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dc.contributor.authorCapra, Emily Jordan
dc.contributor.authorPerchuk, Barrett
dc.contributor.authorSkerker, Jeffrey M.
dc.contributor.authorLaub, Michael T.
dc.date.accessioned2014-11-24T15:44:06Z
dc.date.available2014-11-24T15:44:06Z
dc.date.issued2012-07
dc.date.submitted2012-04
dc.identifier.issn00928674
dc.identifier.urihttp://hdl.handle.net/1721.1/91691
dc.description.abstractOrthologous proteins often harbor numerous substitutions, but whether these differences result from neutral or adaptive processes is usually unclear. To tackle this challenge, we examined the divergent evolution of a model bacterial signaling pathway comprising the kinase PhoR and its cognate substrate PhoB. We show that the specificity-determining residues of these proteins are typically under purifying selection but have, in α-proteobacteria, undergone a burst of diversification followed by extended stasis. By reversing mutations that accumulated in an α-proteobacterial PhoR, we demonstrate that these substitutions were adaptive, enabling PhoR to avoid crosstalk with a paralogous pathway that arose specifically in α-proteobacteria. Our findings demonstrate that duplication and the subsequent need to avoid crosstalk strongly influence signaling protein evolution. These results provide a concrete example of how system-wide insulation can be achieved postduplication through a surprisingly limited number of mutations. Our work may help explain the apparent ease with which paralogous protein families expanded in all organisms.en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (NSF Graduate Research Fellowship)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (NSF CAREER Award)en_US
dc.language.isoen_US
dc.publisherElsevier B.V.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.cell.2012.05.033en_US
dc.rightsArticle is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.en_US
dc.sourceElsevieren_US
dc.titleAdaptive Mutations that Prevent Crosstalk Enable the Expansion of Paralogous Signaling Protein Familiesen_US
dc.typeArticleen_US
dc.identifier.citationCapra, Emily J., Barrett S. Perchuk, Jeffrey M. Skerker, and Michael T. Laub. “Adaptive Mutations That Prevent Crosstalk Enable the Expansion of Paralogous Signaling Protein Families.” Cell 150, no. 1 (July 2012): 222–232. © 2012 Elsevier Inc.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorCapra, Emily Jordanen_US
dc.contributor.mitauthorPerchuk, Barretten_US
dc.contributor.mitauthorLaub, Michael T.en_US
dc.relation.journalCellen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsCapra, Emily J.; Perchuk, Barrett S.; Skerker, Jeffrey M.; Laub, Michael T.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-8288-7607
dspace.mitauthor.errortrue
mit.licensePUBLISHER_POLICYen_US
mit.metadata.statusComplete


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