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Specificity and Evolvability in Eukaryotic Protein Interaction Networks 英文参考文献
SpecificityandEvolvabilityinEukaryoticProtein
InteractionNetworks
Pedro Beltrao*,Luis Serrano
EuropeanMolecularBiologyLaboratory,StructuresandComputationalBiologyProgram,Heidelberg,Germany
Progress in uncovering the protein interaction networks of several species has led to questions of what underlying
principles might govern their organization. Few studies have tried to determine the impact of protein interaction
network evolution on the observed physiological differences between species. Using comparative genomics and
structural information, we show here that eukaryotic species have rewired their interactomes at a fast rate of
approximately 10à5 interactions changed per protein pair, per million years of divergence. For Homo sapiens this
correspondsto103interactionschangedpermillionyears.Additionallywefindthatthespecificityofbindingstrongly
determinestheinteractionturnoverandthatdifferentbiologicalprocessesshowsignificantlydifferentlinkdynamics.
Inparticular,humanproteinsinvolvedinimmuneresponse,transport,andestablishmentoflocalizationshowsignsof
positiveselectionforchangeofinteractions.Ouranalysissuggeststhatasmalldegreeofmoleculardivergencecan
giverisetoimportantchangesatthenetworklevel.Weproposethatthepowerlawdistributionobservedinprotein
interaction networks could be partly explained by the cell’s requirement for different degrees of protein binding
specificity.
Citation:BeltraoP,SerranoL(2007)Specificityandevolvabilityineukaryoticproteininteractionnetworks.PLoSComputBiol3(2):e25.doi:10.1371/journal.pcbi.0030025
pressures do not constrain the exact cellular interactions,
butinsteadconstraintherequiredfunctionalcomplexesthat
Introduction
Manypartialprotein interactionmapsfor severaleukary-
otic species have now been published [1–9], and several
studies have tried to analyse the structure and evolution of
such networks on a topological level [10–16]. The massive
data produced by sequencing efforts has allowed for
comparison of different genomes, giving us
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