Natural malaria infection in Anopheles gambiae is regulated by a single genomic control region.

Center for Microbial and Plant Genomics and Department of Microbiology, University of Minnesota, St. Paul, MN 55108, USA.
Science (Impact Factor: 31.48). 05/2006; 312(5773):577-9. DOI: 10.1126/science.1124153
Source: PubMed

ABSTRACT We surveyed an Anopheles gambiae population in a West African malaria transmission zone for naturally occurring genetic loci that control mosquito infection with the human malaria parasite, Plasmodium falciparum. The strongest Plasmodium resistance loci cluster in a small region of chromosome 2L and each locus explains at least 89% of parasite-free mosquitoes in independent pedigrees. Together, the clustered loci form a genomic Plasmodium-resistance island that explains most of the genetic variation for malaria parasite infection of mosquitoes in nature. Among the candidate genes in this chromosome region, RNA interference knockdown assays confirm a role in Plasmodium resistance for Anopheles Plasmodium-responsive leucine-rich repeat 1 (APL1), encoding a leucine-rich repeat protein that is similar to molecules involved in natural pathogen resistance mechanisms in plants and mammals.

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    ABSTRACT: Anopheles gambiae is a major mosquito vector of malaria in Africa. While increased use of insecticide-based vector control tools have decreased malaria transmission, elimination is likely to require novel genetic control strategies. It can be argued that the absence of an An. gambiae inbred line has slowed progress towards genetic vector control. In order to empower genetic studies and enable precise and reproducible experimentation, we set out to create an inbred line of this species. We found that amenability to inbreeding varied between populations of An. gambiae. After full-sib inbreeding for 10 generations, we genotyped 112 individuals - 56 saved prior to inbreeding and 56 collected after inbreeding - at a genome wide panel of SNPs. While inbreeding dramatically reduced diversity across much of the genome, we discovered numerous, discrete genomic blocks that maintained high heterozygosity. For one large genomic region, we were able to definitively show that high diversity is due to the persistent polymorphism of a chromosomal inversion. Inbred lines in other eukaryotes often exhibit a qualitatively similar retention of polymorphism when typed at a small number of markers. Our whole genome SNP data provides the first strong, empirical evidence supporting associative overdominance as the mechanism maintaining higher than expected diversity in inbred lines. While creation of An. gambiae lines devoid of nearly all polymorphism may not be feasible, our results provide critical insights into how more fully isogenic lines can be created.
    Genome Biology and Evolution 11/2014; · 4.53 Impact Factor
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    ABSTRACT: Susceptibility to Plasmodium infection in Anopheles gambiae has been proposed to result from naturally occurring polymorphisms that alter the strength of endogenous innate defenses. Despite the fact that some of these mutations are known to introduce non-synonymous substitutions in coding sequences, these mutations have largely been used to rationalize knockdown of associated target proteins to query the effects on parasite development in the mosquito host. Here, we assay the effects of engineered mutations on an immune signaling protein target that is known to control parasite sporogonic development. By this proof-of-principle work, we have established that naturally occurring mutations can be queried for their effects on mosquito protein function and on parasite development and that this important signaling pathway can be genetically manipulated to enhance mosquito resistance.
    Parasites & Vectors 06/2014; 7(1):287. · 3.25 Impact Factor
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    ABSTRACT: Chromosomal inversions have been repeatedly involved in local adaptation in a large number of animals and plants. The ecological and behavioral plasticity of Anopheles species-human malaria vectors-is mirrored by high amounts of polymorphic inversions. The adaptive significance of chromosomal inversions has been consistently attested by strong and significant correlations between their frequencies and a number of phenotypic traits. Here, we provide an extensive literature review of the different adaptive traits associated with chromosomal inversions in the genus Anopheles. Traits having important consequences for the success of present and future vector control measures, such as insecticide resistance and behavioral changes, are discussed.
    Frontiers in Genetics 01/2014; 5:129.

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