Expression Patterns of Protein Kinases Correlate with Gene Architecture and Evolutionary Rates 英文参考文献.docVIP

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Expression Patterns of Protein Kinases Correlate with Gene Architecture and Evolutionary Rates 英文参考文献.doc

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Expression Patterns of Protein Kinases Correlate with Gene Architecture and Evolutionary Rates 英文参考文献

ExpressionPatternsofProteinKinasesCorrelatewith GeneArchitectureandEvolutionaryRates AlekseyY.Ogurtsov1.,LeonardoMarin?o-Ram?′rez1,GibbesR.Johnson2,DavidLandsman1,SvetlanaA. Shabalina1.*,NikolayA.Spiridonov2* 1NationalCenterforBiotechnologyInformation,NationalLibraryofMedicine,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica,2Divisionof TherapeuticProteins,CenterforDrugEvaluationandResearch,U.S.FoodandDrugAdministration,Bethesda,Maryland,UnitedStatesofAmerica Abstract Background: Protein kinase (PK) genes comprise thethird largest superfamily that occupy ,2%of the human genome. Theyencoderegulatoryenzymesthatcontrolavastvarietyofcellularprocessesthroughphosphorylationoftheirprotein substrates.ExpressionofPKgenesissubjecttocomplextranscriptionalregulationwhichisnotfullyunderstood. PrincipalFindings:OurcomparativeanalysisdemonstratesthatgenomicorganizationofregulatoryPKgenesdiffersfrom organizationofotherproteincodinggenes.PKgenesoccupylargergenomicloci,havelongerintrons,spacerregions,and encodelargerproteins.TheprimarytranscriptlengthofPKgenes,similartootherproteincodinggenes,inverselycorrelates with gene expression level and expression breadth, which is likely due to the necessity to reduce metabolic costs of transcriptionforabundantmessages.Onaverage,PKgenesevolveslowerthanotherproteincodinggenes.BreadthofPK expressionnegativelycorrelateswithrateofnon-synonymoussubstitutionsinproteincodingregions.Thisrateislowerfor highexpressionandubiquitousPKs,relativetolowexpressionPKs,andcorrelateswithdivergenceinuntranslatedregions. Conversely, rate of silent mutations is uniform in different PK groups, indicating that differing rates of non-synonymous substitutionsreflectvariationsinselectivepressure.Brainandtestisemployaconsiderablenumberoftissue-specificPKs, indicating high complexity of phosphorylation-dependent regulatory network in these organs. There are considerable differencesingenomicorganizationbetweenPKsup-regulatedinthetestisandbrain.PKgenesup-