Resolving the Ortholog Conjecture Orthologs Tend to Be Weakly, but Significantly, More Similar in Function than Paralogs 英文参考文献.docVIP

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Resolving the Ortholog Conjecture Orthologs Tend to Be Weakly, but Significantly, More Similar in Function than Paralogs 英文参考文献.doc

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Resolving the Ortholog Conjecture Orthologs Tend to Be Weakly, but Significantly, More Similar in Function than Paralogs 英文参考文献

ResolvingtheOrthologConjecture:OrthologsTendtoBe Weakly,butSignificantly,MoreSimilarinFunction thanParalogs AdrianM.Altenhoff1,2,RomainA.Studer2,3,4,MarcRobinson-Rechavi2,3,ChristopheDessimoz1,2,5 * 1ETHZurich,DepartmentofComputerScience,Zu¨rich,Switzerland,2SwissInstituteofBioinformatics,Lausanne,Switzerland,3DepartmentofEcologyandEvolution, University of Lausanne, Lausanne, Switzerland, 4Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London, United Kingdom,5EMBL-EuropeanBioinformaticsInstitute,Hinxton,Cambridge,UnitedKingdom Abstract The function of most proteins is not determined experimentally, but is extrapolated from homologs. According to the ‘‘orthologconjecture’’,orstandardmodelofphylogenomics,proteinfunctionchangesrapidlyafterduplication,leadingto paralogs with different functions, while orthologs retain the ancestral function. We report here that a comparison of experimentallysupportedfunctionalannotationsamonghomologsfrom13genomesmostlysupportsthismodel.Weshow thattoanalyzeGOannotationeffectively,severalconfoundingfactorsneedtobecontrolled:authorshipbias,variationof GO term frequency among species, variation of background similarity among species pairs, and propagated annotation bias.Aftercontrollingforthesebiases,weobservethatorthologshavegenerallymoresimilarfunctionalannotationsthan paralogs.Thisisespeciallystrongforsub-cellularlocalization.Weobserveonlyaweakdecreaseinfunctionalsimilaritywith increasing sequence divergence. These findings hold over a large diversity of species; notably orthologs from model organismssuchasE.coli,yeastormousehaveconservedfunctionwithhumanproteins. Citation:AltenhoffAM,StuderRA,Robinson-RechaviM,DessimozC(2012)ResolvingtheOrthologConjecture:OrthologsTendtoBeWeakly,butSignificantly, MoreSimilarinFunctionthanParalogs.PLoSComputBiol8(5):e1002514.doi:10.1371/journal.pcbi.1002514 Editor:JonathanA.Eisen,UniversityofCaliforniaDavis,UnitedStatesofAmerica ReceivedOctober25,2011;A