R. Jason Pitts, left, and A. Nicole Fox were co-authors of the paper with Zwiebel. (photos by Neil Brake)
Deciphering the genetic basis of the mosquitos’ senses
The researchers are trying to discover how insects like mosquitos can detect such a large range of different chemical signals with such a limited number of receptor types.
The mosquito Anopheles gambiae is something of a gourmet. It feeds almost exclusively on human blood. Its preference for humans and its ability to seek them out, in fact, are what makes the tiny insect such a deadly “vector” for the spread of malaria, a disease that causes millions of deaths annually.
Now researchers from Vanderbilt University, the University of Notre Dame and the University of Illinois at Urbana-Champaign have identified the genes that code for a special class of proteins that plays a critical role in almost every aspect of the insect’s life cycle, including its ability to see, taste, touch and smell.
“This is an important step forward in our ability to first understand the mosquitos’ host preference and tracking system and then to interfere with it in a way that can save human lives in an economically feasible and environmentally benign fashion,” said Laurence J. Zwiebel, Ph.D., assistant professor of Biological Sciences at Vanderbilt who led the study.
Writing in the Oct. 4 issue of the journal Science, Zwiebel and his colleagues report the identification of a total of 276 genes in the Anopheles gambiae genome that provide the blueprints for proteins called G-protein-coupled receptors (GFCRs) that are instrumental elements in the mosquito’s sensory systems, including those that it uses to find human prey.
The paper is part of a special issue of Science that reports the sequencing of the entire Anopheles genome. Concurrently, the journal Nature is announcing the sequencing of the genome of Plasmodium falciparum, the single-cell parasite carried by Anopheles that causes malaria. These two achievements are providing the impetus for a major new scientific assault on malaria and other mosquito-borne diseases.
In particular, Zwiebel and his colleagues report finding 79 genes that appear to be involved in the mosquito’s sense of smell and 72 involved in its sense of taste. Previous studies have shown that both of these chemosensory senses play a major role in the mosquitos’ strong preference for human hosts.
The identity of many of the genes was deduced from their predicted structural characteristics as well as their similarity to genes found in the fruit fly, Drosophila melanogaster. “In addition, we found a large number of genes that are unique to the mosquito and so could very well be involved in mosquito-specific behaviors such as blood feeding, host preference and tracking,” said Zwiebel.
In addition to the strong preference for human blood meals that is characteristic of A. gambiae, there are many closely related mosquito species that seek out other animals, including dogs, cats, birds, sheep, horses and cows, with similar single-minded tenacity.
“If we can identify the receptors that mosquitos use to smell humans, we should be able to design novel repellants and attractants that can substantially reduce the incidence of malaria, West Nile encephalitis, dengue and yellow fevers and other mosquito-born diseases,” Zwiebel said.
This goal appears to be achievable because the mosquitos’ olfactory system is substantially simpler than that of mammals. Humans have about 800 types of olfactory receptors while mice have about 1,200 compared with only 79 for the mosquito. In fact, an outstanding question is how insects like mosquitos can detect such a large range of different chemical signals with such a limited number of receptor types.
“We have a theory about how they do this that we are anxious to test,” said Zwiebel.
Co-authors of the paper with Zwiebel are A. Nicole Fox and R. Jason Pitts from Vanderbilt; Crystal A. Hall, Perciliz L. Tan, Mathew A. Chrystal and Frank H. Collins from Notre Dame; Lauren B. Kent and High M. Robertson from Urbana-Champaign; and Anibal Cravchik from Celera Diagnostics.
The research was funded by the United Nations Development Program/World Bank/World Health Organization Special Program for Research and Training in Tropical Diseases, National Institutes of Health, Celera and the Anopheles gambiae Genome Consortium.