Malaria has been with us for thousands of years — Alexander the Great and Oliver Cromwell are thought to have been among its victims. Mosquito resistance to insecticides has thwarted efforts to control the disease. But the limited understanding of mosquito biology that made us lose this battle is set to change with the publication in Science of the genome sequence of Anopheles gambiae, the principle vector of the malaria parasite Plasmodium falciparum. This sequence and its accompanying analysis, together with the publication of the P. falciparum genome (see above Highlight) provide vitally important information in the fight to control malaria transmission.
The combined efforts of Celera, GenoScope and TIGR produced a tenfold shotgun coverage of the A. gambiae genome. At 278 Mb, it is more than twice the size of the fruitfly genome, mainly because of the expansion of non-coding DNA. The A. gambiae genome is also highly variable. Most of the variable regions in the sequenced strain fall into two haplotypes, suggesting that it derives from two genetically distinct populations. This variation might be of use in the future — for example, SNP markers should allow malaria researchers to follow the evolution and the spread of insecticide resistance genes.
The analysis of the genome revealed several key features of the A. gambiae genome. Gene-prediction algorithms indicate that A. gambiae has ∼15,000 genes. A comparison between mosquito and fly genomes and proteomes revealed that, despite considerable similarities, there were significant differences — a sign of adaptation to different life strategies and a target for altering the mosquito's life cycle and its vector properties.
Other reports in this issue of Science include an analysis of immunity-related genes, and of those that encode neuropeptides, peptide hormones and G-protein-coupled receptors. These gene products are involved in different aspects of the mosquito's biology and behaviour, such as its response to the malaria parasite, taste for the human host and its reproduction. Which of them should be targeted to break the malaria life cycle remains to be seen.
A wealth of information on genome structure, evolution and function, and on insect biology can be found in this collection of papers. The direct application of these, and future, findings to the control of malaria is the next pressing goal.
References
ORIGINAL RESEARCH PAPERS
Holt, R. A. et al. The genome sequence of the malaria mosquito Anopheles gambiae. Science 298, 129–149 (2002)
Zdobnov, E. M. et al. Comparative genome and proteome analysis of Anopheles gambiae and Drosophila melanogaster. Science 298, 149–159 (2002)
FURTHER READING
Christophides, G. K. et al. Immunity-related genes and gene families in Anopheles gambiae. Science 298, 159–165 (2002)
Riehle, M. A. et al. Neuropeptides and peptide hormones in Anopheles gambiae. Science 298, 172–175 (2002)
Hill, C. A. et al. G protein-coupled receptors in Anopheles gambiae. Science 298, 176–178 (2002)
Ranson, H. et al. Evolution of supergene families associated with insecticide resistance. Science 298, 179–181 (2002)
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Skipper, M. Deadly vector unveiled. Nat Rev Genet 3, 820 (2002). https://doi.org/10.1038/nrg941
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DOI: https://doi.org/10.1038/nrg941
