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
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
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