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Background  Mosquitoes of the  Anopheles gambiae  species complex are the primary vectors of human malaria in sub-Saharan Africa. Many host genes have been shown to affect  Plasmodium  development in the mosquito, and so are expected to engage in an evolutionary arms race with the pathogen. However, there is little conclusive evidence that any of these mosquito genes evolve rapidly, or show other signatures of adaptive evolution.    Methods  Three serine protease inhibitors have previously been identified as candidate immune system genes mediating mosquito-Plasmodium interaction, and serine protease inhibitors have been identified as hot-spots of adaptive evolution in other taxa. Population-genetic tests for selection, including a recent multi-gene extension of the McDonald-Kreitman test, were applied to 16 serine protease inhibitors and 16 other genes sampled from the  An. gambiae  species complex in both East and West Africa.    Results  Serine protease inhibitors were found to show a marginally significant trend towards higher levels of amino acid diversity than other genes, and display extensive genetic structuring associated with the 2La chromosomal inversion. However, although serpins are candidate targets for strong parasite-mediated selection, no evidence was found for rapid adaptive evolution in these genes.    Conclusion  It is well known that phylogenetic and population history in the  An. gambiae  complex can present special problems for the application of standard population-genetic tests for selection, and this may explain the failure of this study to detect selection acting on serine protease inhibitors. The pitfalls of uncritically applying these tests in this species complex are highlighted, and the future prospects for detecting selection acting on the  An. gambiae  genome are discussed.

Inferring selection in the Anopheles gambiae species complex: an example from immune-related serine protease inhibitors