Genomics of selected human odorant receptors

Deciphering the relationship between molecules, olfactory receptors (ORs) and corresponding odors remains a challenging task. It requires a comprehensive identification of ORs responding to a given odorant. With the recent advances in artificial intelligence and the growing research in decoding the human olfactory perception from chemical features of odorant molecules, the applications of advanced machine learning have been revived. In this study, Convolutional Neural Network (CNN) and Graphical Convolutional Network (GCN) models have been developed on odorant molecules-odors and odorant molecules-olfactory receptors using a large set of 5955 molecules, 160 odors and 106 olfactory receptors. The performance of such models is promising with a Precision/Recall Area Under Curve of 0.66 for the odorant-odor and 0.91 for the odorant-olfactory receptor GCN models respectively. Furthermore, based on the correspondence of odors and ORs associated for a set of 389 compounds, an odor-olfactory receptor pairwise score was computed for each odor-OR combination allowing to suggest a combinatorial relationship between olfactory receptors and odors. Overall, this analysis demonstrate that artificial intelligence may pave the way in the identification of the smell perception and the full repertoire of receptors for a given odorant molecule.

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Application of artificial intelligence to decode the relationships between smell, olfactory receptors and small molecules

Achebouche

Tromelin

Audouze

et al. 2022

Sci Rep

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Human Male Superiority in Olfactory Sensitivity to the Sperm Attractant Odorant Bourgeonal

Olsson

Laska

2010

Chemical Senses

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Recent studies have shown that sperm chemotaxis critically involves the human olfactory receptor OR1D2, which is activated by the aromatic aldehyde bourgeonal. Given that both natural and sexual selection may act upon the expression of receptors, we hypothesized that human males are more sensitive than human females for bourgeonal. Using a 3-alternative forced-choice test procedure, olfactory detection thresholds were determined for a total of 500 subjects, 250 males, and 250 females between 18 and 40 years of age. We found that male subjects detected bourgeonal at significantly lower concentrations (mean value: 13 ppb) compared with female subjects (mean value: 26 ppb), whereas no such gender difference in olfactory sensitivity was found with helional, a structural analog of bourgeonal, and with n-pentyl acetate, an aliphatic ester, which were tested in parallel. Males and females did not differ in their frequency of specific anosmia for any of the 3 odorants. The frequency distributions of olfactory detection thresholds were monomodal with all 3 odorants in both genders. Olfactory detection thresholds did not differ significantly between pre- and postovulatory females with any of the 3 odorants. To the best of our knowledge, this is the first study ever to find a human male superiority in olfactory sensitivity. Single nucleotide polymorphisms and/or copy number variations in genes coding for olfactory receptors may be the proximate cause for our finding, whereas a gender difference in the behavioral relevance of bourgeonal may be the ultimate cause.

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Personal receptor repertoires: olfaction as a model

et al. 2012

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BackgroundInformation on nucleotide diversity along completely sequenced human genomes has increased tremendously over the last few years. This makes it possible to reassess the diversity status of distinct receptor proteins in different human individuals. To this end, we focused on the complete inventory of human olfactory receptor coding regions as a model for personal receptor repertoires.ResultsBy performing data-mining from public and private sources we scored genetic variations in 413 intact OR loci, for which one or more individuals had an intact open reading frame. Using 1000 Genomes Project haplotypes, we identified a total of 4069 full-length polypeptide variants encoded by these OR loci, average of ~10 per locus, constituting a lower limit for the effective human OR repertoire. Each individual is found to harbor as many as 600 OR allelic variants, ~50% higher than the locus count. Because OR neuronal expression is allelically excluded, this has direct effect on smell perception diversity of the species. We further identified 244 OR segregating pseudogenes (SPGs), loci showing both intact and pseudogene forms in the population, twenty-six of which are annotatively “resurrected” from a pseudogene status in the reference genome. Using a custom SNP microarray we validated 150 SPGs in a cohort of 468 individuals, with every individual genome averaging 36 disrupted sequence variations, 15 in homozygote form. Finally, we generated a multi-source compendium of 63 OR loci harboring deletion Copy Number Variations (CNVs). Our combined data suggest that 271 of the 413 intact OR loci (66%) are affected by nonfunctional SNPs/indels and/or CNVs.ConclusionsThese results portray a case of unusually high genetic diversity, and suggest that individual humans have a highly personalized inventory of functional olfactory receptors, a conclusion that might apply to other receptor multigene families.

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Genomics of selected human odorant receptors

Cited by 3 publications

References 32 publications

Application of artificial intelligence to decode the relationships between smell, olfactory receptors and small molecules

Application of artificial intelligence to decode the relationships between smell, olfactory receptors and small molecules

Human Male Superiority in Olfactory Sensitivity to the Sperm Attractant Odorant Bourgeonal

Personal receptor repertoires: olfaction as a model

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