title: Global Survey of Variation in a Human Olfactory Receptor Gene Reveals Signatures of Non-Neutral Evolution.
abstract: Allelic variation at 4 loci in the human olfactory receptor gene OR7D4 is associated with perceptual variation in the sex steroid-derived odorants, androstenone, and androstadienone. Androstadienone has been linked with chemosensory identification whereas androstenone makes pork from uncastrated pigs distasteful ("boar taint"). In a sample of 2224 individuals from 43 populations, we identified 45 OR7D4 single nucleotide polymorphisms. Coalescent modeling of frequency-site-spectrum-based statistics identified significant deviation from neutrality in human OR7D4; individual populations with statistically significant deviations from neutrality include Gujarati, Beijing Han, Great Britain, Iberia, and Puerto Rico. Analysis of molecular variation values indicated statistically significant population differentiation driven mainly by the 4 alleles associated with androstenone perception variation; however, fixation values were low suggesting that genetic structure may not have played a strong role in creating these group divisions. We also studied OR7D4 in the genomes of extinct members of the human lineage: Altai Neandertal and Denisovan. No variants were identified in Altai but 2 were in Denisova, one of which is shared by modern humans and one of which is novel. A functional test of modern human and a synthesized mutant Denisova OR7D4 indicated no statistically significant difference in responses to androstenone between the 2 species. Our results suggest non-neutral evolution for an olfactory receptor gene.
authors.affiliation: Department of Anthropology, POB 757720, University of Alaska Fairbanks, Fairbanks, AK 99775, USA, Department of Chemistry and Biochemistry, 900 Yukon Drive, University of Alaska Fairbanks, Fairbanks, AK 99775, USA, kchoover@alaska.edu.
authors.forename: Kara C
authors.initials: KC
authors.lastname: Hoover
authors.affiliation: Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Omer
authors.initials: O
authors.lastname: Gokcumen
authors.affiliation: Department of Molecular Genetics and Microbiology, 264 CARL Building, Box 3509 Duke University Medical Center, Durham, NC 27710, USA and.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Qureshy
authors.affiliation: Department of Molecular Genetics and Microbiology, 264 CARL Building, Box 3509 Duke University Medical Center, Durham, NC 27710, USA and.
authors.forename: Elise
authors.initials: E
authors.lastname: Bruguera
authors.affiliation: Department of Molecular Genetics and Microbiology, 264 CARL Building, Box 3509 Duke University Medical Center, Durham, NC 27710, USA and.
authors.forename: Aulaphan
authors.initials: A
authors.lastname: Savangsuksa
authors.affiliation: Faculty of Life Sciences, The University of Manchester, Oxford Road, Manchester, M13 9PL, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Cobb
authors.affiliation: Department of Molecular Genetics and Microbiology, 264 CARL Building, Box 3509 Duke University Medical Center, Durham, NC 27710, USA and.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsunami
mesh_terms: D000483:Alleles; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D019143:Evolution, Molecular; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018035:Receptors, Odorant / Q000235:genetics*
chemical_list: D018035:Receptors, Odorant; D004247:DNA
keywords: Altai Neandertal; Denisova; OR7D4; androstenone perception; human variation; selection