationmachinesthatcanmakedifferentproteins,accordingtotheinstructionsinthemRNAsthatvisittheribosomes.第19頁(yè)/共40頁(yè)Intheearly1960sMarshallNirenbergGobindKhoranaRobertW.Holley

fortheirinterpretationofthegeneticcodeanditsfunctioninproteinsynthesis.1968NobelPrizeinMedicine1927-1922-1922-第20頁(yè)/共40頁(yè)onegeneonepolypeptidenormalgenenormalfunctionmutantgenegeneticdisorderTechnique:genecloning第21頁(yè)/共40頁(yè)

HowardTemin(41y)DavidBaltimore(37y)Reversetranscription（引發(fā)癌癥的內(nèi)因）第22頁(yè)/共40頁(yè)TheNobelPrizeinChemistry1980"fortheircontributionsconcerningthedeterminationofbasesequencesinnucleicacids"WalterGilbert

FrederickSanger

1932-1918-第23頁(yè)/共40頁(yè)"forhisworkonthestructureofproteins,especiallythatofinsulin"TheNobelPrizeinChemistry1958FrederickSanger

1918-第24頁(yè)/共40頁(yè)1983.BarbaraMcClintock(86y)DNAtransposableelement第25頁(yè)/共40頁(yè)TheNobelPrizeinChemistry1989"fortheirdiscoveryofcatalyticpropertiesofRNARibozyme"SidneyAltman

ThomasR.CechYaleUniversity

NewHaven,CT,USAUniversityofColorado

Boulder,CO,USA1939-1947-第26頁(yè)/共40頁(yè)TheNobelPrizeinChemistry1993KaryB.Mullis

1944-"forhisinventionofthepolymerasechainreaction(PCR)method"第27頁(yè)/共40頁(yè)EdwardB.LewisChristianeNüsslein-Volhard

EricF.WieschausTheNobelPrizeinPhysiologyorMedicine,1995discoveredGeneticcontrolofearlydevelopmentinDrosophila（果蠅）第28頁(yè)/共40頁(yè)In1997,lanWilmutandcolleaguesclonedasheep(Dolly)fromanadultsheepuddercell.第29頁(yè)/共40頁(yè)1997，TheNobelPrizeinPhysiologyorMedicine

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

USA1942-第30頁(yè)/共40頁(yè)discoveredkeyregulatorsofthecellcycleLelandH.HartwellR.Timothy(Tim)HuntSirPaulM.NurseTheNobelPrizeinPhysiologyorMedicine2001第31頁(yè)/共40頁(yè)2002NobelPrizeJohnSulstonSydneyBrennerH.RobertHorvitzProgrammedCellDeath(PCD)anddevelopment第32頁(yè)/共40頁(yè)1.3.分子生物學(xué)的研究概況第33頁(yè)/共40頁(yè)還原論20世紀(jì)人類(lèi)對(duì)生命現(xiàn)象的認(rèn)識(shí)個(gè)體染色體基因DNAdNt基因的概念基因的本質(zhì)基因的功能逐步深刻認(rèn)識(shí)第34頁(yè)/共40頁(yè)人類(lèi)對(duì)生命現(xiàn)象的認(rèn)識(shí)還原論20世紀(jì)生命科學(xué)的飛躍了解整個(gè)生命現(xiàn)象的本質(zhì)仍然是零敲碎打研究策略（piecemeal

）第35頁(yè)/