The missense of smell: functional variability in the human odorant receptor repertoire

Mainland, Joel D.; Keller, Andreas; Li, Yun R.; Zhou, Ting; Trimmer, Casey; Snyder, Lindsey L.; Moberly, Andrew H.; Adipietro, Kaylin A.; Liu, Wen Ling L; Zhuang, Huisheng; Zhan, Senmiao; Lee, Somin; Lin, Abigail; Matsunami, Hiroaki

doi:10.1038/nn.3598

Cited by 289 publications

(259 citation statements)

References 34 publications

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“…Another potential approach to find candidate pheromone molecules in the distant future could be based on identifying the ligands for human olfactory receptors (ORs) [85] that are highly conserved (in contrast to most human ORs which are highly variable between individuals [86,87]). Highly conserved ORs might result from strong stabilizing selection against mutations reducing sensitivity in pheromone-detecting ORs [5].…”

Section: (D) Methods For Narrowing Down the Candidate Molecules For Bmentioning

confidence: 99%

“…(Incidentally, receptors involved in detecting androstenone and androstadienone are among the ORs that are highly variable between individuals [88].) However, to-date few human ORs have been characterized and only approximately 10% have been linked to their ligands [85,86] so such an approach is currently hypothetical. In addition, some ORs might be highly conserved because they are also expressed in other tissues (e.g.…”

Section: (D) Methods For Narrowing Down the Candidate Molecules For Bmentioning

confidence: 99%

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The search for human pheromones: the lost decades and the necessity of returning to first principles

2015

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As humans are mammals, it is possible, perhaps even probable, that we have pheromones. However, there is no robust bioassay-led evidence for the widely published claims that four steroid molecules are human pheromones: androstenone, androstenol, androstadienone and estratetraenol. In the absence of sound reasons to test the molecules, positive results in studies need to be treated with scepticism as these are highly likely to be false positives. Common problems include small sample sizes, an overestimate of effect size (as no effect can be expected), positive publication bias and lack of replication. Instead, if we are to find human pheromones, we need to treat ourselves as if we were a newly discovered mammal, and use the rigorous methods already proven successful in pheromone research on other species. Establishing a pheromone relies on demonstration of an odour-mediated behavioural or physiological response, identification and synthesis of the bioactive molecule(s), followed by bioassay confirmation of activity. Likely sources include our sebaceous glands. Comparison of secretions from adult and pre-pubertal humans may highlight potential molecules involved in sexual behaviour. One of the most promising human pheromone leads is a nipple secretion from the areola glands produced by all lactating mothers, which stimulates suckling by any baby not just their own.

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Section: (D) Methods For Narrowing Down the Candidate Molecules For Bmentioning

confidence: 99%

Section: (D) Methods For Narrowing Down the Candidate Molecules For Bmentioning

confidence: 99%

The search for human pheromones: the lost decades and the necessity of returning to first principles

2015

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“…, χ 2 test) (Supplemental Table S20), which are known to be rapidly evolving between species (Mainland et al 2014). We also recovered genes corresponding to economically important traits that are valuable for future functional analyses and improvements of pig as an important livestock species, such as genes related to pork production (74 of 1515 fat deposition genes [Kunej et al 2013], or 4.88%) and disease resistance (76 of 1517 genes annotated with the GO: 0002376; immune system process, or 5.01%) (Supplemental Table S19).…”

Section: Recovery Of Missing Genesmentioning

confidence: 99%

Comprehensive variation discovery and recovery of missing sequence in the pig genome using multiple de novo assemblies

et al. 2016

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Uncovering genetic variation through resequencing is limited by the fact that only sequences with similarity to the reference genome are examined. Reference genomes are often incomplete and cannot represent the full range of genetic diversity as a result of geographical divergence and independent demographic events. To more comprehensively characterize genetic variation of pigs (Sus scrofa), we generated de novo assemblies of nine geographically and phenotypically representative pigs from Eurasia. By comparing them to the reference pig assembly, we uncovered a substantial number of novel SNPs and structural variants, as well as 137.02-Mb sequences harboring 1737 protein-coding genes that were absent in the reference assembly, revealing variants left by selection. Our results illustrate the power of whole-genome de novo sequencing relative to resequencing and provide valuable genetic resources that enable effective use of pigs in both agricultural production and biomedical research.

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“…Specific olfactory receptors are likely responsible for specific aspects of olfactory perception (4)(5)(6)(7). Because any two individuals differ by ∼30% of their olfactory receptor subtype genome (8), this renders a potentially unique nose for each person (4,9). If we could capture this uniqueness with a perceptual test, a sort of perceptual olfactory fingerprint, this should then be informative on the underlying individual olfactory receptor subtype genome.…”

mentioning

confidence: 99%

Individual olfactory perception reveals meaningful nonolfactory genetic information

Secundo

Snitz

Weissler

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Each person expresses a potentially unique subset of ∼400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the "olfactory fingerprint." Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10 −10 ), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10 −4 ), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10 −6 ). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.olfactory perception | HLA | MHC | olfactory genetics | autoimmunity H umans have superb olfactory discrimination (1, 2), likely reflecting the combined output of ∼400 different subtypes of olfactory receptors (3). Specific olfactory receptors are likely responsible for specific aspects of olfactory perception (4-7). Because any two individuals differ by ∼30% of their olfactory receptor subtype genome (8), this renders a potentially unique nose for each person (4, 9). If we could capture this uniqueness with a perceptual test, a sort of perceptual olfactory fingerprint, this should then be informative on the underlying individual olfactory receptor subtype genome. The notion of a psychophysical test informing on underlying genes is of course well known from vision, where color blindness charts inform us about genes coding for different opsins in the retina (10). In olfaction, specific anosmias can also point to alterations in a specific gene (4,11,12). Unlike in color vision or specific anosmias, the olfactory fingerprints we propose will likely not inform on a specific gene, but they may link overall perception to overall genetic makeup.Moreover, because the olfactory receptor genome is linked to various other genetic loci, this perceptual test may inform on genetic makeup beyond olfaction alone. For example, the olfactory receptor subtype genome is linked to MHC ge...

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The missense of smell: functional variability in the human odorant receptor repertoire

Cited by 289 publications

References 34 publications

The search for human pheromones: the lost decades and the necessity of returning to first principles

The search for human pheromones: the lost decades and the necessity of returning to first principles

Comprehensive variation discovery and recovery of missing sequence in the pig genome using multiple de novo assemblies

Individual olfactory perception reveals meaningful nonolfactory genetic information

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