From musk to body odor: Decoding olfaction through genetic variation
Li, Bingjie; Kamarck, Marissa L; Peng, Qianqian; Lim, Fei-Ling; Keller, Andreas; Smeets, Monique A M; Mainland, Joel D; Wang, Sijia
(2022) PLoS Genetics, volume 18, issue 2, pp. 1 - 27
(Article)
Abstract
The olfactory system combines input from multiple receptor types to represent odor information, but there are few explicit examples relating olfactory receptor (OR) activity patterns to odor perception. To uncover these relationships, we performed genome-wide scans on odor-perception phenotypes for ten odors in 1000 Han Chinese and validated results for
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six of these odors in an ethnically diverse population (n = 364). In both populations, consistent with previous studies, we replicated three previously reported associations (β-ionone/OR5A1, androstenone/OR7D4, cis-3-hexen-1-ol/OR2J3 LD-band), but not for odors containing aldehydes, suggesting that olfactory phenotype/genotype studies are robust across populations. Two novel associations between an OR and odor perception contribute to our understanding of olfactory coding. First, we found a SNP in OR51B2 that associated with trans-3-methyl-2-hexenoic acid, a key component of human underarm odor. Second, we found two linked SNPs associated with the musk Galaxolide in a novel musk receptor, OR4D6, which is also the first human OR shown to drive specific anosmia to a musk compound. We noticed that SNPs detected for odor intensity were enriched with amino acid substitutions, implying functional changes of odor receptors. Furthermore, we also found that the derived alleles of the SNPs tend to be associated with reduced odor intensity, supporting the hypothesis that the primate olfactory gene repertoire has degenerated over time. This study provides information about coding for human body odor, and gives us insight into broader mechanisms of olfactory coding, such as how differential OR activation can converge on a similar percept.
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Keywords: Ecology, Evolution, Behavior and Systematics, Molecular Biology, Genetics, Genetics(clinical), Cancer Research
ISSN: 1553-7390
Publisher: Public Library of Science
Note: Funding Information: Funding:ThisworkwassupportedbytheStrategic PriorityResearchProgram(GrantNo. XDB38020400),theNationalKeyResearchand DevelopmentProject(GrantNo. 2018YFC0910403),theNationalNaturalScience FoundationofChina(GrantNo.91631307), ShanghaiMunicipalScienceandTechnologyMajor Project(GrantNo.2017SHZDZX01)toSW,CAS YouthInnovationPromotionAssociation(Grant No.2020276)toQP,theNationalInstitutesof Health(GrantR01DC013339)toJDM,andinpart bytheNationalCenterforAdvancingTranslational SciencesClinicalandTranslationalScienceAward program(grantUL1TR000043)toAK.Aportionof thework(validationstudy)wasperformedatthe MonellChemosensoryReceptorSignalingCore, whichwassupportedinpartbytheNational InstituteonDeafnessandOtherCommunication Disorders(CoreGrantP30DC011735)toJDM. ThediscoverystudywasfundedinpartbyUnilever R&D(theNetherlands)toSW.Unileveremployees M.A.M.S.andF.-L.L.areco-authorswho contributedinstudyconceptualizationandwriting (review&editing).M.A.M.S.alsoprovided resources(odorsticksforthediscoverystudy). Otherfundershadnoroleinstudydesign,data collectionandanalysis,decisiontopublish,or preparationofthemanuscript. Funding Information: Funding: This work was supported by the Strategic Priority Research Program (Grant No. XDB38020400), the National Key Research and Development Project (Grant No. 2018YFC0910403), the National Natural Science Foundation of China (Grant No. 91631307), Shanghai Municipal Science and Technology Major Project (Grant No.2017SHZDZX01) to SW, CAS Youth Innovation Promotion Association (Grant No. 2020276) to QP, the National Institutes of Health (Grant R01 DC013339) to JDM, and in part by the National Center for Advancing Translational Sciences Clinical and Translational Science Award program (grant UL1 TR000043) to AK. A portion of the work (validation study) was performed at the Monell Chemosensory Receptor Signaling Core, which was supported in part by the National Institute on Deafness and Other Communication Disorders (Core Grant P30 DC011735) to JDM. The discovery study was funded in part by Unilever R&D (the Netherlands) to SW. Unilever employees M.A.M.S. and F.-L.L. are co-authors who contributed in study conceptualization and writing (review & editing). M.A.M.S. also provided resources (odor sticks for the discovery study). Other funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: 2022 Li et al.
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