Article | Published:

Evolution of mosquito preference for humans linked to an odorant receptor

Nature volume 515, pages 222227 (13 November 2014) | Download Citation

Abstract

Female mosquitoes are major vectors of human disease and the most dangerous are those that preferentially bite humans. A ‘domestic’ form of the mosquito Aedes aegypti has evolved to specialize in biting humans and is the main worldwide vector of dengue, yellow fever, and chikungunya viruses. The domestic form coexists with an ancestral, ‘forest’ form that prefers to bite non-human animals and is found along the coast of Kenya. We collected the two forms, established laboratory colonies, and document striking divergence in preference for human versus non-human animal odour. We further show that the evolution of preference for human odour in domestic mosquitoes is tightly linked to increases in the expression and ligand-sensitivity of the odorant receptor AaegOr4, which we found recognizes a compound present at high levels in human odour. Our results provide a rare example of a gene contributing to behavioural evolution and provide insight into how disease-vectoring mosquitoes came to specialize on humans.

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Accessions

Primary accessions

Sequence Read Archive

Data deposits

Raw RNA-seq data are available for download at the NCBI Sequence Read Archive (accession number SRP035216). Coding sequences of AaegOr4 alleles are at GenBank (accession numbers KF801614, KF801615 and KF801617KF801621).

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Acknowledgements

We thank M. K. N. Lawniczak, K. J. Lee, M. N. Nitabach, and the Vosshall laboratory for discussion and comments on the manuscript; J. E. Brown and J. R. Powell for discussion and coordination of field collections; W. Takken for advice regarding many aspects of this work; J.-P. Mutebi, B. Miller, and A. Ponlawat for live specimens from Uganda and Thailand; D. Beck, K. Nygaard, K. Prakash, and L. Seeholzer for expert technical assistance. We also thank X. Chen for pre-publication access to a draft Ae. albopictus genome assembly, and J. Liesch for access to Orlando strain RNA-seq data. We received valuable advice on collecting and working with forest and domestic forms of Ae. aegypti from M. Trpis, J. L. Peterson, and P. Lounibos, and on the design and use of two-port olfactometers from U. Bernier and V. Sherman. 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. This work was supported in part by the following National Institutes of Health grants: K99 award from NIDCD to C.S.M. (DC012069), an NIAID Vectorbase DBP subcontract to L.B.V. (HHSN272200900039C), and a CTSA award from NCATS (5UL1TR000043). R.I. received support from the Swedish Research Council and SLU: Insect Chemical Ecology and Evolution (IC-E3). L.B.V. is an investigator of the Howard Hughes Medical Institute.

Author information

Author notes

    • Carolyn S. McBride
    • , Felix Baier
    • , Aman B. Omondi
    •  & Sarabeth A. Spitzer

    Present addresses: Princeton Neuroscience Institute and Department of Ecology and Evolutionary Biology, Princeton University, Princeton, New Jersey 08544, USA (C.S.M.); Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA (F.B.); Plant Protection Research Institute, Agricultural Research Council, Private Bag X134, Queenswood 0121, South Africa (A.B.O.); Harvard College, Harvard University, Cambridge, Massachusetts 02138, USA (S.A.S.).

Affiliations

  1. Laboratory of Neurogenetics and Behavior, The Rockefeller University, New York, New York 10065, USA

    • Carolyn S. McBride
    • , Felix Baier
    • , Sarabeth A. Spitzer
    •  & Leslie B. Vosshall
  2. Howard Hughes Medical Institute, 1230 York Avenue, New York, New York 10065, USA

    • Carolyn S. McBride
    •  & Leslie B. Vosshall
  3. Unit of Chemical Ecology, Department of Plant Protection Biology, Swedish University of Agricultural Sciences, Box 102, Sundsvägen 14, 230 53 Alnarp, Sweden

    • Aman B. Omondi
    •  & Rickard Ignell
  4. Center for Virus Research, Kenya Medical Research Institute, PO Box 54840 – 00200, Off Mbagathi Way, Nairobi, Kenya

    • Joel Lutomiah
    •  & Rosemary Sang

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Contributions

C.S.M. and L.B.V. conceived the study. C.S.M. participated in the execution and analysis of all aspects of the study. J.L. helped coordinate mosquito collection in Rabai, Kenya under the supervision of R.S. S.A.S. helped design and carry out the morphological assays presented in Fig. 1e–i. F.B. helped clone, analyse, and genotype mosquitoes for the Or4 alleles presented in Fig. 5a–d, and construct transgenic Drosophila lines for use in single sensillum recordings. A.B.O. and R.I. designed, conducted, and analysed the GC–SSR and GC–MS experiments presented in Fig. 4 and carried out pilot experiments comprising dose–response curves and spontaneous activity analysis of alleles A and E, similar to those presented in Fig. 5e–g. C.S.M. and L.B.V. designed all other experiments, interpreted the results, designed the figures, and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Leslie B. Vosshall.

Extended data

Supplementary information

Excel files

  1. 1.

    Supplementary Table 1

    This file contains accession numbers and gene names (where known) for differentially expressed genes described in Fig. 3c-g.

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https://doi.org/10.1038/nature13964

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