Evolutionary Accessibility of Mutational Pathways 英文参考文献.docVIP

EvolutionaryAccessibilityofMutationalPathways JasperFranke1,AlexanderKlo¨zer1,J.ArjanG.M.deVisser2,JoachimKrug1* 1InstituteofTheoreticalPhysics,UniversityofCologne,Ko¨ln,Germany,2LaboratoryofGenetics,WageningenUniversity,Wageningen,Netherlands Abstract Functionaleffectsofdifferentmutationsareknowntocombinetothetotaleffectinhighlynontrivialways.Forthetrait underevolutionaryselection(‘fitness’),measuredvaluesoverallpossiblecombinationsofasetofmutationsyieldafitness landscape that determines which mutational states can be reached from a given initial genotype. Understanding the accessibilitypropertiesoffitnesslandscapesisconceptuallyimportantinansweringquestionsaboutthepredictabilityand repeatability ofevolutionaryadaptation.Herewetheoreticallyinvestigateaccessibility ofthegloballyoptimalstateona widevarietyofmodellandscapes,includinglandscapeswithtunableruggednessaswellasneutral‘holey’landscapes.We defineamutationalpathwaytobeaccessibleifitcontainstheminimalnumberofmutationsrequiredtoreachthetarget genotype,andiffitnessincreasesineachmutationalstep.Underthisdefinitionaccessibilityishigh,inthesensethatatleast one accessible pathway exists with a substantial probability that approaches unity as the dimensionality of the fitness landscape (setby thenumberofmutationalloci)becomeslarge.Atthesametimethenumberofalternativeaccessible pathwaysgrowswithoutbounds.Wetestthemodelpredictionsagainstanempirical8-locusfitnesslandscapeobtainedfor the filamentous fungus Aspergillus niger. By analyzing subgraphs of the full landscape containing different subsets of mutations, we are able to probe the mutational distance scale in the empirical data. The predicted effect of high accessibilityissupportedbytheempiricaldataandisveryrobust,whichwearguereflectsthegenerictopologyofsequence spaces. Together with the restrictive assumptions that lie in our definition of accessibility, this implies that the globally optimalconfigurationshouldbeaccessibletogenomewideevolution,buttherepeatabilit