Segregating YKU80 and TLC1 Alleles Underlying Natural Variation in Telomere Properties in Wild Yeast 英文参考文献.docVIP

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Segregating YKU80 and TLC1 Alleles Underlying Natural Variation in Telomere Properties in Wild Yeast 英文参考文献.doc

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Segregating YKU80 and TLC1 Alleles Underlying Natural Variation in Telomere Properties in Wild Yeast 英文参考文献

SegregatingYKU80andTLC1AllelesUnderlyingNatural VariationinTelomerePropertiesinWildYeast GianniLiti1*,SvastiHaricharan1,2,FranciscoA.Cubillos1,AnnaL.Tierney1,SarahSharp1,AlisonA. Bertuch2,LeopoldParts3,ElizabethBailes1,EdwardJ.Louis1* 1InstituteofGenetics,Queen’sMedicalCentre,UniversityofNottingham,Nottingham,UnitedKingdom,2BaylorCollegeofMedicine,Houston,Texas,UnitedStatesof America,3TheWellcomeTrustSangerInstitute,Hinxton,UnitedKingdom Abstract Inyeast,asinhumans,telomerelengthvariesamongindividualsandiscontrolledbymultipleloci.Inaquesttodefinethe extentofvariationintelomerelength,wescreened112wild-typeSaccharomycessensustrictoisolates.Wefoundextensive telomerelengthvariationinS.paradoxusisolates.Thisphenotypecorrelatedwiththeirgeographicorigin:Europeanstrains wereobservedtohaveextremelyshorttelomeres(,150bp),whereasAmericanisolateshadtelomeresapproximatelythree timesaslong(.400bp).InsertionsofaURA3geneneartelomeresallowedaccurateanalysisofindividualtelomerelengths andtelomerepositioneffect(TPE).CrossingtheAmericanandEuropeanstrainsresultedinF1sporeswithacontinuumof telomerelengthsconsistentwithwhat wouldbe predictedifmanyquantitativetraitloci (QTLs)wereinvolvedinlength maintenance. Variation in TPE is similarly quantitative but only weakly correlated with telomere length. Genotyping F1 segregants indicated several QTLs associated with telomere length and silencing variation. These QTLs include likely candidategenesbutalsomaptoregionswheretherearenoknowngenesinvolvedintelomericproperties.Wedetected transgressivesegregationforbothphenotypes.WevalidatedbyreciprocalhemizygositythatYKU80andTLC1aretelomere- length QTLs in the two S. paradoxus subpopulations. Furthermore, we propose that sequence divergence within the Ku heterodimer generates negative epistasis within one of the allelic combinations (American-YKU70 and European-YKU80) resultinginveryshorttelomeres. Citation: Liti G, Haricharan S, Cubillos FA, Tierney AL, Sharp S, et al. (2009) Segregating YKU80 a