DNA双螺旋结构--发表在NATURE

1、1953年沃森和克里克发现DNA双螺旋结构发表在Nature上的论文2April1953MOLECULARSTRUCTUREOFNUCLEICACIDSAStructureforDeoxyriboseNucleicAcidThkligurvispurely<)UqramTi)atric.Th*Iworibbonssymbalizetheuv。phosphate-ehaiii«,anUtheharb加ontnlrodtstlicpalraofbasesholdingthechin3together.Tlicvgrtimllinemarkdthefibre#*MWewishtosu

2、ggestastructureforthesaltofdeoxyribosenucleicacid(D.N.A.).Thisstructurehasnovelfeatureswhichareofconsiderablebiologicalinterest.AstructurefornucleicacidhasalreadybeenproposedbyPaulingandCorey(1).Theykindlymadetheirmanuscriptavailabletousinadvanceofpublication.Theirmodelconsistsofthreeintertwinedchai

3、ns,withthephosphatesnearthefibreaxis,andthebasesontheoutside.Inouropinion,thisstructureisunsatisfactoryfortworeasons:(1)WebelievethatthematerialwhichgivestheX-raydiagramsisthesalt,notthefreeacid.Withouttheacidichydrogenatomsitisnotclearwhatforceswouldholdthestructuretogether,especiallyasthenegativel

4、ychargedphosphatesneartheaxiswillrepeleachother.(2)SomeofthevanderWaalsdistancesappeartobetoosmall.Anotherthree-chainstructurehasalsobeensuggestedbyFraser(inthepress).Inhismodelthephosphatesareontheoutsideandthebasesontheinside,linkedtogetherbyhydrogenbonds.Thisstructureasdescribedisratherill-define

5、d,andforthisreasonweshallnotcommentonit.Wewishtoputforwardaradicallydifferentstructureforthesaltofdeoxyribosenucleicacid.Thisstructurehastwohelicalchainseachcoiledroundthesameaxis(seediagram).Wehavemadetheusualchemicalassumptions,namely,thateachchainconsistsofphosphatediestergroupsjoining?-D-deoxyri

6、bofuranoseresidueswith3',5'linkages.Thetwochains(butnottheirbases)arerelatedbyadyadperpendiculartothefibreaxis.Bothchainsfollowright-handedhelices,butowingtothedyadthesequencesoftheatomsinthetwochainsruninoppositedirections.EachchainlooselyresemblesFurberg's2modelNo.1;thatis,thebasesareo

7、ntheinsideofthehelixandthephosphatesontheoutside.TheconfigurationofthesugarandtheatomsnearitisclosetoFurberg's'standardconfiguration',thesugarbeingroughlyperpendiculartotheattachedbase.Thereisaresidueoneachevery3.4A.inthez-direction.Wehaveassumedanangleof36°betweenadjacentresiduesin

8、thesamechain,sothatthestructurerepeatsafter10residuesoneachchain,thatis,after34A.Thedistanceofaphosphorusatomfromthefibreaxisis10A.Asthephosphatesareontheoutside,cationshaveeasyaccesstothem.Thestructureisanopenone,anditswatercontentisratherhigh.Atlowerwatercontentswewouldexpectthebasestotiltsothatth

9、estructurecouldbecomemorecompact.Thenovelfeatureofthestructureisthemannerinwhichthetwochainsareheldtogetherbythepurineandpyrimidinebases.Theplanesofthebasesareperpendiculartothefibreaxis.Thearejoinedtogetherinpairs,asinglebasefromtheotherchain,sothatthetwoliesidebysidewithidenticalz-co-ordinates.One

10、ofthepairmustbeapurineandtheotherapyrimidineforbondingtooccur.Thehydrogenbondsaremadeasfollows:purineposition1topyrimidineposition1;purineposition6topyrimidineposition6.Ifitisassumedthatthebasesonlyoccurinthestructureinthemostplausibletautomericforms(thatis,withtheketoratherthantheenolconfigurations

11、)itisfoundthatonlyspecificpairsofbasescanbondtogether.Thesepairsare:adenine(purine)withthymine(pyrimidine),andguanine(purine)withcytosine(pyrimidine).Inotherwords,ifanadenineformsonememberofapair,oneitherchain,thenontheseassumptionstheothermembermustbethymine;similarlyforguanineandcytosine.Thesequen

12、ceofbasesonasinglechaindoesnotappeartoberestrictedinanyway.However,ifonlyspecificpairsofbasescanbeformed,itfollowsthatifthesequenceofbasesononechainisgiven,thenthesequenceontheotherchainisautomaticallydetermined.Ithasbeenfoundexperimentally(3,4)thattheratiooftheamountsofadeninetothymine,andtheration

13、ofguaninetocytosine,arealwaysberyclosetounityfordeoxyribosenucleicacid.Itisprobablyimpossibletobuildthisstructurewitharibosesugarinplaceofthedeoxyribose,astheextraoxygenatomwouldmaketoocloseavanderWaalscontact.ThepreviouslypublishedX-raydata(5,6)ondeoxyribosenucleicacidareinsufficientforarigoroustes

14、tofourstructure.Sofaraswecantell,itisroughlycompatiblewiththeexperimentaldata,butitmustberegardedasunproveduntilithasbeencheckedagainstmoreexactresults.Someofthesearegiveninthefollowingcommunications.Wewerenotawareofthedetailsoftheresultspresentedtherewhenwedevisedourstructure,whichrestsmainlythough

15、notentirelyonpublishedexperimentaldataandstereochemicalarguments.Ithasnotescapedournoticethatthespecificpairingwehavepostulatedimmediatelysuggestsapossiblecopyingmechanismforthegeneticmaterial.Fulldetailsofthestructure,includingtheconditionsassumedinbuildingit,togetherwithasetofco-ordinatesfortheato

16、ms,willbepublishedelsewhere.WearemuchindebtedtoDr.JerryDonohueforconstantadviceandcriticism,especiallyoninteratomicdistances.WehavealsobeenstimulatedbyaknowledgeofthegeneralnatureoftheunpublishedexperimentalresultsandideasofDr.M.H.F.Wilkins,Dr.R.E.Franklinandtheirco-workersatKing'sCollege,London

17、.Oneofus(J.D.W.)hasbeenaidedbyafellowshipfromtheNationalFoundationforInfantileParalysis.J.D.WATSONF.H.C.CRICKMedicalResearchCouncilUnitfortheStudyofMolecularStructureofBiologicalSystems,CavendishLaboratory,Cambridge.April2.1. Pauling,L.,andCorey,R.B.,Nature,171,346(1953);Proc.U.S.Nat.Acad.Sci.,39,84

18、(1953).2. Furberg,S.,ActaChem.Scand.,6,634(1952).3. Chargaff,E.,forreferencesseeZamenhof,S.,Brawerman,G.,andChargaff,E.,Biochim.etBiophys.Acta,9,402(1952).4. Wyatt,G.R.,J.Gen.Physiol.,36,201(1952).5. Astbury,W.T.,Symp.Soc.Exp.Biol.1,NucleicAcid,66(Camb.Univ.Press,1947).6. Wilkins,M.H.F.,andRandall,J

19、.T.,Biochim.etBiophys.Acta,10,192(1953).VOL171,page737,1953Theyear1953couldbesaidtomark,inbiologyatleast,theendofhistory.HereisJamesWatsonandFrancisCrick'spaperonthestructureofDNA,whichusheredinthenewerawiththecelebratedunderstatementneartheend.(aspublishedinNATUREmagazine)我们拟提出脱氧核糖核酸（DNA）盐的一种结构

20、。这种结构的崭新特点具有重要的生物学意义。鲍林和考瑞曾提出过一个核酸结构。他们在发表这一结构之前，欣然将手稿送给我们一阅。他们的模型包含磷酸接近纤维袖，碱基在外周的三条多核甘酸链。我们觉得这样的结构是不够满意的，其理由有二：（1）我们认为进行过X射线衍射分析的样品是DNA的盐而不是游离的酸。没有酸性氢原子，接近轴心并带负电的磷酸会相互排斥。在这样的条件下，究竟是什么力量把这种结构维系在一起，尚不清楚。（2）范德瓦尔力距似显太小。弗雷泽曾提出过另外一种三条多核甘酸链的结构（将出版）。在他的模型中，磷酸在外边，碱基在内部，并由氢键维系着。他描述的这种结构也不够完善，因此，我们将不予评论。我们拟提出一个完全不同的脱氧核糖核酸盐的结构。该结构具有绕同一轴心旋转的两条螺旋链（见图）。根据化学常识我们假定，每条链包括联结3-D-脱氧吠喃核糖的3'