Abstract

BackgroundAll living things speak chemical. The challenge is to discover the vocabulary, the volatile odorant chemicals that enable communication across phylogenies and to translate them to physiological, behavioural and ecological function. Olfactory receptors (ORs) interface animals with airborne odorants. Expression of single ORs in human embryonic kidney cells (HEK-293) makes it possible to interrogate ORs with synthetic chemicals and to identify cognate ligands that convey olfactory information. ResultsThe cosmopolitan strain of the vinegar fly Drosophila melanogaster has accompanied the human expansion out of Africa, more than ten thousand years ago. These flies are strictly anthropophilic and depend on human resources and housing for survival, particularly in colder climate zones. Curiously, humans sense the scent of a single fly, and more precisely the female pheromone (Z)-4 undecenal (Z4-11Al), at 10 ng/mL (0.06 {micro}mol/L). A screening of all functional human ORs in a HEK-293 assay provides an explanation for this astounding sensitivity, as it shows that OR10A6, one of the most highly expressed human ORs, is specifically tuned to Z4-11Al. Chemical analysis of fly effluvia confirms that cosmopolitan D. melanogaster females release Z4-11Al, while females of an African fly strain from Zimbabwe release a 1:3-blend of Z4-11Al and (Z)-4 nonenal (Z4-9Al). Interestingly, a blend of Z4-9Al and Z4-11Al produces a different aroma than the the single compounds, which is why we readily differentiate cosmopolitan and Zimbabwe flies by nose. ConclusionThat we sensitively and specifically perceive the fly pheromone Z4-11Al suggests that it is a component of human odour scenes. This may have afforded a sensory drive during adaptation of commensal flies to human habitats and selected for a role of Z4-11Al in fly aggregation and premating communication. Screening ORs for key ligands leads to the discovery of messenger chemicals that enable chemical communication among and betwen vertebrate and invertebrate animals.