Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Odorant reception in the malaria mosquito Anopheles gambiae

Abstract

The mosquito Anopheles gambiae is the major vector of malaria in sub-Saharan Africa. It locates its human hosts primarily through olfaction, but little is known about the molecular basis of this process. Here we functionally characterize the Anopheles gambiae odorant receptor (AgOr) repertoire. We identify receptors that respond strongly to components of human odour and that may act in the process of human recognition. Some of these receptors are narrowly tuned, and some salient odorants elicit strong responses from only one or a few receptors, suggesting a central role for specific transmission channels in human host-seeking behaviour. This analysis of the Anopheles gambiae receptors permits a comparison with the corresponding Drosophila melanogaster odorant receptor repertoire. We find that odorants are differentially encoded by the two species in ways consistent with their ecological needs. Our analysis of the Anopheles gambiae repertoire identifies receptors that may be useful targets for controlling the transmission of malaria.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Functional characterization of the AgOrs.
Figure 2: Tuning breadths of receptors.
Figure 3: Odorant tuning curves.
Figure 4: Distribution of responses across a physicochemical odour space.
Figure 5: Distribution of odorants in a receptor activity-based odour space.

Similar content being viewed by others

References

  1. World Health Organization. World Malaria Report 〈http://www.who.int/malaria/publications/atoz/9789241563697/en/index.html〉 (2008)

  2. Zwiebel, L. J. & Takken, W. Olfactory regulation of mosquito-host interactions. Insect Biochem. Mol. Biol. 34, 645–652 (2004)

    Article  CAS  Google Scholar 

  3. Takken, W. The role of olfaction in host-seeking of mosquitos: a review. Insect Sci. Applic. 12, 287–295 (1991)

    Google Scholar 

  4. Takken, W. & Knols, B. G. J. Odor-mediated behavior of Afrotropical malaria mosquitoes. Annu. Rev. Entomol. 44, 131–157 (1999)

    Article  CAS  Google Scholar 

  5. Su, C. Y., Menuz, K. & Carlson, J. R. Olfactory perception: receptors, cells, and circuits. Cell 139, 45–59 (2009)

    Article  CAS  Google Scholar 

  6. Hill, C. A. et al. G protein coupled receptors in Anopheles gambiae . Science 298, 176–178 (2002)

    Article  ADS  CAS  Google Scholar 

  7. Fox, A. N., Pitts, R. J., Robertson, H. M., Carlson, J. R. & Zwiebel, L. J. Candidate odorant receptors from the malaria vector mosquito Anopheles gambiae and evidence of down-regulation in response to blood feeding. Proc. Natl Acad. Sci. USA 98, 14693–14697 (2001)

    Article  ADS  CAS  Google Scholar 

  8. Hallem, E. A., Fox, A. N., Zwiebel, L. J. & Carlson, J. R. Olfaction: mosquito receptor for human-sweat odorant. Nature 427, 212–213 (2004)

    Article  ADS  CAS  Google Scholar 

  9. Dobritsa, A. A., van der Goes van Naters, W., Warr, C. G., Steinbrecht, R. A. & Carlson, J. R. Integrating the molecular and cellular basis of odor coding in the Drosophila antenna. Neuron 37, 827–841 (2003)

    Article  CAS  Google Scholar 

  10. Kreher, S. A., Mathew, D., Kim, J. & Carlson, J. R. Translation of sensory input into behavioral output via an olfactory system. Neuron 59, 110–124 (2008)

    Article  CAS  Google Scholar 

  11. Hallem, E. A., Ho, M. G. & Carlson, J. R. The molecular basis of odor coding in the Drosophila antenna. Cell 117, 965–979 (2004)

    Article  CAS  Google Scholar 

  12. Hallem, E. A. & Carlson, J. R. Coding of odors by a receptor repertoire. Cell 125, 143–160 (2006)

    Article  CAS  Google Scholar 

  13. Gaunt, M. W. & Miles, M. A. An insect molecular clock dates the origin of the insects and accords with palaeontological and biogeographic landmarks. Mol. Biol. Evol. 19, 748–761 (2002)

    Article  CAS  Google Scholar 

  14. Lu, T. et al. Odor coding in the maxillary palp of the malaria vector mosquito Anopheles gambiae . Curr. Biol. 17, 1533–1544 (2007)

    Article  CAS  Google Scholar 

  15. Malnic, B., Hirono, J., Sato, T. & Buck, L. B. Combinatorial receptor codes for odors. Cell 96, 713–723 (1999)

    Article  CAS  Google Scholar 

  16. Saito, H., Chi, Q., Zhuang, H., Matsunami, H. & Mainland, J. D. Odor coding by a mammalian receptor repertoire. Sci. Signal. 2, ra9 (2009)

    Article  Google Scholar 

  17. Wilson, R. I. & Mainen, Z. F. Early events in olfactory processing. Annu. Rev. Neurosci. 29, 163–201 (2006)

    Article  CAS  Google Scholar 

  18. Meijerink, J. et al. Identification of olfactory stimulants for Anopheles gambiae from human sweat samples. J. Chem. Ecol. 26, 1367–1382 (2000)

    Article  CAS  Google Scholar 

  19. Verhulst, N. O. et al. Cultured skin microbiota attracts malaria mosquitoes. Malar. J. 8, 302 (2009)

    Article  Google Scholar 

  20. Sun, H. et al. Alcohol, volatile fatty acid, phenol, and methane emissions from dairy cows and fresh manure. J. Environ. Qual. 37, 615–622 (2008)

    Article  CAS  Google Scholar 

  21. Gutiérrez-García, A. G., Contreras, C. M., Mendoza-Lopez, M. R., Garcia-Barradas, O. & Cruz-Sanchez, J. S. Urine from stressed rats increases immobility in receptor rats forced to swim: role of 2-heptanone. Physiol. Behav. 91, 166–172 (2007)

    Article  Google Scholar 

  22. TNO. Volatile Compounds in Food: Qualitative and Quantitative Data 〈http://www.vcf-online.nl〉 (2004)

  23. Morton, I. D. & MacLeod, A. J. The Flavour Of Fruits (Elsevier Science, 1990)

    Google Scholar 

  24. Millar, J. G., Chaney, J. D. & Mulla, M. S. Identification of oviposition attractants for culex-quinquefasciatus from fermented bermuda grass infusions. J. Am. Mosq. Control Assoc. 8, 11–17 (1992)

    CAS  PubMed  Google Scholar 

  25. Syed, Z. & Leal, W. S. Acute olfactory response of Culex mosquitoes to a human- and bird-derived attractant. Proc. Natl Acad. Sci. USA 106, 18803–18808 (2009)

    Article  ADS  CAS  Google Scholar 

  26. Blackwell, A. & Johnson, S. N. Electrophysiological investigation of larval water and potential oviposition chemo-attractants for Anopheles gambiae s.s. Ann. Trop. Med. Parasitol. 94, 389–398 (2000)

    Article  CAS  Google Scholar 

  27. Lindh, J. M., Kannaste, A., Knols, B. G. J., Faye, I. & Borg-Karlson, A. K. Oviposition responses of Anopheles Gambiae s.s. (Diptera: Culicidae) and identification of volatiles from bacteria-containing solutions. J. Med. Entomol. 45, 1039–1049 (2008)

    Article  CAS  Google Scholar 

  28. Kostelc, J. G., Preti, G., Zelson, P. R., Stoller, N. H. & Tonzetich, J. Salivary volatiles as indicators of periodontitis. J. Periodontal Res. 15, 185–192 (1980)

    Article  CAS  Google Scholar 

  29. Moore, S. J. & Debboun, M. in Insect Repellents: Principles, Methods, and Uses (eds Debboun, M., Frances, S. P. & Strickman, D.) 3–30 (CRC, 2007)

    Google Scholar 

  30. Omolo, M. O., Okinyo, D., Ndiege, I. O., Lwande, W. & Hassanali, A. Repellency of essential oils of some Kenyan plants against Anopheles gambiae . Phytochemistry 65, 2797–2802 (2004)

    Article  CAS  Google Scholar 

  31. Tangerman, A., Meuwesearends, M. T. & Vantongeren, J. H. M. A new sensitive assay for measuring volatile sulfur-compounds in human breath by tenax trapping and gas-chromatography and its application in liver-cirrhosis. clin. Chim. Acta 130, 103–110 (1983)

    Article  CAS  Google Scholar 

  32. Allan, S. A., Bernier, U. R. & Kline, D. L. Evaluation of oviposition substrates and organic infusions on collection of Culex in Florida. J. Am. Mosq. Control Assoc. 21, 268–273 (2005)

    Article  Google Scholar 

  33. Haddad, R. et al. A metric for odorant comparison. Nature Methods 5, 425–429 (2008)

    Article  CAS  Google Scholar 

  34. Logan, J. G. et al. Identification of human-derived volatile chemicals that interfere with attraction of Aedes aegypti mosquitoes. J. Chem. Ecol. 34, 308–322 (2008)

    Article  CAS  Google Scholar 

  35. Curran, A. M., Ramirez, C. F., Schoon, A. A. & Furton, K. G. The frequency of occurrence and discriminatory power of compounds found in human scent across a population determined by SPME-GEMS. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 846, 86–97 (2007)

    Article  CAS  Google Scholar 

  36. Curran, A. M., Rabin, S. I., Prada, P. A. & Furton, K. G. Comparison of the volatile organic compounds present in human odor using SPME-GC/MS. J. Chem. Ecol. 31, 1607–1619 (2005)

    Article  CAS  Google Scholar 

  37. Cork, A. & Park, K. C. Identification of electrophysiologically-active compounds for the malaria mosquito, Anopheles gambiae, in human sweat extracts. Med. Vet. Entomol. 10, 269–276 (1996)

    Article  CAS  Google Scholar 

  38. Bernier, U. R., Kline, D. L., Schreck, C. E., Yost, R. A. & Barnard, D. R. Chemical analysis of human skin emanations: comparison of volatiles from humans that differ in attraction of Aedes aegypti (Diptera: Culicidae). J. Am. Mosq. Control Assoc. 18, 186–195 (2002)

    CAS  PubMed  Google Scholar 

  39. Bernier, U. R., Kline, D. L., Barnard, D. R., Schreck, C. E. & Yost, R. A. Analysis of human skin emanations by gas chromatography/mass spectrometry. 2. Identification of volatile compounds that are candidate attractants for the yellow fever mosquito (Aedes aegypti). Anal. Chem. 72, 747–756 (2000)

    Article  CAS  Google Scholar 

  40. Gallagher, M. et al. Analyses of volatile organic compounds from human skin. Br. J. Dermatol. 159, 780–791 (2008)

    Article  CAS  Google Scholar 

  41. Kreher, S. A., Kwon, J. Y. & Carlson, J. R. The molecular basis of odor coding in the Drosophila larva. Neuron 46, 445–456 (2005)

    Article  CAS  Google Scholar 

  42. Benton, R., Vannice, K. S., Gomez-Diaz, C. & Vosshall, L. B. Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila . Cell 136, 149–162 (2009)

    Article  CAS  Google Scholar 

  43. Olsen, S. R. & Wilson, R. I. Lateral presynaptic inhibition mediates gain control in an olfactory circuit. Nature 452, 956–960 (2008)

    Article  ADS  CAS  Google Scholar 

  44. Schlief, M. L. & Wilson, R. I. Olfactory processing and behavior downstream from highly selective receptor neurons. Nature Neurosci. 10, 623–630 (2007)

    Article  CAS  Google Scholar 

  45. Yao, C. A., Ignell, R. & Carlson, J. R. Chemosensory coding by neurons in the coeloconic sensilla of the Drosophila antenna. J. Neurosci. 25, 8359–8367 (2005)

    Article  CAS  Google Scholar 

  46. Larsson, M. C. et al. Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction. Neuron 43, 703–714 (2004)

    Article  CAS  Google Scholar 

  47. Xia, Y. et al. The molecular and cellular basis of olfactory-driven behavior in Anopheles gambiae larvae. Proc. Natl Acad. Sci. USA 105, 6433–6438 (2008)

    Article  ADS  CAS  Google Scholar 

Download references

Acknowledgements

We thank W. van der Goes van Naters and C. Yao for help with electrophysiology, E. Hallem, S. Kreher, J. Salzman and T. Emonet for assistance with data analyses, and T.-W. Koh for comments on the manuscript. We thank P. Graham, Z. Berman, A. Rabin, M. Dillon and E. Kelley-Swift for technical assistance. We thank Y.-T. Qiu for assistance in generating Fig. 1b and Supplementary Fig. 1. This work was funded in part by grants from the Foundation for the National Institutes of Health (NIH) through the Grand Challenges in Global Health Initiative to L.J.Z., and from the NIH to L.J.Z. and J.R.C. A.F.C. is supported by an NIH Medical Scientist Training Program grant (2T32GM07205).

Author Contributions Electrophysiology and computational analysis were performed by A.F.C. Molecular cloning was performed by A.F.C., G.W. and C.-Y.S. A.F.C. and J.R.C. wrote the manuscript. All authors contributed to the design and interpretation of the study.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to John R. Carlson.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-8 with Legends, Supplementary Tables 1 & 3 Supplementary References and a Legend and References for Supplementary Table 2. (PDF 829 kb)

Supplementary Table

This file contains Supplementary Table 2 - see Supplementary Information file for Legend. (XLS 383 kb)

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carey, A., Wang, G., Su, CY. et al. Odorant reception in the malaria mosquito Anopheles gambiae. Nature 464, 66–71 (2010). https://doi.org/10.1038/nature08834

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature08834

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing