Epistasis between Beneficial Mutations and the Phenotype-to-Fitness Map for a ssDNA Virus 英文参考文献.docVIP

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Epistasis between Beneficial Mutations and the Phenotype-to-Fitness Map for a ssDNA Virus 英文参考文献.doc

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Epistasis between Beneficial Mutations and the Phenotype-to-Fitness Map for a ssDNA Virus 英文参考文献

EpistasisbetweenBeneficialMutationsandthe Phenotype-to-FitnessMapforassDNAVirus DarinR.Rokyta1*,PaulJoyce2,S.BrianCaudle1,CraigMiller3,CraigJ.Beisel2,HollyA.Wichman3 1Department of Biological Science, Florida State University, Tallahassee, Florida, United States of America, 2Department of Mathematics and Statistics, University of Idaho,Moscow,Idaho,UnitedStatesofAmerica,3DepartmentofBiologicalSciences,UniversityofIdaho,Moscow,Idaho,UnitedStatesofAmerica Abstract Epistatic interactions between genes and individual mutations are major determinants of the evolutionary properties of genetic systems and have therefore been well documented, but few quantitative data exist on epistatic interactions betweenbeneficialmutations,presumablybecausesuchmutationsaresomuchrarerthandeleteriousones.Weexplored epistasisforbeneficialmutationsbyconstructinggenotypeswithpairsofmutationsthathadbeenpreviouslyidentifiedas beneficialtothessDNAbacteriophageID11andbymeasuringtheeffectsofthesemutationsaloneandincombination.We constructed 18 of the 36 possible double mutants for the nine available beneficial mutations. We found that epistatic interactionsbetweenbeneficialmutationswereallantagonistic—theeffectsofthedoublemutationswerelessthanthe sumsoftheeffectsoftheircomponentsinglemutations.Wefoundanumberofcasesofdecompensatoryinteractions,an extremeformofantagonisticepistasisinwhichthesecondmutationisactuallydeleteriousinthepresenceofthefirst.In thevastmajorityofcases,recombinationunitingtwobeneficialmutationsintothesamegenomewouldnotbefavoredby selection,astherecombinantcouldnotoutcompeteitsconstituentsinglemutations.Inanattempttounderstandthese results,wedevelopedasimplemodelinwhichthephenotypiceffectsofmutationsarecompletelyadditiveandepistatic interactionsariseasaresultoftheformofthephenotype-to-fitnessmapping.Wefoundthatamodelwithanintermediate phenotypicoptimumandadditivephenotypiceffectsprovidedagoodexplanationforourdataandtheobservedpatterns ofepistaticinteractions. Citation:RokytaDR