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Identification of genes controlling the innate immune response in mosquitoes infected with the malaria parasite, Plasmodium

Final Activity Report Summary - ANOP-MAL-EVOL (Identification of genes controlling the innate immune response in mosquitoes infected with the malaria parasite, Plasmodium)

If the insect innate immune system is to be used as a potential blocking step in transmission of malaria, then it will require targeting one or a few genes with highest relevance and ease of manipulation. The problem is to identify and manipulate those of most importance to malaria infection without the risk of decreasing the mosquito's ability to stave off infections by microbes in general. Molecular evolution methodologies and concepts can help identify such genes. Within the setting of a comparative molecular population genetic and phylogenetic framework, involving six species of the Anopheles gambiae complex, we investigated whether a set of 14 pre-selected immunity genes (Gambicin, NOS, Rel2, FBN9, AgMDL1, CLIPB14, CLIPB1, LRIM1, CEC-1, GNBP-B1, LRRD5, LRRD8, FBN51 and TEP1) might have evolved under selection pressure imposed by the malaria parasite.

During the project 'Identification of genes controlling the innate immune response in mosquitoes infected with the malaria parasite, Plasmodium' (ANOP-MAL-EVOL), the study documented varying levels of polymorphism within and divergence between the species, in all the studied genes. Introgression and the sharing of ancestral polymorphisms, two processes that have been documented in the past, were verified in this study in all the involved genes. These processes appear to affect each gene in different ways and to different degrees. However, only one gene (LRIM1) was found to be exhibiting strong indications of positive selection and it is predicted that the alleles of this gene might vary in their level of resistance against P. falciparum.

Considering the results presented here in concert with previous studies, genes that interact directly with the Plasmodium parasite, and play little or no role in defence against other microbes, are probably the most likely candidates for a specific adaptive response against P. falciparum. Furthermore, since it is hard to establish direct evidence linking the adaptation of any candidate gene to P. falciparum infection, a comparative framework allowing at least an indirect link should be provided. Such a framework could be achieved, if a similar approach like the one involved here, was applied to all other anopheline complexes that transmit P. falciparum malaria. However, the amplification of the respective genes in Anopheles species other the ones belonging to the An. gambiae complex was not succesfull. This is a strong indication that these genes are marginally conserved within the Anophelines. Hence, issues concerning their physiological role in the other Anopheline species as well as the factors shaping their evolution are raised.