Vertebrate-wide transcriptomic screening identifies immune cell-specific expression of the conserved OR-κ gene

Abstract Vertebrate chemoreceptor genes play a central role in detecting environmental chemical compounds through the olfactory organs and taste buds, enabling the perception of odors and tastants that are critical for survival. Through evolutionary processes, these genes have repeatedly undergone duplication, divergence, and pseudogenization, giving rise to lineage-specific gene repertoires that reflect ecological and behavioral adaptation. While the canonical functions of these chemoreceptors are confined to the nasal and oral cavities, accumulating evidence, particularly in mammals, indicates that some chemoreceptors are expressed and function in non-chemosensory (extra-nasal/oral) organs. However, such extra-nasal/oral expression has rarely been examined from a broad evolutionary perspective across vertebrate lineages. Here, we systematically investigated organ-wide expression patterns of chemoreceptor genes by conducting comprehensive bulk RNA-seq analysis across 13 organs in four representative species: mouse, Xenopus, Polypterus, and zebrafish. In all species, the majority (95–97%) of chemoreceptor genes were expressed in olfactory and gustatory organs, as expected. Remarkably, a subset (1–29%) showed expression in extra-nasal/oral organs, suggesting that such extra-nasal/oral expression may be a common phenomenon across vertebrates. In particular, the evolutionarily conserved OR-κ gene, with stable gene copy numbers, exhibited organ-independent expression across all analyzed species. Single-cell RNA-seq data further revealed that OR-κ is predominantly expressed in immune cells, implying potential function of chemoreception in immune systems. Furthermore, genomic context analysis showed that the OR-κ gene is isolated from canonical OR gene clusters, suggesting it may have distinct transcriptional regulatory mechanisms compared to typical olfactory receptors. Our findings expand the conventional view of chemoreceptors as sensory-specialized molecules, highlighting their unexpected functional diversity across vertebrate organs. Notably, the OR-κ gene appears to have an ancient evolutionary origin that likely traces back to the common ancestor of vertebrates. Taken together, this study provides us compelling evidence to reconsider the functions and evolutionary trajectories of chemoreceptor genes in vertebrates.