Identification of three single nucleotide polymorphisms in Anopheles gambiae immune signaling genes that are associated with natural Plasmodium falciparum infection

BACKGROUND: Laboratory studies have demonstrated that a variety of immune signaling pathways regulate malaria parasite infection in Anopheles gambiae, the primary vector species in Africa. METHODS: To begin to understand the importance of these associations under natural conditions, an association mapping approach was adopted to determine whether single nucleotide polymorphisms (SNPs) in selected immune signaling genes in A. gambiae collected in Mali were associated with the phenotype of Plasmodium falciparum infection. RESULTS: Three SNPs were identified in field-collected mosquitoes that were associated with parasite infection in molecular form-dependent patterns: two were detected in the Toll5B gene and one was detected in the gene encoding insulin-like peptide 3 precursor. In addition, one infection-associated Toll5B SNP was in linkage disequilibrium with a SNP in sequence encoding a mitogen-activated protein kinase that has been associated with Toll signaling in mammalian cells. Both Toll5B SNPs showed divergence from Hardy-Weinberg equilibrium, suggesting that selection pressure(s) are acting on these loci. CONCLUSIONS: Seven of these eight infection-associated and linked SNPs alter codon frequency or introduce non-synonymous changes that would be predicted to alter protein structure and, hence, function, suggesting that these SNPs could alter immune signaling and responsiveness to parasite infection.