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1、InterferencelimitsresolutionofselectionpressuresfromlinkedneutraldiversityBenjaminH.Good1,AleksandraM.Walczak2,RichardA.Neher3,andMichaelM.Desai11DepartmentsofOrganismicandEvolutionaryBiologyandofPhysicsandFASCenterforSystemsBiology,HarvardUniversity2CNRS-LaboratoiredePhysi
2、queTheoriquedel'EcoleNormaleSuperieureand3MaxPlanckInstituteforDevelopmentalBiology,T•ubingen,Germany(Dated:August17,2018)Pervasivenaturalselectioncanstronglyin
uenceobservedpatternsofgeneticvariation,butthesee ectsremainpoorlyunderstoodwhenmultipleselectedvariantssegreg
3、ateinnearbyregionsofthegenome.Classicalpopulationgeneticsfailstoaccountforinterferencebetweenlinkedmutations,whichgrowsincreasinglysevereasthedensityofselectedpolymorphismsincreases.Here,wede-scribeasimplelimitthatemergeswheninterferenceiscommon,inwhichthe tnesse ectsofindi
4、vidualmutationsplayarelativelyminorrole.Instead,molecularevolutionisdeterminedbythevariancein tnesswithinthepopulation,de nedoverane ectivelyasexualsegmentofthegenome(alinkageblock").Weexploitthisinsensitivityinanewcoarse-grained"coalescentframework,whichapproximatesthee
5、ectsofmanyweaklyselectedmutationswithasmallernumberofstronglyselectedmutationswiththesamevariancein tness.Thisapproximationgeneratesaccurateandecientpredictionsforthegeneticdiversitythatcannotbesummarizedbyasimplereductionine ectivepopulationsize.However,theseresultssugges
6、tafundamentallimitonourabilitytore-solveindividualselectionpressuresfromcontemporarysequencedataalone,sinceawiderangeofparametersyieldnearlyidenticalpatternsofsequencevariability.Naturalselectionmaintainsexistingfunctionandpositiveselectionrespectively.Althoughinitiallyform
7、u-drivesadaptation,alteringpatternsofdiversityatthelatedforatwo-sitechromosome,bothcanbeextendedgeneticlevel.Evidencefrommicrobialevolutionexperi-tolargergenomesaslongastheselectedsitesaresu-ments[5]andnaturalpopulationsofnematodes[3],fruitcientlyrarethattheycanstillbetrea
8、tedindependently.
ies[44],andhumans[30]suggeststhatselectioniscom-Simpleanalytical
