Evolution of Alternative Splicing Regulation Changes in Predicted Exonic Splicing Regulators Are Not Associated with Changes in Alternative Splicing Levels in Primates 英文参考文献.docVIP

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Evolution of Alternative Splicing Regulation Changes in Predicted Exonic Splicing Regulators Are Not Associated with Changes in Alternative Splicing Levels in Primates 英文参考文献.doc

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Evolution of Alternative Splicing Regulation Changes in Predicted Exonic Splicing Regulators Are Not Associated with Changes in Alternative Splicing Levels in Primates 英文参考文献

EvolutionofAlternativeSplicingRegulation:Changesin PredictedExonicSplicingRegulatorsAreNotAssociated withChangesinAlternativeSplicingLevelsinPrimates ManuelIrimia1*,JakobLewinRukov2,ScottWilliamRoy3* 1Departament de Gene`tica, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain, 2Molecular Evolution Group, Department of Biology, University of Copenhagen,Copenhagen,Denmark,3NationalCenterforBiotechnologyInformation,NationalLibraryofMedicine,NationalInstitutesofHealth,Bethesda,Maryland, UnitedStatesofAmerica Abstract Alternative splicing is tightly regulated in a spatio-temporal and quantitative manner. This regulation is achieved by a complexinterplaybetweenspliceosomal(trans)factorsthatbindtodifferentsequence(cis)elements.cis-elementsresidein bothintronsandexonsandmayeitherenhanceorsilencesplicing.Differentialcombinationsofcis-elementsallowsfora huge diversity of overall splicing signals, together comprising a complex ‘splicing code’. Many cis-elements have been identified,andtheireffectsonexoninclusionlevelsdemonstratedinreportersystems.However,theimpactofinterspecific differencesintheseelementsontheevolutionofalternativesplicinglevelshasnotyetbeeninvestigatedatgenomiclevel. Herewestudytheeffectofinterspecificdifferencesinpredictedexonicsplicingregulators(ESRs)onexoninclusionlevelsin humanandchimpanzee.Forthispurpose,wecompiledandstudiedcomprehensivedatasetsofpredictedESRs,identified byseveralcomputationalandexperimentalapproaches,aswellasmicroarraydataforchangesinalternativesplicinglevels betweenhumanandchimpanzee.Surprisingly,wefoundnoassociationbetweenchangesinpredictedESRsandchangesin alternative splicing levels. This observation holds across different ESR exon positions, exon lengths, and 59 splice site strengths.WesuggestthatthislackofassociationismainlyduetothegreatimportanceofcontextforESRfunctionality: manyESR-likemotifsinprimatesmayhavelittleornoeffectonsplicing,andthusinterspecificchangesatshort-timescales mayprimarilyoccurintheseeffective