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dc.contributor.authorBoddy, AMen
dc.contributor.authorHarrison, PWen
dc.contributor.authorMontgomery, Stephenen
dc.contributor.authorCaravas, JAen
dc.contributor.authorRaghanti, MAen
dc.contributor.authorPhillips, KAen
dc.contributor.authorMundy, Nicholasen
dc.contributor.authorWildman, DEen
dc.date.accessioned2017-05-08T10:11:30Z
dc.date.available2017-05-08T10:11:30Z
dc.date.issued2017-03-01en
dc.identifier.issn1759-6653
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/264131
dc.description.abstractThe adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey ($\textit{Cebus apella}$). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene-phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene-phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution.
dc.description.sponsorshipThis work was supported by the National Science Foundation, grant award numbers BCS-0751508, BCS-0827546, and BCS-1061370 for AMB and DEW. Professor Chet Sherwood (The George Washington University) provided useful guidance in the initial stages of this project. S.H.M. is grateful for support from a BBSRC doctoral training grant and a Research Fellowship from the Royal Commission for the Exhibition of 1851. N.I.M. is grateful for support from the Leverhulme Trust and Murray Edwards College, Cambridge.
dc.languageengen
dc.language.isoenen
dc.publisherOxford University Press
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rightsAttribution-NonCommercial 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/en
dc.subjectCebusen
dc.subjectadaptive evolutionen
dc.subjectbrain sizeen
dc.subjectcomparative genomicsen
dc.subjectmolecular evolutionen
dc.subjectprimate evolutionen
dc.titleEvidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primatesen
dc.typeArticle
prism.endingPage713
prism.issueIdentifier3en
prism.publicationDate2017en
prism.publicationNameGenome Biology and Evolutionen
prism.startingPage700
prism.volume9en
dc.identifier.doi10.17863/CAM.9493
dcterms.dateAccepted2017-02-23en
rioxxterms.versionofrecord10.1093/gbe/evx028en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc/4.0/en
rioxxterms.licenseref.startdate2017-03-01en
dc.contributor.orcidMontgomery, Stephen [0000-0002-5474-5695]
dc.contributor.orcidMundy, Nicholas [0000-0002-5545-1517]
dc.identifier.eissn1759-6653
rioxxterms.typeJournal Article/Reviewen
datacite.issupplementedby.doi10.5061/dryad.qt834en


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Attribution-NonCommercial 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial 4.0 International