aetiologic agents of West Nile encephalitis, Eastern equine encephalitis, Venezuelan equine encephalitis, Japanese encephalitis, St. Louis encephalitis, Ross River encephalitis, Murray Valley encephalitis, Rift valley

1. Justification for a Culex pipiens quinquefasciatus Genome Project. Culex species are important vectors of human pathogens in the United States and world-wide, including the aetiologic agents of West Nile encephalitis, Eastern equine encephalitis, Venezuelan equine encephalitis, Japanese encephalitis, St. Louis encephalitis, Ross River encephalitis, Murray Valley encephalitis, Rift valley fever, and lymphatic filariases. The most important of the Culex vectors are members of the Culex pipiens complex, a very closely related group of species (or incipient species the taxonomy remains unclear) that originated in Africa but has spread by human activity to tropical and temperate climate zones on all continents but Antarctica. More than 100 million people are infected worldwide with the Wuchereria bancrofti form of lymphatic filariasis that is transmitted primarily by Cx. pipiens complex mosquitoes in urban and suburban settings, and approximately 43 million filariasis cases are seriously disabled (UNDP/World Bank/WHO/TDR and WHO/UNICEF “Research on Rapid Geographical Assessment of Bancroftian Filariasis” July, 1997). It has been estimated that 750 million people are exposed to filariasis every year (WHO Expert Committee on Filariasis, 1992). Recently, both Cx. pipiens pipiens (Northern house mosquito) and Cx. pipiens quinquefasciatus (Southern house mosquito), together with Cx. tarsalis and several other Culex species, have attracted much attention within the United States and Canada as significant vectors of West Nile Virus. When one considers the number of human pathogenic viruses that Culex species transmit combined with the numbers of people afflicted, in some form, with lymphatic filariasis, the overall disease burden created by members of the genus Culex is very large. This burden caused by Culex species exceeds those of dengue and yellow fever transmitted by Aedes aegypti (estimated at ~ 20 million) and the number of people who are HIVpositive ( ~ 42 million). The combination of both the global distribution of the Cx. pipiens complex and its distribution within the United States as both a rural and urban mosquito species, also makes this mosquito a potential vector for mosquito-borne pathogens released for the purposes of bioterrorism. The genome sequence of a member of the Cx. pipiens complex would greatly simplify the identification of mosquito genes required for pathogen transmission, potentially enabling the development of new strategies for combating and controlling these diseases. Furthermore, initiation of a Cx. pipiens complex species genome project would complement ongoing work with Anopheles gambiae (draft genome completed) and Aedes aegypti (extensive EST and BAC end sequencing underway) and lead to the completion of draft genomes of the three most important mosquito vectors of human pathogens. Comprehensive comparisons between representatives of these three mosquito genera will also greatly inform the evolutionary relationships among these species and perhaps lead to advances in our understanding of mosquito genes involved in important phenomena like vectorial capacity and insecticide resistance. The genome of a Cx. pipiens complex species will also be invaluable in helping illuminate mechanism whereby the endosymbiotic organism Wolbachia (first discovered in Cx. pipiens) is responsible for phenomena like cytoplasmic incompatibility in mosquitoes and other insects.