Gene-X-ppt(Gene10-基因十)--Chapter25

Chapter25UsingtheGeneticCode25.2RelatedCodonsRepresentChemicallySimilarAminoAcids•Sixty-oneofthesixty-fourpossibletripletscodefortwentyaminoacids.•Threecodons(stopcodons)donotrepresentaminoacidsandcausetermination.FIGURE01:Thegeneticcodeistriplet25.2RelatedCodonsRepresentChemicallySimilarAminoAcids•Thegeneticcodewasfrozenatanearlystageofevolutionandisuniversal.•Mostaminoacidsarerepresentedbymorethanonecodon.FIGURE02:Aminoacidshave1-6codonseach25.2RelatedCodonsRepresentChemicallySimilarAminoAcids•Themultiplecodonsforanaminoacidaresynonymousandusuallyrelated.•third-basedegeneracy–Thelessereffectoncodonmeaningofthenucleotidepresentinthethird(3′)codonposition.•Chemicallysimilaraminoacidsoftenhaverelatedcodons,minimizingtheeffectsofmutation.25.3Codon–AnticodonRecognitionInvolvesWobbling•Multiplecodonsthatrepresentthesameaminoacidmostoftendifferatthethirdbaseposition(thewobblehypothesis).FIGURE03:Thirdbaseshavetheleastinfluenceoncodonmeanings25.3Codon–AnticodonRecognitionInvolvesWobbling•ThewobbleinpairingbetweenthefirstbaseoftheanticodonandthethirdbaseofthecodonresultsfromloosermonitoringofthepairingbyrRNAnucleotidesintheribosomalAsite.FIGURE04:WobbleinbasepairingallowsG-UpairstoformFIGURE05:Codon–anticodonpairinginvolveswobblingatthethirdposition25.4tRNAsAreProcessedfromLongerPrecursors•AmaturetRNAisgeneratedbyprocessingaprecursor.•The5′endisgeneratedbycleavagebytheendonucleaseRNAaseP.•The3′endisgeneratedbymultipleendonucleolyticandexonucleolyticcleavages,followedbyadditionofthecommonterminaltrinucleotideCCA.FIGURE06:BothendsoftRNAaregeneratedbyprocessing25.5tRNAContainsModifiedBases•tRNAscontainover90modifiedbases.•ModificationusuallyinvolvesdirectalterationoftheprimarybasesintRNA,buttherearesomeexceptionsinwhichabaseisremovedandreplacedbyanotherbase.FIGURE07:BasemodificationsintRNAvaryincomplexity.25.5tRNAContainsModifiedBases•KnownfunctionsofmodifiedbasesaretoconferincreasedstabilitytotRNAs,andtomodulatetheirrecognitionbyproteinsandotherRNAsinthetranslationalapparatus.25.6ModifiedBasesAffectAnticodon–CodonPairing•ModificationsintheanticodonaffectthepatternofwobblepairingandthereforeareimportantindeterminingtRNAspecificity.FIGURE08:InosinepairswiththreebasesFIGURE09:Modificationto2-thiouridinerestrictspairingtoA25.7ThereAreSporadicAlterationsoftheUniversalCode•Changesintheuniversalgeneticcodehaveoccurredinsomespecies.•Thesechangesaremorecommoninmitochondrialgenomes,whereaphylogenetictreecanbeconstructedforthechanges.FIGURE11:Changesinthegeneticcodeinmitochondriacanbetracedinphylogeny25.7ThereAreSporadicAlterationsoftheUniversalCode•Innucleargenomes,thechangesusuallyaffectonlyterminationcodons.FIGURE10:ChangesinthegeneticcodeusuallyinvolveStop/Nonesignals25.8NovelAminoAcidsCanBeInsertedatCertainStopCodons•TheinsertionofselenocysteineatsomeUGAcodonsrequirestheactionofanunusualtRNAincombinationwithseveralproteins.•TheunusualaminoacidpyrrolysinecanbeinsertedatcertainUAGcodons.•TheUGAcodonspecifiesbothselenocysteineandcysteineintheciliateEuplotescrassus.FIGURE12:SelBisspecificforSeleno-Cys-tRNA25.9tRNAsAreSelectivelyPairedwithAminoAcidsbyAminoacyl-tRNASynthetases•Aminoacyl-tRNAsynthetasesareafamilyofenzymesthatattachaminoacidtotRNA,generatingaminoacyl-tRNAinatwo-stepreactionthatusesenergyfromATP.•EachtRNAsynthetaseaminoacylatesallthetRNAsinanisoaccepting(orcognate)group,representingaparticularaminoacid.25.9tRNAsAreSelectivelyPairedwithAminoAcidsbyAminoacyl-tRNASynthetases•RecognitionoftRNAbytRNAsynthetasesisbasedonaparticularsetofnucleotides,thetRNA“identityset,”thatoftenareconcentratedintheacceptorstemandanticodonloopregionsofthemolecule.FIGURE13:Anaminoacyl-tRNAsynthetasechargestRNAwithanaminoacid25.10Aminoacyl-tRNASynthetasesFallintoTwoFamilies•Aminoacyl-tRNAsynthetasesaredividedintoclassIandclassIIfamiliesbasedonmutuallyexclusivesetsofsequencemotifsandstructuraldomains.FIGURE16:ClassI(Glu-tRNAsynthetase)&ClassII(Asp-tRNAsynthetase)FIGURE14:SeparationoftRNAsynthetasesintotwoclasses25.11SynthetasesUseProofreadingtoImproveAccuracy•Specificityofaminoacid-tRNApairingiscontrolledbyproofreadingreactionsthathydrolyzeincorrectlyformedaminoacyladenylatesandaminoacyl-tRNAs.•kineticproofreading–Aproofreadingmechanismthatdependsonincorrecteventsproceedingmoreslowlythancorrectevents,sothatincorrecteventsarereversedbeforeasubunitisaddedtoapolymericchain.FIGURE17:Kineticproofreadingreduceserrors25.11SynthetasesUseProofreadingtoImproveAccuracy•chemicalproofreading–Aproofreadingmechanisminwhichthecorrectioneventoccursaftertheadditionofanincorrectsubunittoapolymericchain,bymeansofreversingtheadditionreaction.FIGURE18:Synthetasesusechemicalproofreading25.12SuppressortRNAsHaveMutatedAnticodonsThatReadNewCodons•AsuppressortRNAtypicallyhasamutationintheanticodonthatchangesthecodonstowhichitresponds.25.12SuppressortRNAsHaveMutatedAnticodonsThatReadNewCodons•Whenthenewanticodoncorrespondstoaterminationcodon,anaminoacidisinsertedandthepolypeptidechainisextendedbeyondtheterminationcodon.–Thisresultsinnonsensesuppressionatasiteofnonsense