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Functional Evolution of Mammalian Odorant Receptors 英文参考文献.doc

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Functional Evolution of Mammalian Odorant Receptors 英文参考文献

FunctionalEvolutionofMammalianOdorantReceptors KaylinA.Adipietro1,JoelD.Mainland1¤,HiroakiMatsunami1,2* 1DepartmentofMolecularGeneticsandMicrobiology,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica,2DepartmentofNeurobiology andDukeInstituteforBrainSciences,DukeUniversityMedicalCenter,Durham,NorthCarolina,UnitedStatesofAmerica 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,functionalassessmentofORsinrelatedspeciesremainslargelyuntested.Hereweinvestigatedthe 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 chimpanzeeandrhesusmacaqueand17mouse-ratorthologouspairsthatarebroadlyrepresentativeoftheORrepertoire. WefunctionallycharacterizedtheinvitroresponsesofORstoawidepanelofodorsandfoundsimilarligandselectivitybut dramatic differencesin responsemagnitude.87% ofhuman-primateorthologs and94% ofmouse-ratorthologs showed differences in receptor potency (EC50) and/or efficacy (dynamic range) to an individual ligand. Notably dN/dS ratio, an indicationofselectivepressureduringevolution,doesnotpredictfunctionalsimilaritiesbetweenorthologs.Additionally, wefoundthatorthologsrespondedtoacommonligand82%ofthetime,whilehumanORparalogsofthesamesubfamily 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-specificdemands. Citation: Adipietro KA, Mainland JD, Matsunami H (2012) Functional E