Adaptation for Protein Synthesis Efficiency in a Naturally Occurring Self-Regulating Operon 英文参考文献.docVIP

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Adaptation for Protein Synthesis Efficiency in a Naturally Occurring Self-Regulating Operon 英文参考文献.doc

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Adaptation for Protein Synthesis Efficiency in a Naturally Occurring Self-Regulating Operon 英文参考文献

AdaptationforProteinSynthesisEfficiencyinaNaturally OccurringSelf-RegulatingOperon DorotaHerman1,2,3,ChristopherM.Thomas1,DovJ.Stekel2* 1SchoolofBiosciences,UniversityofBirmingham,Birmingham,UnitedKingdom,2SchoolofBiosciences,UniversityofNottingham,SuttonBonington,Leicestershire, UnitedKingdom,3DepartmentofPlantSystemsBiology,VIB–GhentUniversity,Ghent,Belgium Abstract ThekorABoperoninRK2plasmidsisabeautifulnaturalexampleofanegativelyandcooperativelyself-regulatingoperon.It hasbeenparticularlywellcharacterizedbothexperimentallyandwithmathematicalmodels.Wehavecarriedoutadetailed investigation of the role of the regulatory mechanism using a biologically grounded mechanistic multi-scale stochastic modelthatincludesplasmidgeneregulationandreplicationinthecontextofhostgrowthandcelldivision.Weusethe modeltocomparefourhypothesesfortheactionoftheregulatorymechanism:increasedrobustnesstoextrinsicfactors, decreasedproteinfluctuations,fasterresponse-timeoftheoperonandreducedhostburdenthroughimprovedefficiencyof proteinproduction.Wefindthatthestrongestimpactofallelementsoftheregulatoryarchitectureisonimprovingthe efficiencyofproteinsynthesisbyreductioninthenumberofmRNAmoleculesneededtobeproduced,leadingtoagreater thanten-foldreductioninhostenergyrequiredtoexpresstheseplasmidproteins.Asmallerbutstillsignificantroleisseen forspeedingresponsetimes,butthisisnotmateriallyimprovedbythecooperativity.Theself-regulatingmechanismshave theleastimpactonproteinfluctuationsandrobustness.Whilereductionofhostburdenisevidentinaplasmidcontext, negativeself-regulationisawidelyseenmotifforchromosomalgenes.Weproposethatanimportantevolutionarydriver fornegativelyself-regulatedgenesistoimprovetheefficiencyofproteinsynthesis. Citation:HermanD,ThomasCM,StekelDJ(2012)AdaptationforProteinSynthesisEfficiencyinaNaturallyOccurringSelf-RegulatingOperon.PLoSONE7(11): e49678.doi:10.1371/journal.pone.0049678 Editor:MarkIsalan,CenterforGenomicRegulation,Spain ReceivedJune22,2012;AcceptedOctober15,2012;PublishedNo