Allelic variation at 4 loci in the human olfactory receptor gene OR7D4 is associated with perceptual variation in the sex steroid-derived odorants, androstenone, and androstadienone. Androstadienone has been linked with chemosensory identification whereas androstenone makes pork from uncastrated pigs distasteful ("boar taint"). In a sample of 2224 individuals from 43 populations, we identified 45 OR7D4 single nucleotide polymorphisms. Coalescent modeling of frequency-site-spectrum-based statistics identified significant deviation from neutrality in human OR7D4; individual populations with statistically significant deviations from neutrality include Gujarati, Beijing Han, Great Britain, Iberia, and Puerto Rico. Analysis of molecular variation values indicated statistically significant population differentiation driven mainly by the 4 alleles associated with androstenone perception variation; however, fixation values were low suggesting that genetic structure may not have played a strong role in creating these group divisions. We also studied OR7D4 in the genomes of extinct members of the human lineage: Altai Neandertal and Denisovan. No variants were identified in Altai but 2 were in Denisova, one of which is shared by modern humans and one of which is novel. A functional test of modern human and a synthesized mutant Denisova OR7D4 indicated no statistically significant difference in responses to androstenone between the 2 species. Our results suggest non-neutral evolution for an olfactory receptor gene.
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http://dx.doi.org/10.1093/chemse/bjv030 | DOI Listing |
Front Mol Biosci
January 2025
Medical Laboratory, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, China.
Olfactory receptors, classified as G-protein coupled receptors (GPCRs), have been a subject of scientific inquiry since the early 1950s. Historically, investigations into the sensory mechanisms of olfactory receptors were often confined to behavioral characteristics in model organisms or the expression of related proteins and genes. However, with the development of cryo-electron microscopy techniques, it has gradually become possible to decipher the specific structures of olfactory receptors in insects and humans.
View Article and Find Full Text PDFFunction (Oxf)
January 2025
Institute for Integrative Physiology, Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL. 60637, USA.
Patients with obstructive sleep apnea (OSA) experience chronic intermittent hypoxia (CIH). OSA patients and CIH-treated rodents exhibit overactive sympathetic nervous system and hypertension, mediated through hyperactive carotid body (CB) chemoreflex. Activation of olfactory receptor 78 (Olfr78) by hydrogen sulfide (H2S) is implicated in CB activation and sympathetic nerve responses to CIH, but the downstream signaling pathways remain unknown.
View Article and Find Full Text PDFJ Physiol Sci
January 2025
Department of Autonomic Neuroscience, Tokyo Metropolitan Institute for Geriatrics and Gerontology, 35-2 Sakaecho, Itabashi-ku, 173-0015, Tokyo, Japan.
The olfactory bulb receives cholinergic basal forebrain inputs as does the neocortex. With a focus on nicotinic acetylcholine receptors (nAChRs), this review article provides an overview and discussion of the following findings: (1) the nAChRs-mediated regulation of regional blood flow in the neocortex and olfactory bulb, (2) the nAChR subtypes that mediate their responses, and (3) their activity in old rats. The activation of the α4β2-like subtype of nAChRs produces vasodilation in the neocortex, and potentiates olfactory bulb vasodilation induced by olfactory stimulation.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Boston, MA, 02134, USA.
Natural olfactory systems possess remarkable sensitivity and precision beyond what is currently achievable by engineered gas sensors. Unlike their artificial counterparts, noses are capable of distinguishing scents associated with mixtures of volatile molecules in complex, typically fluctuating environments and can adapt to changes. This perspective examines the multifaceted biological principles that provide olfactory systems their discriminatory prowess, and how these ideas can be ported to the design of electronic noses for substantial improvements in performance across metrics such as sensitivity and ability to speciate chemical mixtures.
View Article and Find Full Text PDFFront Physiol
January 2025
Plant Protection Institute, Hebei Academy of Agriculture and Forestry Sciences, Key Laboratory of Integrated Pest Management on Crops in Northern Region of North China, Ministry of Agriculture and Rural Affairs, IPM Innovation Center of Hebei Province, International Science and Technology Joint Research Center on IPM of Hebei Province, Baoding, China.
Background: (Fabricius) (Hemiptera: Alydidae) is a major soybean pest throughout East Asia that relies on its advanced olfactory system for the perception of plant-derived volatile compounds and aggregation pheromones for conspecific and host plant localization. Odorant binding proteins (OBPs) facilitate the transport of odorant compounds across the sensillum lymph within the insect olfactory system, enabling their interaction with odorant receptors (ORs).
Methods: Real-time quantitative PCR (qRT-PCR) analyses, fluorescence-based competitive binding assays, and molecular docking analyses were applied to assess the expression and ligand-binding properties of OBP38 from .
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