Protein Complex Evolution Does Not Involve Extensive Network Rewiring 英文参考文献.docVIP

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Protein Complex Evolution Does Not Involve Extensive Network Rewiring 英文参考文献.doc

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Protein Complex Evolution Does Not Involve Extensive Network Rewiring 英文参考文献

ProteinComplexEvolutionDoesNotInvolveExtensive NetworkRewiring TeunisJ.P.vanDam1,2,BerendSnel1,3 * 1TheoreticalBiologyandBioinformaticsGroup,DepartmentofBiology,UtrechtUniversity,Utrecht,TheNetherlands,2DepartmentofPhysiologicalChemistryandCenter forBiomedicalGenetics,UniversityMedicalCenterUtrecht,Utrecht,TheNetherlands,3AcademicBiomedicalCentre,UtrechtUniversity,Utrecht,TheNetherlands Abstract Theformationofproteinsintostableproteincomplexesplaysafundamentalroleintheoperationofthecell.Thestudyof the degree of evolutionary conservation of protein complexes between species and the evolution of protein-protein interactions has been hampered by lack of comprehensive coverage of the high-throughput (HTP) technologies that measure the interactome. We show that new high-throughput datasets on protein co-purification in yeast have a substantially lower false negative rate than previous datasets when compared to known complexes. These datasets are thereforemoresuitabletoestimatetheconservationofproteincomplexmembershipthanhithertopossible.Weperform comparativegenomicsbetweencuratedproteincomplexesfromhumanandtheHTPdatainSaccharomycescerevisiaeto studytheevolutionofco-complexmemberships.Thisanalysisrevealedthatoutofthe5,960proteinpairsthatarepartof thesamecomplexinhuman,2,216areabsentbecausebothproteinslackanorthologinS.cerevisiae,whilefor1,828theco- complexmembershipisdisruptedbecauseoneofthetwoproteinslacksanortholog.Fortheremaining1,916proteinpairs, only 10% were never co-purified in the large-scale experiments. This implies a conservation level of co-complex membership of 90% when thegenes coding for the protein pairsthat participate in thesame protein complex arealso conserved.Weconcludethattheevolutionarydynamicsofproteincomplexesare,byandlarge,nottheresultofnetwork rewiring(i.e.acquisitionorlossofco-complexmemberships),butmainlyduetogenomicacquisitionorlossofgenescoding forsubunits.Wethusrevealevidenceforthetightinterrelationofgenomicandnetworkevolution. Citation:v