African Gene Flow Reduces Beta-Ionone Anosmia/Hyposmia Prevalence in Admixed Malagasy Populations

While recent advances in genetics make it possible to follow the genetic exchanges between populations and their phenotypic consequences, the impact of the genetic exchanges on the sensory perception of populations has yet to be explored. From this perspective, the present study investigated the consequences of African gene flow on odor perception in a Malagasy population with a predominantly East Asian genetic background. To this end, we combined psychophysical tests with genotype data of 235 individuals who were asked to smell the odorant molecule beta-ionone (βI). Results showed that in this population the ancestry of the OR5A1 gene significantly influences the ability to detect βI. At the individual level, African ancestry significantly protects against specific anosmia/hyposmia due to the higher frequency of the functional gene (OR ratios = 14, CI: 1.8–110, p-value = 0.012). At the population level, African introgression decreased the prevalence of specific anosmia/hyposmia to this odorous compound. Taken together, these findings validate the conjecture that in addition to cultural exchanges, genetic transfer may also influence the sensory perception of the population in contact.

Genetic and functional odorant receptor variation in the Homo lineage

The largest and rapidly evolving gene family of odorant receptors detect odors to variable degrees due to amino acid sequence and protein structure. Hybridization between humans, Neandertals, and Denisovans implies shared behavior1,2, although some speculate that Neandertals were poor smellers 3,4. We identified genetic and functional variation in humans and extinct lineages in 30 receptors with known function. We show that structural changes in receptor proteins altered odor sensitivity not specificity, indicating a common repertoire across lineages. In humans, variation in receptors may change odor perception or induce odor-specific anosmia 5,6. Variation in sensitivity may reflect local adaptations (e.g., Denisovan sensitivity to honey, Neandertals sensitivity to grass and sulphur). Extinct human lineages had highly conserved receptor genes and proteins. We observe a similar pattern in the Neandertal OR5P3 variant, which produced no response to ∼350 odors. Our data suggest that receptor structure was highly conserved in our closest relatives, but not in living humans. The diversity of geographic adaptations in humans may have produced greater functional variation, increasing our olfactory repertoire and expanding our adaptive capacity 5. Our results provide insight into odorant receptor function and shed light on the olfactory ecology of ancient humans and their extinct relatives. By studying the function of ancient odorant receptor genes, we have been able to get a glimpse of the sensory world of our extinct ancestors and relatives, with some of the variants giving specific insights into potential adaptations shown by these long-dead populations. The functional variability we have identified in the molecular structure of the odorant receptor proteins will aid in the more general problem of understanding the function of odorant receptor proteins and the neurons they are carried by, opening the road to linking receptor function to perception.

Blindness, But Not HMHA Anosmia, Predicts Loneliness: A Psychophysical Study

Olfactory deficits can play a detrimental role in everyday social functioning. Perception of 3-hydroxy-3-methylhexanoic acid (HMHA)—a body odor component—could also be linked to this research area. However, no study so far has addressed the problem of HMHA perception in the context of the previously reported relationship between olfactory abilities and social difficulties. Here, we tested whether HMHA-specific anosmia predicted loneliness understood both as a cognitive evaluation of social participation and as one’s social isolation, and we additionally analyzed the effects and correlates of HMHA perception in relation to sightedness. The study comprised 196 people, of whom 99 were blind. We found that subjects with blindness declared particularly high loneliness, but HMHA anosmia and the interaction of sightedness and HMHA anosmia predicted neither loneliness nor social withdrawal. In addition, HMHA pleasantness was positively associated with social withdrawal of the subjects with blindness and emotional loneliness correlated with HMHA familiarity regardless of sightedness.

From musk to body odor: decoding olfaction through genetic variation

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 1003 Han Chinese and validated results for six of these odors in an ethnically diverse population (n=364). In both populations, we replicated three previously reported associations (β-ionone/OR5A, androstenone/OR7D4, cis-3-hexen-1-ol/OR2J3 LD-band), 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 OR shown to drive specific anosmia to a musk compound. We also found that the derived alleles of the SNPs reportedly associated with odor perception tend to reduce 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.

Individual Differences in Thresholds and Consumer Preferences for Rotundone Added to Red Wine

Rotundone is an aromatic compound found in the skin of some grapes (e.g., Shiraz, Noiret) that contributes peppery notes to wines made with these varieties. There may be a specific anosmia for rotundone, as some individuals are unable to detect it even at high concentrations, despite otherwise normal olfaction. This may affect perception of and preference for rotundone-containing wines. Here, we report rotundone detection thresholds (orthonasal n = 56; retronasal n = 53) and rejection thresholds (n = 86) in red wine for a convenience sample of non-expert consumers in Pennsylvania. Focus groups were conducted to better understand consumer attitudes and preferences for rotundone. Ortho- and retronasal detection thresholds were nearly identical (140 v. 146 ng/L). Roughly 40% of our sample was anosmic to rotundone, extending evidence for a specific anosmia to a North American cohort. As ortho- and retronasal thresholds were extremely similar, future work on rotundone can rely on orthonasal assessment. In our participants, added rotundone was generally disliked, and in focus groups, the concept of a ‘peppery’ wine was not appealing. Winemakers need to carefully consider biological and attitudinal segmentation when making and marketing peppery wines. Further work is needed to identify the genetic basis for this anosmia.

Specific anosmia in humans and animals: Environmental and genetic influences

Olfaction plays a very important role across the lifespan of most mammalian species, including humans. Being the oldest, chemical communication is one of the least understood forms of communication due in part to the difficulty of detecting and measuring the chemicals in a sample. The ability to detect chemicals in the environment serves many functions. Individuals with specific anosmia, or “odor blindness”, have significantly increased olfactory thresholds to particular odorants though they show normal general olfactory acuity. Hereby we review research on specific anosmia in humans, factors that may affect individual variation in olfaction as well as animal models of specific anosmia. Variability in sensitivity to odorants is influenced by genotype, age, gender, individual olfactory experience and environmental cues. Large data pile from human and animal studies suggests that not all factors are determined yet. The possibility of induction of olfactory sensitivity to biologically relevant chemical cues is discussed. Olfactory plasticity determines the adaptability of the species to the environment. Mechanisms that underlie the induction of sensitivity to the odorants still to be elucidated.