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1、MBEAdvanceAccesspublishedNovember28,2013AGuidefortheDesignofEvolveandResequencingStudies1,1RobertKoflerandChristianSchlo¨tterer*1Institutfu¨rPopulationsgenetik,VetmeduniVienna,Vienna,Austria*Correspondingauthor:E-mail:christian.schloetterer@vetmeduni.ac.at.Associateeditor:JohnParsch
2、AbstractStandinggeneticvariationprovidesarichreservoirofpotentiallyusefulmutationsfacilitatingtheadaptationtonovelenvironments.Experimentalevolutionstudieshavedemonstratedthatrapidandstrongphenotypicresponsestoselec-tioncanalsobeobtainedinthelaboratory.Whencombinedwiththenext-gener
3、ationsequencingtechnology,theseexperimentspromisetoidentifytheindividuallocicontributingtoadaption.Nevertheless,untilnow,verylittleisknownaboutthedesignofsuchevolve&resequencing(E&R)studies.Here,weuseforwardsimulationsofentiregenomestoevaluatedifferentexperimentaldesignsthataimtoma
4、ximizethepowertodetectselectedvariants.Weshowthatlowlinkagedisequilibriuminthestartingpopulation,populationsize,durationoftheexperiment,andthenumberofreplicatesarethekeyfactorsindeterminingthepowerandaccuracyofE&Rstudies.Furthermore,replicationofE&Rismoreimportantfordetectingthetar
5、getsofselectionthanincreasingthepopulationsize.Usinganoptimizeddesign,beneficiallociwithaselectiveadvantageaslowass¼0:005canbeidentifiedatthenucleotidelevel.EvenwhenalargeDownloadedfromnumberoflociareselectedsimultaneously,upto56%canbereliablydetectedwithoutincurringlargenumbersoffal
6、sepositives.Ourcomputersimulationssuggestthat,withanadequateexperimentaldesign,E&Rstudiesareapowerfultooltoidentifyadaptivemutationsfromstandinggeneticvariationandtherebyprovideanexcellentmeanstoanalyzethetrajectoriesofselectedallelesinevolvingpopulations.http://mbe.oxfordjournals.
7、org/Keywords:experimentalevolution,evolve&resequencing,next-generationsequencing,bioinformatics,adaptation.Introductionidentifybeneficialloci.WebasethesimulationsonDrosophilamelanogaster,becauseitiswidelyusedinexperimentalevo-Theimportanceofstandinggeneticvariationtotheadapta-lution
8、studies(Rose1984;Burkeetal
