Selection for Robustness in Mutagenized RNA Viruses 英文参考文献.docVIP

SelectionforRobustness inMutagenizedRNAViruses Rafael Sanjua′n1,2,3[,Jose′ M.Cuevas4[,Victoria Furio′1,2,Edward C.Holmes5,6,Andre′sMoya1,2* 1 Institut Cavanilles de Biodiversitat i Biologia Evolutiva, Universitat de Vale`ncia, Vale`ncia, Spain, 2 Departament de Gene`tica, Universitat de Vale`ncia, Vale`ncia, Spain, 3InstitutodeBiolog?′aMolecularyCelulardePlantas,ConsejoSuperiordeInvestigacionesCient?′ficas,UniversidadPolite′cnica deVale`ncia,Vale`ncia,Spain,4Departmentof Zoology,UniversityofOxford,Oxford,UnitedKingdom,5CenterforInfectiousDiseaseDynamics,DepartmentofBiology,ThePennsylvaniaStateUniversity,UniversityPark, Pennsylvania,UnitedStatesofAmerica,6FogartyInternationalCenter,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica Mutational robustness is defined as the constancy of a phenotype in the face of deleterious mutations. Whether robustnesscanbedirectlyfavoredbynaturalselectionremainscontroversial.Theoryandinsilicoexperimentspredict that,athighmutationrates,slow-replicatinggenotypescanpotentiallyoutcompetefastercounterpartsiftheybenefit fromahigherrobustness.Here,weexperimentallyvalidatethishypothesis,dubbedthe‘‘survivaloftheflattest,’’using twopopulationsofthevesicularstomatitisRNAvirus.Characterizationoffitnessdistributionsandgeneticvariability indicatedthatonepopulationshowedahigherreplicationrate,whereastheotherwasmorerobusttomutation.The fasterreplicatoroutgrewitsrobustcounterpartinstandardcompetitionassays,buttheoutcomewasreversedinthe presenceofchemicalmutagens.Theseresultsshowthatselectioncandirectlyfavormutationalrobustnessandreveal anovelviralresistancemechanismagainsttreatmentbylethalmutagenesis. Citation:Sanjua′n R,CuevasJM,Furio′ V,HolmesEC,MoyaA(2007)SelectionforrobustnessinmutagenizedRNAviruses.PLoSGenet3(6):e93.doi:10.1371/journal.pgen. 0030093 experimentally explored in silico [15–17]. Such experiments have produced digital organisms with increased mutational Introduction Lethalmutagenesisconsistsofoverwhelmingv