Robustness Can Evolve Gradually in Complex Regulatory Gene Networks with Varying Topology 英文参考文献.docVIP

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Robustness Can Evolve Gradually in Complex Regulatory Gene Networks with Varying Topology 英文参考文献.doc

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Robustness Can Evolve Gradually in Complex Regulatory Gene Networks with Varying Topology 英文参考文献

RobustnessCanEvolveGraduallyinComplex RegulatoryGeneNetworkswithVarying Topology Stefano Ciliberti1,2[,Olivier C.Martin1,2,3,4,5[,Andreas Wagner6* 1LaboratoiredePhysiqueThe′oique etMode`les Statistiques,UniversiteParis-Sud,Orsay,France,2CentreNationaldelaRechercheScientifique,UniversiteParis-Sud,Orsay, France,3LaboratoiredeGenetiqueVegetaleduMoulon,UniversiteParis-Sud,Gif-sur-Yvette,France,4L’InstitutNationaldelaRechercheAgronomique,UniversiteParis-Sud, Gif-sur-Yvette,5CentreNationaldelaRechercheScientifique,UniversiteParis-Sud,Gif-sur-Yvette,France,6DepartmentofBiochemistry,UniversityofZurich,Switzerland The topology of cellular circuits (the who-interacts-with-whom) is key to understand their robustness to both mutationsandnoise.Thereasonisthatmanybiochemicalparametersdrivingcircuitbehaviorvaryextensivelyandare thusnotfine-tuned.Existingworkinthisareaaskstowhatextentthefunctionofanyonegivencircuitisrobust.Butis highrobustnesstrulyremarkable,orwoulditbeexpectedfor manycircuitsofsimilartopology? Andhowcanhigh robustnesscomeaboutthroughgradualDarwinianevolutionthatchangescircuittopologygradually,oneinteraction atatime?Wehereaskthesequestionsforamodeloftranscriptionalregulationnetworks,inwhichweexploremillions of different network topologies. Robustness to mutations and noise are correlated in these networks. They show a skeweddistribution,withaverysmallnumberofnetworksbeingvastlymorerobustthantherest.Allnetworksthat attain a given gene expression state can be organized into a graph whose nodes are networks that differ in their topology.Remarkably,thisgraphisconnectedandcanbeeasilytraversedbygradualchangesofnetworktopologies. Thus,robustnessisanevolvableproperty.Thisconnectednessandevolvabilityofrobustnetworksmaybeageneral organizationalprincipleofbiologicalnetworks.Inaddition,itexistsalsoforRNAandproteinstructures,andmaythus beageneralorganizationalprincipleofallbiologicalsystems. Citation:CilibertiS,MartinOC,WagnerA(2007)Robustnesscanevolvegraduallyincom