A Toolbox Model of Evolution of Metabolic Pathways on Networks of Arbitrary Topology 英文参考文献.docVIP

AToolboxModelofEvolutionofMetabolicPathwayson NetworksofArbitraryTopology TinYauPang1,2,SergeiMaslov1* 1DepartmentofCondensedMatterPhysicsandMaterialsScience,BrookhavenNationalLaboratory,Upton,NewYork,UnitedStatesofAmerica,2DepartmentofPhysics andAstronomy,StonyBrookUniversity,StonyBrook,NewYork,UnitedStatesofAmerica Abstract In prokaryotic genomes the number of transcriptional regulators is known tobe proportional to the square of the total numberofprotein-codinggenes.Atoolboxmodelofevolutionwasrecentlyproposedtoexplainthisempiricalscalingfor metabolicenzymesandtheirregulators.Accordingtoitsrules,themetabolicnetworkofanorganismevolvesbyhorizontal transferofpathwaysfromotherspecies.Thesepathwaysarepartofalarger‘‘universal’’networkformedbytheunionofall species-specificnetworks.Itremainedtobeunderstood,however,howthetopologicalpropertiesofthisuniversalnetwork influence thescaling lawoffunctional contentofgenomes inthetoolbox model. Hereweanswer this questionby first analyzing the scaling properties of the toolbox model on arbitrary tree-like universal networks. We prove that critical branchingtopology,inwhichtheaveragenumberofupstreamneighborsofanodeisequaltoone,isbothnecessaryand sufficient for quadratic scaling. We further generalize the rules of the model to incorporate reactions with multiple substrates/products as well as branched and cyclic metabolic pathways. To achieve its metabolic tasks, the new model employsevolutionaryoptimizedpathwayswithminimalnumberofreactions.Numericalsimulationsofthisrealisticmodel on the universal network of all reactions in the KEGG database produced approximately quadratic scaling between the numberofregulatedpathwaysandthesizeofthemetabolicnetwork.Toquantifythegeometricalstructureofindividual pathways, we investigated the relationship between their number of reactions, byproducts, intermediate, and feedback metabolites.Ourresultsvalidateandexplaintheubiquitousappearanceofthequadraticscalingforabroadspectrumof topologiesofunde