Developmental genomics of the most dangerous animal.

The poem unfortunately overstated the prospects for a victory over malaria. One hundred ten years later, we contemplate a disaster: more than a million deaths annually from malaria, and something on the order of 400 million malaria cases each year. In Africa, more than 100 children die from malaria every hour. The discovery that mosquitoes transmit malaria (1897–1898) earned Ronald Ross the Nobel Prize in 1902, anointing this insect as far and away the most dangerous animal to humans. Mosquitoes also transmit numerous other infections, including yellow fever, dengue, encephalitis, Rift Valley fever, West Nile virus, elephantiasis, . . . a WHO’s who of tragedy. The discovery of the malaria parasite, Plasmodium, in human blood samples (1880) earned Charles Alphonse Laveran, a French military doctor, the Nobel Prize in 1906. Plasmodium is a single-celled protozoan with truly astounding capabilities. Within that single cell lies the information necessary to evade not one but two advanced immune systems, and to go through several dramatic metamorphoses (Fig. 1). The latest contribution to the molecular biology of mosquito-borne diseases is a genomics view of gene activity during the life cycle of the malaria vector Anopheles gambiae, reported by Koutsos et al. in a recent issue of PNAS (2). The goal is to understand why A. gambiae is a malaria vector and how to stop it. Two mosquito genomes have been completed, A. gambiae and Aedes aegypti (3, 4), together with the genome of the deadliest malaria organism, Plasmodium falciparum (5). More than 90% of the Anopheles genes have a clear relative in other species (6). How are these genes deployed? Insect transcription was first observed as chromosome ‘‘puffs,’’ stagespecific swellings of the chromosomes that are often indicators of transcription activity. A map of puffs induced by ecdysone, the first indication in any animal of steroid-induced gene activity, set the stage for global views of transcription later (7). A comprehensive view began with the first insect genome completed, that of Drosophila melanogaster (8), and continues with the mosquito genomes (3, 4) and the honey bee (9). Drosophila and Anopheles ancestors diverged 250 million years ago. The Drosophila genome allowed analyses of the flux of RNA species during developmental time (10, 11), which can now be compared with Anopheles. Insect genomes, and knowledge of their activation patterns, will be useful in several ways, such as understanding evolution over the past half-billion years. Insects have evolved sophisticated chemical processing systems for constructing materials as amazing as spider silk and as pliable and impervious as cuticle, and for digesting and altering a vast range of natural substances. Genomics will reveal the enzymes that produce these materials and offer