Genetic Basis of Hidden Phenotypic Variation Revealed by Increased Translational Readthrough in Yeast 英文参考文献.docVIP

GeneticBasisofHiddenPhenotypicVariationRevealed byIncreasedTranslationalReadthroughinYeast NoorossadatTorabi1,2,LeonidKruglyak1,3,4 * 1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey, United States ofAmerica, 2Department of Molecular Biology, Princeton University,Princeton,NewJersey,UnitedStatesofAmerica,3DepartmentofEcologyandEvolutionaryBiology,PrincetonUniversity,Princeton,NewJersey,UnitedStates ofAmerica,4HowardHughesMedicalInstitute,PrincetonUniversity,Princeton,NewJersey,UnitedStatesofAmerica Abstract Eukaryoticreleasefactors1and3,encodedbySUP45andSUP35,respectively,inSaccharomycescerevisiae,arerequiredfor translation termination. Recent studies have shown that, besides these two key factors, several genetic and epigenetic mechanisms modulate the efficiency of translation termination. These mechanisms, through modifying translation terminationfidelity,wereshowntoaffectvariouscellularprocesses,suchasmRNAdegradation,andinsomecasescould + conferabeneficialphenotypetothecell.Themoststudiedexampleofsuchamechanismis[PSI ],theprionconformation of Sup35p, which can have pleiotropic effects on growth that vary among different yeast strains. However, genetic loci underlying such readthrough-dependent, background-specific phenotypes have yet to be identified. Here, we used sup35C653R, a partial loss-of-function allele of the SUP35 previously shown to increase readthrough of stop codons and + recapitulate some [PSI ]-dependent phenotypes, to study the genetic basis of phenotypes revealed by increased translationalreadthroughintwodivergentyeaststrains:BY4724(alaboratorystrain)andRM11_1a(awinestrain).Wefirst identified growth conditions in which increased readthrough of stop codons by sup35C653R resulted in different growth responses between these two strains. We then used a recently developed linkage mapping technique, extreme QTL mapping (X-QTL), to identify readthrough-dependent loci for the observed growth difference