Selective Constraint on the Upstream Open Reading Frames That Overlap with Coding Sequences in Animals 英文参考文献.docVIP

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Selective Constraint on the Upstream Open Reading Frames That Overlap with Coding Sequences in Animals 英文参考文献.doc

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Selective Constraint on the Upstream Open Reading Frames That Overlap with Coding Sequences in Animals 英文参考文献

SelectiveConstraintontheUpstreamOpenReading FramesThatOverlapwithCodingSequencesinAnimals Ming-KungHsu1,Feng-ChiChen1,2,3* 1DivisionofBiostatisticsandBioinformatics,InstituteofPopulationHealthSciences,NationalHealthResearchInstitutes,Zhunan,MiaoliCounty,Taiwan,2Departmentof LifeSciences,NationalChiao-TungUniversity,Hsinchu,Taiwan,3DepartmentofDentistry,ChinaMedicalUniversity,Taichung,Taiwan Abstract Upstreamopenreadingframes(uORFs)aretranslationalregulatoryelementslocatedin59untranslatedregions.Theycan significantly repress the translation of the downstream coding sequences (CDS), and participate in the spatio-temporal regulationsofproteintranslation.Notwithstandingthisbiologicalsignificance,theselectiveconstraintonuORFsremains underexplored.Particularly,theuORFsthatpartiallyoverlapwithCDSwithadifferentreadingframe(overlappinguORFs,or ‘‘VuORFs’’)mayleadtostrongtranslationalinhibitionorN-terminaltruncationofthepeptidesencodedbytheaffectedCDS. By analyzing VuORF-containing transcripts (designated as ‘‘VuORF transcripts’’) in human, mouse, and fruit fly, we demonstrate that VuORFs are in general slightly deleterious - the proportion of genes that encode at least one VuORF transcript is significantly smaller than expected in all of the three examined species. In addition, this proportion is significantlysmallerinfruitflythaninmammals,indicatingahigherefficiencyofremovingVuORFsintheformerspecies becauseofitslargereffectivepopulationsize.Furthermore,thedeleteriouseffectofaVuORFdependsonthesequence contextofitsstartcodon(VuAUG).VuORFswithanoptimalVuAUGcontextaremorestronglydisfavoredthanthosewitha suboptimalcontextinallofthethreeexaminedspecies.Andthepropensitytoremoveoptimal-contextVuAUGsisstronger infruitflythaninmammals.Intriguingly,however,thecurrentlyobservableoptimal-contextVuAUGs(butnotsuboptimal- contextVuAUGs)aremoreconservedthanexpected.TheseobservationssuggestthattheregulatoryfunctionsofVuORFs mayhavebeengainedfortuitouslyinorganismswithasmalleffectivepopulati