DNA Scientists + Structure

DNAwasidentifiedasthegeneticmaterialthroughaseriesofexperiments.Griffithfindsa‘transformingprinciple.’Griffithexperimentedwiththebacteriathatcausepneumonia.Heusedtwoforms:theSform(deadly)andtheRform(notdeadly).AtransformingmaterialpassedfromdeadSbacteriatoliveRbacteria,makingthemdeadly.Griffithisolatedtwodifferentstrainsofthesamebacterialspecies.BothstrainsgrewverywellincultureplatesinGriffith’slab,butonlyoneofthestrainscausedpneumonia.-griffithknownforbacterialtransformationThedisease-causingbacteria(Sstrain)grewintosmoothcoloniesoncultureplates,whereastheharmlessbacteria(Rstrain)producedcolonieswithroughedges.WhenGriffithinjectedmicewithdisease-causingbacteria,themicesdevelopedpneumoniaanddied.Whenheinjectedmicewithharmlessbacteria,themicestayedhealthy.Perhaps,theS-strainbacteriaproducedatoxinthatmadethemicesick?Tofindout,Griffithranaseriesofexperiments.First,GriffithtookacultureoftheSstrain,heatedthecellstokillthem,andtheninjectedtheheat-killedbacteriaintolaboratorymice.Themicesurvived,suggestingthatthecauseofpneumoniawasnotatoxinfromthesedisease-causingbacteria.InGriffith’snextexperiment,hemixedtheheat-killed,S-strainbacteriawithlive,harmlessbacteriafromtheRstrainandinjectedthemixtureintolaboratorymice.Theinjectedmicedevelopedpneumonia,andmanydied.Griffithreasonedthatsomechemicalfactorthatcouldchangeharmlessbacteriain todisease-causingbacteriawastransferredfromtheheat-killedcellsoftheSstrainintothelivecellsoftheRstrain.Hecalledthisprocesstransformation,becauseonetypeofbacteriahadbeenchangedpermanentlyintoanother.Becausetheabilitytocause diseasewasinheritedbytheoffspringofthetransformedbacteria,Griffithconcludedthatthetransformingfactorhadtobeagene.AveryidentifiedDNAasthetransformingprinciple.AveryisolatedandpurifiedGriffith’stransformingprinciple.Averyperformedthreetestsonthetransformingprinciple.QualitativetestsshowedDNAwaspresent.ChemicaltestsshowedthechemicalmakeupmatchedthatofDNA.EnzymetestsshowedonlyDNA-degradingenzymesstoppedtransformation.Averyandhisteamextractedamixtureofvariousmoleculesfromtheheat-killedbacteriaandtreatedthismixturewithenzymesthatdestroyedproteins,lipids,carbohydrates,andsomeothermolecules,includingthenucleicacidRNA.Transformationstilloccurred.Avery’steamrepeatedtheexperimentusingenzymesthatwouldbreakdownDNA.WhentheydestroyedtheDNAinthemixture,transformationdidnotoccur.Therefore,DNAwasthetransformingfactor.SeveraldifferentscientistsrepeatedAvery’sexperiments.AlfredHersheyandMarthaChaseperformedthemostimportantoftheexperimentsrelatingtoAvery’sdiscovery.HersheyandChaseconfirmthatDNAisthegeneticmaterial.HersheyandChasestudiedvirusesthatinfectbacteria,orbacteriophages(BacteriaEater).-phage=virusWhena bacteriophageentersabacterium, itattachestothesurfaceofthebacterialcellandinjectsitsgeneticinformationintoit.Theviralgenesacttoproducemanynewbacteriophages,whichgraduallydestroythebacterium.Whenthecellsplitsopen,hundredsofnewvirusesburstout.AmericanscientistsAlfredHersheyandMarthaChasestudiedabacteriophagethatwascomposedofaDNAcoreandaproteincoat.Theywantedtodeterminewhichpartofthevirus—theproteincoatorDNAcore—enteredthebacterialcell.HersheyandChasegrewvirusesinculturescontainingradioactiveisotopesofphosphorus-32(P-32)sulfur-35(S-35)SinceproteinscontainalmostnophosphorusandDNAcontainsnosulfur,theseradioactivesubstancescouldbeusedasmarkers,enablingthescientiststotellwhichmoleculesactuallyenteredthebacteriaandcarriedthegeneticinformationofthevirus.IftheyfoundradioactivityfromS-35inthebacteria,itwouldmeanthatthevirus’sproteincoathadbeeninjectedintothebacteria.IftheyfoundP-32thentheDNAcorehadbeeninjected.Thetwoscientistsmixedthemarkedviruseswithbacterialcells,waitedafewminutesforthevirusestoinjecttheirgeneticmaterial,andthentestedthebacteriaforradioactivity.NearlyalltheradioactivityinthebacteriawasfromphosphorusP-32,themarkerfoundinDNA.HersheyandChaseconcludedthatthegeneticmaterialofthebacteriophagewasDNA,notprotein.WhatistheroleofDNAinheritance?TheDNAthatmakesupgenesmustbecapableofstoring,copying,andtransmittingthegeneticinformationinacell.Thesethreefunctionsareanalogoustothewayinwhichyoumightshareatreasuredbook.Theresearchofseveraldifferentscientistsledtowhatisknownaboutthestructureofdeoxyribonucleicacid,DNA.Chargaff’sRules:ErwinChargaffdiscoveredthatthepercentagesofadenineandthymine[T]basesarealmostequalinanysampleofDNA.Thesamethingistruefortheothertwonucleotides,guanine[G]andcytosine[C].Theobservationthat[A]=[T]and[G]=[C]becameknownasoneof“Chargaff’srules.”Franklin’sX-Rays:Inthe1950s,BritishscientistRosalindFranklinusedatechniquecalledX-raydiffractiontogetinformationaboutthestructureoftheDNAmolecule.X-raydiffractionrevealedanX-shapedpatternshowingthatthestrandsinDNAaretwistedaroundeachotherlikethecoilsofaspring.TheangleoftheX-shapedpatternsuggestedthattherearetwostrandsinthestructure.Othercluessuggestthatthenitrogenousbasesarenear thecenteroftheDNAmolecule.TheWorkofMauriceWilkins:WilkinsstudiedbiologicalmoleculeslikeDNAandvirusesusingavarietyofmicroscopesandspectrophotometers.HeeventuallybeganusingX-raystoproducediffractionimagesofDNAmolecules.TheX-raydiffractionimagesproducedbyhim,RosalindFranklin,andRaymondGoslingleadtothedeductionbyJamesWatsonandFrancisCrickofthe3-dimensionalhelicalnatureofDNA.Wilkinssharedthe1962NobelPrizeinPhysiologyorMedicinewithWatsonandCrick.TheWorkofWatsonandCrick:Atthesametime,JamesWatson,anAmericanbiologist,andFrancisCrick,aBritishphysicist,werealsotryingtounderstandthestructureofDNA.Theybuiltthree-dimensionalmodelsofthemolecule.Earlyin1953,withoutherpermission,WilkinsshowedWatsonacopyofFranklin’sX-raypattern.ThecluesinFranklin’sX-raypatternenabledWatsonandCricktobuildamodelthatexplainedthespecificstructureandpropertiesofDNA.WatsonandCrick’sbreakthroughmodelofDNAwasadoublehelix,inwhichtwostrandswerewoundaroundeachother.TheDouble-HelixModel:Adoublehelixlookslikeatwistedladder.Inthedouble-helixmodelofDNA,thetwostrandstwistaroundeachotherlikespiralstaircases.ThedoublehelixaccountedforFranklin’sX-raypatternandexplainsChargaff’sruleofbasepairingandhowthetwostrandsofDNAareheldtogether.HydrogenBonding:WatsonandCrickdiscoveredthathydrogenbondscouldformbetweencertainnitrogenousbases,providingjustenoughforcetoholdthetwoDNAstrandstogether.Hydrogenbondsarerelativelyweakchemicalforcesthatallowthetwostrandsofthehelixtoseparate.TheabilityofthetwostrandstoseparateiscriticaltoDNA’sfunctions.BasePairing:WatsonandCrick’smodelshowedthathydrogenbondscouldcreateanearlyperfectfitbetweennitrogenousbasesalongthecenterofthemolecule.Thesebondswouldformonlybetweencertainbasepairs—adeninewiththymine,andguaninewithcytosine.ThisnearlyperfectfitbetweenA–TandG–Cnucleotidesisknownasbasepairing,andisillustratedinthefigure.WatsonandCrickrealizedthatbasepairingexplainedChargaff’srule.Itgaveareasonwhy[A]=[T]and[G]=[C].Foreveryadenineinadouble-strandedDNAmolecule,therehadtobeexactlyonethymine.Foreachcytosine,therewasoneguanine.WhatarethechemicalcomponentsofDNA?DNAisanucleicacidmadeupofnucleotidesjoinedintolongstrandsorchainsbycovalentbonds.NucleicAcidsandNucleotides:Nucleicacidsarelong,slightlyacidicmoleculesoriginallyidentifiedincellnuclei.Nucleicacidsaremadeupofnucleotides,linkedtogethertoformlongchains.ThenucleotidesthatmakeupDNAareAdenine,thymine,guanine,andcytosine.DNA’snucleotidesaremadeupofthreebasiccomponents:a5-carbonsugarcalleddeoxyribose,aphosphategroup,andanitrogenousbase.ThenucleotidesinastrandofDNAarejoinedbycovalentbondsformedbetweentheirsugarandphosphategroups.TheCofthesugarinthenucleotidearenumbered#1-#5NitrogenousbasesattachatC1,PhosphatesattachatC5Toaddanucleotide,thenextphosphateisattachedatC3(theendwiththehydroxyl)Thestrandsaresaidtorun5’to3’ineachdirection5’to3’down;5’–3’up(Prime#referstotheConthesugar)NitrogenousBasesandCovalentBonds:DNAhasfourkindsofnitrogenousbases:adenine(A),guanine(G),cytosine(C),andthymine(T).Thenitrogenousbasesstickoutsidewaysfromthenucleotidechain.PurinesandPyrimidines:Thereare2groupsofDNAnucleotides–purinesandpyrimidines.Pyrimidines–TandC;composedof1carbonring.Purines–AandG;composedof2carbonrings.Purinescomplementpyrimidines(A–T;G–C)Thenucleotidescanbejoinedtogetherinanyorder,meaningthatanysequenceofbasesispossible.NucleotidesformdoublestrandbondedbyweakHbonds.A–Tby2Hbonds;G–Cby3HbondsThebasesmakeuptherungs.Thesugarsandphosphatesmakeupthesides.Itistwistedtoformadoublehelixortwistedladder.AntiparallelStrands:Inthedouble-helixmodel,thetwostrandsofDNAare“antiparallel”—theyrun inoppositedirections.Thisarrangementenablesthenitrogenousbasesonbothstrandstocomeintocontactatthecenterofthemolecule.Italsoallowseachstrandofthedoublehelixtocarryasequenceofnucleotides,arrangedalmostlikelettersinafour-letteralphabet.

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