Molecular basis for odorant receptor tuning: a short C-terminal sequence is necessary and sufficient for selectivity of mosquito Or8.

A birth-and-death evolutionary model for odorant receptor gene repertoires presumes the creation of repertoires with the capacity for high-level diversity and rapid ligand specificity change. This changes the recognised odour space, directly affecting fitness-related behaviours and ultimately affecting adaptation to new environments and resources. The proximate molecular mechanisms underlying the tuning of odorant receptor repertoires, and thus peripheral olfaction, are unclear. In the present study, we report a concrete example of this model of odorant receptor evolution leading to rapid changes in receptor tuning that leave the peripheral neuronal circuitry intact. We identified a conserved odorant receptor gene in mosquitoes, Or8, which in Culex quinquefasciatus underwent a duplication and inversion event. The paralogues differ in only minor structural changes manifesting at the C-terminus. We assessed the specificity of the paralogous odorant receptors and receptor neurones. We found that the functional tuning of the receptor was indeed reflected in minor differences in amino acid structure. Specifically, we found that enantiomeric specificity of these mosquito Or8 paralogues relies on eight C-terminal amino acids encoded in the final exon of the gene; thus, the birth of a paralogous odorant receptor can change the tuning of the peripheral olfactory system.