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dc.contributor.advisor Matsunami, Hiroaki en_US
dc.contributor.author Adipietro, KA
dc.contributor.author Mainland, JD
dc.contributor.author Matsunami, H
dc.coverage.spatial United States
dc.date.accessioned 2012-09-04T13:15:49Z
dc.date.issued 2012
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/22807691
dc.identifier PGENETICS-D-11-02178
dc.identifier.citation PLoS Genet, 2012, 8 (7), pp. e1002821 - ?
dc.identifier.uri http://hdl.handle.net/10161/5830
dc.description Dissertation en_US
dc.description.abstract The mammalian odorant receptor (OR) repertoire is an attractive model to study evolution, because ORs have been subjected to rapid evolution between species, presumably caused by changes of the olfactory system to adapt to the environment. However, functional assessment of ORs in related species remains largely untested. Here we investigated the functional properties of primate and rodent ORs to determine how well evolutionary distance predicts functional characteristics. Using human and mouse ORs with previously identified ligands, we cloned 18 OR orthologs from chimpanzee and rhesus macaque and 17 mouse-rat orthologous pairs that are broadly representative of the OR repertoire. We functionally characterized the in vitro responses of ORs to a wide panel of odors and found similar ligand selectivity but dramatic differences in response magnitude. 87% of human-primate orthologs and 94% of mouse-rat orthologs showed differences in receptor potency (EC50) and/or efficacy (dynamic range) to an individual ligand. Notably dN/dS ratio, an indication of selective pressure during evolution, does not predict functional similarities between orthologs. Additionally, we found that orthologs responded to a common ligand 82% of the time, while human OR paralogs of the same subfamily responded to the common ligand only 33% of the time. Our results suggest that, while OR orthologs tend to show conserved ligand selectivity, their potency and/or efficacy dynamically change during evolution, even in closely related species. These functional changes in orthologs provide a platform for examining how the evolution of ORs can meet species-specific demands.
dc.format.extent e1002821 - ?
dc.language eng
dc.relation.ispartof PLoS Genet
dc.relation.isversionof 10.1371/journal.pgen.1002821
dc.subject Animals
dc.subject Evolution, Molecular
dc.subject Humans
dc.subject Ligands
dc.subject Macaca mulatta
dc.subject Mice
dc.subject Pan troglodytes
dc.subject Phylogeny
dc.subject Rats
dc.subject Receptors, Odorant
dc.subject Selection, Genetic
dc.subject Sensitivity and Specificity
dc.subject Sequence Homology, Amino Acid
dc.subject Species Specificity
dc.title Functional evolution of mammalian odorant receptors.
dc.type Journal Article
dc.department Genetics and Genomics en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/22807691
pubs.issue 7
pubs.organisational-group /Duke
pubs.organisational-group /Duke/Institutes and Provost's Academic Units
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers
pubs.organisational-group /Duke/Institutes and Provost's Academic Units/University Institutes and Centers/Duke Institute for Brain Sciences
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Molecular Genetics and Microbiology
pubs.organisational-group /Duke/School of Medicine/Basic Science Departments/Neurobiology
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Cancer Institute
pubs.publication-status Published
pubs.volume 8
dc.identifier.eissn 1553-7404

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