From musk to body odor: Decoding olfaction through genetic variation.

Bingjie Li,Qianqian Peng,Sijia Wang,Monique A M Smeets,Fei-Ling Lim,Joel D Mainland,Andreas Keller,Marissa L Kamarck,Sarah Markt

doi:10.1371/journal.pgen.1009564

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 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.

Highlights

Every individual experiences smell in their own unique way–variation in odor perception can range from specific anosmias, where an individual completely lacks the ability to perceive a particular odorous compound, to differences in individual experience of quality, pleasantness, and/ or intensity of odors [1]
We found that the derived alleles of the single nucleotide polymorphisms (SNPs) tend to be associated with reduced odor intensity, supporting the hypothesis that the primate olfactory gene repertoire has degenerated over time
Genetic diversity in the olfactory receptor repertoire contributes to variation in odor perception, we have few explicit predictions relating variation in a specific Olfactory receptors (ORs) to perception

Summary

Introduction

Every individual experiences smell in their own unique way–variation in odor perception can range from specific anosmias, where an individual completely lacks the ability to perceive a particular odorous compound, to differences in individual experience of quality, pleasantness, and/ or intensity of odors [1]. Comparing this perceptual variability with genetic variability allows us to identify the role of single odorant receptors in the perceptual code. Even within the set of intact genes, a genetic variant can alter function of a single OR and thereby alter perception of an odor. There are 15 cases where perceptual variability of an odor correlated with a genetic variant in a receptor that responds to the odor in a cell-based assay [5,6,7,8,9,10,11,12], and 13 further cases with strong genetic evidence, but no supporting evidence from cell-based assays [10,11,13]

Methods

Results

Discussion

Conclusion