Olfactory receptor 2 in vascular macrophages drives atherosclerosis by NLRP3-dependent IL-1 production

Sniffing out atherosclerosis Olfactory receptors are best known for their presence in the nose and their role in detecting smells, but they are also present in other tissues and perform additional biological functions. For example, vascular macrophages involved in the pathogenesis of atherosclerosis express multiple subtypes of olfactory receptors. Orecchioni et al . focused on olfactory receptor 2, a receptor for the compound octanal, and identified its contribution to atherosclerosis pathogenesis and the formation of atherosclerotic plaques (see the Perspective by Rayner and Rasheed). The authors show that most of the octanal was not directly derived from the diet, but rather was generated as a by-product of lipid peroxidation, suggesting a potential pathway for intervention. —YN

Coevolution of the olfactory organ and its receptor repertoire in ray-finned fishes

Ray-finned fishes (Actinopterygii) perceive their environment through a range of sensory modalities, including olfaction 1,2. Anatomical diversity of the olfactory organ suggests that olfaction is differentially important among species 1,3,4. To explore this topic, we studied the evolutionary dynamics of the four main gene families (OR, TAAR, ORA/VR1 and OlfC/VR2) 5 coding for olfactory receptors in 185 species of ray-finned fishes. The large variation in the number of functional genes, between 28 in the Ocean Sunfish Mola mola and 1317 in the Reedfish Erpetoichthys calabaricus, is the result of parallel expansions and contractions of the four main gene families. Several ancient and independent simplifications of the olfactory organ are associated with massive gene losses. In contrast, polypteriforms, which have a unique and complex olfactory organ, have almost twice as many olfactory receptor genes as any other ray-finned fish. These observations suggest a functional link between morphology of the olfactory organ and richness of the olfactory receptor repertoire. Further, our results demonstrate that the genomic underpinning of olfaction in ray-finned fishes is heterogeneous and presents a dynamic pattern of evolutionary expansions, simplifications and reacquisitions.

Non-synaptic interactions between olfactory receptor neurons, a possible key feature of odor processing in flies

When flies explore their environment, they encounter odors in complex, highly intermittent plumes. To navigate a plume and, for example, find food, they must solve several challenges, including reliably identifying mixtures of odorants and their intensities, and discriminating odorant mixtures emanating from a single source from odorants emitted from separate sources and just mixing in the air. Lateral inhibition in the antennal lobe is commonly understood to help solving these challenges. With a computational model of the Drosophila olfactory system, we analyze the utility of an alternative mechanism for solving them: Non-synaptic (“ephaptic”) interactions (NSIs) between olfactory receptor neurons that are stereotypically co-housed in the same sensilla. We find that NSIs improve mixture ratio detection and plume structure sensing and do so more efficiently than the traditionally considered mechanism of lateral inhibition in the antennal lobe. The best performance is achieved when both mechanisms work in synergy. However, we also found that NSIs decrease the dynamic range of co-housed ORNs, especially when they have similar sensitivity to an odorant. These results shed light, from a functional perspective, on the role of NSIs, which are normally avoided between neurons, for instance by myelination.

Olfactory receptor subgenome and expression in a highly olfactory procellariiform seabird

Procellariiform seabirds rely on their sense of smell for foraging and homing. Both genomes and transcriptomes yield important clues about how olfactory receptor (OR) subgenomes are shaped by natural and sexual selection, yet no transcriptomes have been made of any olfactory epithelium of any bird species thus far. Here we assembled a high-quality genome and nasal epithelium transcriptome of the Leach’s storm-petrel (Oceanodroma leucorhoa) to extensively characterize their OR repertoire. Using a depth-of-coverage-assisted counting method, we estimated over 160 intact OR genes (∼500 including OR fragments). This method reveals the highest number of intact OR genes and the lowest proportion of pseudogenes compared to other waterbirds studied, and suggests that rates of OR gene duplication vary between major clades of birds, with particularly high rates in passerines. OR expression patterns reveal two OR genes (OR6-6 and OR5-11) highly expressed in adults, and four OR genes (OR14-14, OR14-12, OR10-2, and OR14-9) differentially expressed between age classes of storm-petrels. All four genes differentially expressed between age classes were more highly expressed in chicks compared to adults, suggesting that ORs genes may exhibit ontogenetic specializations. Three highly differentially expressed OR genes also had high copy number ratios, suggesting that expression variation may be linked to copy number in the genome. We provide better estimates of OR gene number by using a copy number-assisted counting method, and document ontogenetic changes in OR gene expression that may be linked to olfactory specialization. These results provide valuable insight into the expression, development, and macroevolution of olfaction in seabirds.

Transcriptional adaptation of sensory neurons to GPCR identity and activity

Sensory adaptation is critical to extract information from a changing world. Taking advantage of the extensive parallel coding lines present in the olfactory system, we explored the potential variations of neuronal identities before and after olfactory experience. We found that at rest, the transcriptomic profiles of olfactory sensory neuron populations are already highly divergent, specific to the olfactory receptor they express, and are surprisingly associated with the sequence of these latter. These divergent profiles further evolve in response to the environment, as odorant exposure leads to massive reprogramming via the modulation of transcription. Adenylyl cyclase 3, but not other main elements of the olfactory transduction cascade, plays a critical role in this activity-induced transcriptional adaptation. These findings highlight a broad range of sensory neuron identities that are present at rest and that adapt to the experience of the individual, thus providing a novel layer of complexity to sensory coding.

High Olfactory Receptor-Rich 11q11 Copy Number in Girls and African American Children

Copy number variants (CNVs) provide numerous genetic differences between individuals, and they have been linked with multiple human diseases. Obesity is one of the highly heritable complex disorders, which is associated with copy number variance (CNV). A recent report shows that the 11q11 gene, a novel olfactory receptor, and its copy number variants are involved in the early onset of obesity. In the current study, we analyzed the 11q11 gene copy number variance (CNV) based on gender in White/European American (EA) and African American (AA) normal weight and overweight/obese children. Sixty-nine boys and fifty-eight girls between the ages of 6 and 10 years belonging to either EA or AA ethnicity were involved in this study. As per World Health Organization (WHO) guidelines, each participant’s body weight and height were recorded. DNA was extracted from saliva, and the copy number variants for the 11q11 gene were measured using digital PCR. The descriptive analysis of the 11q11 copy number showed significantly more copies in girls compared to boys; similarly, AA participants had significantly increased CNV compared to EA. The normal weight (NW) and overweight/obese (OW/OB) girls were significantly less likely to belong to the low copy number variant (LCNV) group of 11q11 compared to boys; similarly, NW and OW/OB AA children were significantly less likely to belong to the LCNV group. The AA girls in LCNV had significantly higher BMI z-scores. Our findings suggest that the 11q11 copy number in children is race and gender-specific.