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Open Access Highly Accessed Research article

The molecular evolution of four anti-malarial immune genes in the Anopheles gambiae species complex

Aristeidis Parmakelis14*, Michel A Slotman1, Jonathon C Marshall15, Parfait H Awono-Ambene2, Christophe Antonio-Nkondjio2, Frederic Simard23, Adalgisa Caccone1 and Jeffrey R Powell1

Author Affiliations

1 Department of Ecology and Evolutionary Biology, Yale University, 21 Sachem Street, 06511, New Haven, CT, USA

2 Organisation de Coordination pour la Lutte Contre les Endémies en Afrique Centrale (OCEAC), P.O. Box 288, Yaoundé, Cameroon

3 Institute de Recherche pour le Développement (IRD), UR016, BP 1857, Yaoundé, Cameroon

4 Department of Biology, University of Crete, P.O. Box 2208, GR-71409, Heraklion, Crete, Greece

5 Department of Biology, Southern Utah University, Science Center 105, 84720, Cedar City, UT, USA

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BMC Evolutionary Biology 2008, 8:79  doi:10.1186/1471-2148-8-79

Published: 6 March 2008

Abstract

Background

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 four pre-selected immunity genes (gambicin, NOS, Rel2 and FBN9) might have evolved under selection pressure imposed by the malaria parasite.

Results

We document varying levels of polymorphism within and divergence between the species, in all four genes. Introgression and the sharing of ancestral polymorphisms, two processes that have been documented in the past, were verified in this study in all four studied genes. These processes appear to affect each gene in different ways and to different degrees. However, there is no evidence of positive selection acting on these genes.

Conclusion

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 defense 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.