Protein–Protein Interactions More Conserved within Species than across Species 英文参考文献.docVIP

Protein–ProteinInteractionsMoreConserved withinSpeciesthanacrossSpecies Sven Mika1,2,*,Burkhard Rost2,3,4 1 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York, United States of America, 2 Columbia University Center for Computational Biology and Bioinformatics, Irvine Cancer Center, New York, New York, United States of America, 3 Institute of Physical Biochemistry, University Witten/ Herdecke,Witten,Germany,4NorthEastStructuralGenomicsConsortium,NewYork,NewYork,UnitedStatesofAmerica Experimental high-throughput studies of protein–protein interactions are beginning to provide enough data for comprehensive computational studies. Today, about ten large data sets, each with thousands of interacting pairs, coarselysampletheinteractionsinfly,human,worm,andyeast.Anotherabout55,000pairsofinteractingproteins have been identified by more careful, detailed biochemical experiments. Most interactions are experimentally observed in prokaryotes and simple eukaryotes; very few interactions are observed in higher eukaryotes such as mammals.Itiscommonlyassumedthatpathwaysinmammalscanbeinferredthroughhomologytomodelorganisms, e.g.theexperimentalobservationthattwoyeastproteinsinteractistransferredtoinferthatthetwocorresponding proteinsinhumanalsointeract.Twopairsforwhichtheinteractionisconservedareoftendescribedasinterologs.The goal of this investigation was a large-scale comprehensive analysis of such inferences, i.e. of the evolutionary conservation of interologs. Here, we introduced a novel score for measuring the overlap between protein–protein interactiondatasets.Thismeasureappearedtoreflecttheoverallqualityofthedataandwasthebasisforourtwo surprising results from our large-scale analysis. Firstly, homology-based inferences of physical protein–protein interactionsappearedfarlesssuccessfulthanexpected.Infact,suchinferenceswereaccurateonlyforextremelyhigh levels of sequence similarity. Secondly, and most surprisingly, the identification of i