Molecular evolution of octopamine receptors in Drosophila

Octopamine (OA), the insect analog of noradrenaline, plays important roles in diverse behavioral and physiological processes, from modulating fight-or-flight behavior to regulating post-mating ovulation. In Drosophila, six OA receptors have been identified: Oamb, Octα2R, Octβ1R, Octβ2R, Octβ3R, and Oct-TyrR, and they have been linked to different behavioral and physiological processes. Here, we investigated the evolutionary characteristics of these receptors across Drosophila species. We found that OA receptors are generally found as single-copy genes. Notably, Octβ2R and Octβ3R exhibit positive selection within the melanogaster group, though in different structural regions from one another. The positively selected sites in Octβ2R are exclusively located in regions important for ligand binding, whereas those in Octβ3R are predominantly found in regions crucial for signal transduction. Interestingly, Octβ2R remains highly conserved outside the melanogaster group, so the detection of positive selection in its ligand-binding related domains within this clade raises the possibility that it has evolved an additional, melanogaster-specific ligand interaction(s), among other potential reasons. These findings highlight the evolutionary flexibility of aminergic signaling and suggest lineage-specific adaptations of OA receptor function in Drosophila, likely shaped by lineage-specific selective pressures.