This project aims at the identification of the genes controlling the innate immune response in mosquitoes infected with the malaria parasite, Plasmodium. There is ample evidence that mosquitoes and the malaria parasite have co-evolved and that the immune system of the mosquito greatly affects the ability of the parasite to undergo rather complex development in the insect. A large number of genes are involved in insect immunity, most of which have been identified in Anopheles gambiae. In order to debilitate the insect's immune response system (and thus lower its fitness), ideally one would want to identify genes specific to a particular mosquito species and particular parasite species. The fact that the deadliest form of human malaria, that caused by P. falciparum, is transmitted by only five species of Anopheles in continental Africa and these represent four independent evolutionarily events, is of outmost importance for the current project. The four natural replicates will be used to determine the common pat terns specifically associated with the specific species of malaria parasite. In particular, the patterns of amino acid substitutions in genes involved in the insect's immune system will be analyzed. Adequate evidence exists in support of the view that prot eins involved in host-parasite interactions undergo rapid evolution when the association arises. This association has arisen four independent times, thus making the evolutionary approach to identify crucial proteins particularly promising. Hundreds or thou sands of years of evolution will be exploited in order to reveal specific interactions that have arisen under natural conditions.
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