SCIENCE INDEX 2000 2001 2002 Biology

Key sensory proteins unveiled in mosquito genome

Jim Barlow, Life Sciences Editor
(217) 333-5802; b-james3@uiuc.edu

10/2/02

CHAMPAIGN, Ill. — While studying tiny pieces of a genomic DNA sequence from the African malaria mosquito Anopheles gambiae on Christmas Eve 1999, entomologist Hugh Robertson of the University of Illinois at Urbana-Champaign found several possible olfactory receptors similar to those others had found in Drosophila fruit flies.

His discovery led to a comprehensive collaborative effort, the results of which will appear Oct. 4 along with the newly completed Anopheles gambiae genome in the journal Science. The journal made the announcement today. At the same time, the journal Nature announced it is publishing the Plasmodium falciparum genome on Oct. 3. Plasmodium, a single-celled parasite that causes malaria, is carried by Anopheles mosquitoes.

The completion of the Anopheles genome provides a new approach to the study of mosquitoes, including how to reduce the spread of malaria by the Anopheles mosquito and of diseases such as West Nile encephalitis, dengue and yellow fever by other mosquitoes.

With researchers at Vanderbilt University, the University of Notre Dame and Celera Diagnostics, Robertson identified 276 G protein-coupled receptors from the Anopheles genome. More than half (155) are external chemosensory receptors – among which are those that allow female mosquitoes to detect humans and other mammals by taste or smell. They found 79 olfactory (smell) receptors and 76 gustatory (taste) receptors.

"Our discoveries will hopefully shed light into host specificity, specifically how the combination of the olfactory and gustatory receptors help mosquitoes find their mammal hosts," Robertson said. "We know that mosquitoes can detect a whole bunch of chemicals that we humans release whether we like it or not, such as carbon dioxide and lactic acid. We don’t have a choice; we release them and they take advantage of that."

"Our paper provides a beginning description of all chemoreceptors, which are all the major kinds that detect signals outside of cells," Robertson said. "This provides the groundwork for going forward in the functional characterization of all of them, that is, determining which receptors detect which host chemicals."

Soon after his 1999 discovery, Robertson contacted Laurence J. Zwiebel, a biologist at Vanderbilt, who studies mosquitoes and is the corresponding author of the Science paper. In 2001, they collaborated on a paper in the Proceedings of the National Academy of Sciences that announced the discovery of five of the G protein-coupled receptors. Zwiebel is focusing on the olfactory receptors, while research on the gustatory proteins continues at Illinois by Robertson and doctoral student Lauren B. Kent, also a co-author.

Robertson and Kent, using advanced bioinformatics tools, also conducted a comprehensive molecular evolution evaluation of these chemoreceptors in the Anopheles mosquito and Drosophila genomes. Their work resulted in a phylogenic tree that depicts which receptors are in both genomes and which ones are in just one genome. The researchers conclude that while many of the receptors found in both insects are roughly equivalent, they evolved largely separately. "In other words," Robertson said, "the genes have duplicated and specialized differently in Drosophila and mosquitoes. The receptor proteins specific to each insect may account for the ability of fruit flies to detect rotten fruit and for mosquitoes to detect vertebrate hosts such as humans."

In addition to Robertson, Kent and Zwiebel, the authors of the paper are Catherine A. Hill, Perciliz L. Tan, Mathew A. Chrystal and Frank H. Collins, all of Notre Dame; A. Nicole Fox and R. Jason Pitts of Vanderbilt; and Anibal Cravchik of Celera Diagnostics.

The United Nations Development Programme/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases, the National Institutes of Health, Genoscope (through the French government) and the Anopheles gambiae Genome Consortium funded the research.