Class-wide sequence, structural, and docking-profile diversity of insect odorant receptors and structural specialization of Orco

Abstract

Insect olfaction is facilitated by a heterotetrameric odorant receptor-odorant receptor co-receptor (OR-Orco) complex, which is distinct from that of vertebrate ORs. However, extensive sequence divergence and lineage-specific expansion have complicated large-scale comparisons of OR repertoires across insects. Here, we integrated sequence similarity, structural similarity, and molecular docking to analyze ORs from 115 insect species. Across this class-wide sampling, OR repertoire size was associated with adult diet, larval diet, and habitat, but not with circadian rhythm. We developed a "trunk-branch" network framework to classify ORs according to sequence and structural similarity and used large-scale molecular docking to derive comparative docking profiles. Despite marked differences in sequence- and structural-community composition, almost all sampled orders contained ORs assigned to all six docking-profile communities. Holometabolous insects showed higher OR sequence-community diversity than non-holometabolous insects, and docking-profile composition differed between extant lineages whose order-level origins predate or postdate the end-Permian mass extinction. Most notably, we identified a highly conserved extracellular {beta}-sheet in Orco that restricts ligand access to the binding pocket and may contribute to its reduced capacity to bind natural odorants. The emergence of Orco represents a key evolutionary transition from homomeric receptors to heteromeric OR-Orco complexes, and our results suggest that this transition may have been accompanied by pronounced specialization of the extracellular domain and binding pocket. Together, these analyses provide a class-wide framework for comparing insect OR diversity and generate testable hypotheses for future experimental and evolutionary studies.