dc.contributor.author | Capra, Emily Jordan | |
dc.contributor.author | Perchuk, Barrett | |
dc.contributor.author | Skerker, Jeffrey M. | |
dc.contributor.author | Laub, Michael T. | |
dc.date.accessioned | 2014-11-24T15:44:06Z | |
dc.date.available | 2014-11-24T15:44:06Z | |
dc.date.issued | 2012-07 | |
dc.date.submitted | 2012-04 | |
dc.identifier.issn | 00928674 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/91691 | |
dc.description.abstract | Orthologous 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.sponsorship | National Science Foundation (U.S.) (NSF Graduate Research Fellowship) | en_US |
dc.description.sponsorship | National Science Foundation (U.S.) (NSF CAREER Award) | en_US |
dc.language.iso | en_US | |
dc.publisher | Elsevier B.V. | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1016/j.cell.2012.05.033 | en_US |
dc.rights | Article 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.source | Elsevier | en_US |
dc.title | Adaptive Mutations that Prevent Crosstalk Enable the Expansion of Paralogous Signaling Protein Families | en_US |
dc.type | Article | en_US |
dc.identifier.citation | Capra, 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.department | Massachusetts Institute of Technology. Department of Biology | en_US |
dc.contributor.mitauthor | Capra, Emily Jordan | en_US |
dc.contributor.mitauthor | Perchuk, Barrett | en_US |
dc.contributor.mitauthor | Laub, Michael T. | en_US |
dc.relation.journal | Cell | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | Capra, Emily J.; Perchuk, Barrett S.; Skerker, Jeffrey M.; Laub, Michael T. | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-8288-7607 | |
dspace.mitauthor.error | true | |
mit.license | PUBLISHER_POLICY | en_US |
mit.metadata.status | Complete | |