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A natural polymorphism alters odour and DEET sensitivity in an insect odorant receptor


Blood-feeding insects such as mosquitoes are efficient vectors of human infectious diseases because they are strongly attracted by body heat, carbon dioxide and odours produced by their vertebrate hosts. Insect repellents containing DEET (N,N-diethyl-meta-toluamide) are highly effective, but the mechanism by which this chemical wards off biting insects remains controversial despite decades of investigation1,2,3,4,5,6,7,8,9,10,11. DEET seems to act both at close range as a contact chemorepellent, by affecting insect gustatory receptors12, and at long range, by affecting the olfactory system1,2,3,4,5,6,7,8,9,10,11. Two opposing mechanisms for the observed behavioural effects of DEET in the gas phase have been proposed: that DEET interferes with the olfactory system to block host odour recognition1,2,3,4,5,6,7 and that DEET actively repels insects by activating olfactory neurons that elicit avoidance behaviour8,9,10,11. Here we show that DEET functions as a modulator of the odour-gated ion channel formed by the insect odorant receptor complex13,14. The functional insect odorant receptor complex consists of a common co-receptor, ORCO (ref. 15) (formerly called OR83B; ref. 16), and one or more variable odorant receptor subunits that confer odour selectivity17. DEET acts on this complex to potentiate or inhibit odour-evoked activity or to inhibit odour-evoked suppression of spontaneous activity. This modulation depends on the specific odorant receptor and the concentration and identity of the odour ligand. We identify a single amino-acid polymorphism in the second transmembrane domain of receptor OR59B in a Drosophila melanogaster strain from Brazil that renders OR59B insensitive to inhibition by the odour ligand and modulation by DEET. Our data indicate that natural variation can modify the sensitivity of an odour-specific insect odorant receptor to odour ligands and DEET. Furthermore, they support the hypothesis that DEET acts as a molecular ‘confusant’ that scrambles the insect odour code, and provide a compelling explanation for the broad-spectrum efficacy of DEET against multiple insect species.

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Figure 1: DEET scrambles the Drosophila odour code.
Figure 2: OR59B–ORCO sensitivity to DEET varies across wild-type D. melanogaster strains.
Figure 3: OR59B–ORCO neurons in the Boa Esperança strain are insensitive to modulation by DEET.
Figure 4: A single natural polymorphism in OR59B confers insensitivity to DEET.

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We thank C. Bargmann, K. Lee, K. Scott, L. Stowers and members of the Vosshall lab for discussion and comments on the manuscript; and K. Weniger for technical assistance with the SPME and GC–MS experiments. This work was funded in part by a grant to R. Axel and L.B.V. from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative and by a grant to L.B.V. from the NIH (RO1 DC008600). L.B.V. is an investigator of the Howard Hughes Medical Institute. M.C.S. and B.S.H. are supported by the Max Planck Society.

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Authors and Affiliations



M.P. carried out all the experiments and analysed the data. N.S. contributed to sequencing Or59b in the 19 strains and generated the Or59b mutants. M.C.S. and B.S.H. designed and supervised the SPME collections and GC–MS analysis in Fig. 1a. M.P. and L.B.V. together designed the experiments, interpreted the results, produced the figures and wrote the paper.

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Correspondence to Leslie B. Vosshall.

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The authors declare no competing financial interests.

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Pellegrino, M., Steinbach, N., Stensmyr, M. et al. A natural polymorphism alters odour and DEET sensitivity in an insect odorant receptor. Nature 478, 511–514 (2011).

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