Evolution of Complex Modular Biological Networks 英文参考文献.docVIP

EvolutionofComplexModularBiological Networks Arend Hintze, Christoph Adami* KeckGraduateInstituteofAppliedLifeSciences,Claremont,California,UnitedStatesofAmerica Biologicalnetworks have evolvedto behighlyfunctional within uncertain environments whileremaining extremely adaptable.Oneofthemaincontributorstotherobustnessandevolvabilityofbiologicalnetworksisbelievedtobe their modularity of function, with modules defined as sets of genes that are strongly interconnected but whose function is separable from those of other modules. Here, we investigate the in silico evolution of modularity and robustness in complex artificial metabolic networks that encode an increasing amount of information about their environment while acquiring ubiquitous features of biological, social, and engineering networks, such as scale-free edgedistribution,small-worldproperty,andfault-tolerance.Thesenetworksevolveinenvironmentsthatdifferintheir predictability,andallowustostudymodularityfromtopological,information-theoretic,andgene-epistaticpointsof view using new tools that do not depend on any preconceived notion of modularity. We find that for our evolved complex networks as well as for the yeast protein–protein interaction network, synthetic lethal gene pairs consist mostly of redundant genes that lie close to each other and therefore within modules, while knockdown suppressor genepairsarefartherapartandoftenstraddlemodules,suggestingthatknockdownrescueismediatedbyalternative pathwaysormodules.Thecombinationofnetworkmodularitytoolstogetherwithgeneticinteractiondataconstitutes apowerfulapproachtostudyanddissecttheroleofmodularityintheevolutionandfunctionofbiologicalnetworks. Citation:HintzeA,AdamiC(2008)Evolutionofcomplexmodularbiologicalnetworks.PLoSComputBiol4(2):e23.doi:10.1371/journal.pcbi.0040023 role they play within a network of modules and motifs, but also how these modules and their interconnections are Introduction Biological function is an extremely complicated conse- quenceofthea