Evolutionary Potential of a Duplicated Repressor-Operator Pair Simulating Pathways Using Mutation Data 英文参考文献.docVIP

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Evolutionary Potential of a Duplicated Repressor-Operator Pair Simulating Pathways Using Mutation Data 英文参考文献.doc

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Evolutionary Potential of a Duplicated Repressor-Operator Pair Simulating Pathways Using Mutation Data 英文参考文献

EvolutionaryPotentialofaDuplicated Repressor-OperatorPair:SimulatingPathways UsingMutationData Frank J.Poelwijk[,Daniel J.Kiviet[,Sander J.Tans* FOMInstituteforAtomicandMolecularPhysics(AMOLF),Amsterdam,Netherlands Ample evidence has accumulated for the evolutionary importance of duplication events. However, little is known about the ensuing step-by-step divergence process and the selective conditions that allow it to progress. Here we presentacomputationalstudyonthedivergenceoftworepressorsafterduplication.Acentralfeatureofourapproach is that intermediate phenotypes can be quantified through the use of in vivo measured repression strengths of Escherichiacolilacmutants.Evolutionarypathwaysareconstructedbymultipleroundsofsinglebasepairsubstitutions andselectionfortightandindependentbinding.Ouranalysisindicatesthatwhenaduplicatedrepressorco-diverges together with its binding site, the fitness landscape allows funneling to a new regulatory interaction with early increasesinfitness.Wefindthatneutralmutationsdonotplayanessentialrole,whichisimportantforsubstantial divergenceprobabilities.Byvaryingtheselectivepressurewecanpinpointthenecessaryingredientsfortheobserved divergence.Ourfindingsunderscoretheimportanceofcoevolutionarymechanismsinregulatorynetworks,andshould berelevantfortheevolutionofprotein-DNAaswellasprotein-proteininteractions. Citation:PoelwijkFJ,KivietDJ,TansSJ(2006)Evolutionarypotentialofaduplicatedrepressor-operatorpair:Simulatingpathwaysusingmutationdata.PLoSComputBiol 2(5):e58.DOI:10.1371/journal.pcbi.0020058 conditions that favor the evolution toward independent regulation. Interestingly, such regulatory divergence is Introduction Initially put forward by Stevens in 1951 [1] and later advocatedbyOhnoinhisseminalwork[2],geneduplication followed by functional divergence is now seen as a general mechanism for acquiring newfunctions [3]. Also,regulatory networks are thought to be shaped signi?cantly by genetic duplication [4]. For instance, sequence