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Adaptive divergence between incipient species of Anopheles gambiae increases resistance to Plasmodium.

ABSTRACT: The African malaria mosquito Anopheles gambiae is diversifying into ecotypes known as M and S forms. This process is thought to be promoted by adaptation to different larval habitats, but its genetic underpinnings remain elusive. To identify candidate targets of divergent natural selection in M and S, we performed genomewide scanning in paired population samples from Mali, followed by resequencing and genotyping from five locations in West, Central, and East Africa. Genome scans revealed a significant peak of M-S divergence on chromosome 3L, overlapping five known or suspected immune response genes. Resequencing implicated a selective target at or near the TEP1 gene, whose complement C3-like product has antiparasitic and antibacterial activity. Sequencing and allele-specific genotyping showed that an allelic variant of TEP1 has been swept to fixation in M samples from Mali and Burkina Faso and is spreading into neighboring Ghana, but is absent from M sampled in Cameroon, and from all sampled S populations. Sequence comparison demonstrates that this allele is related to, but distinct from, TEP1 alleles of known resistance phenotype. Experimental parasite infections of advanced mosquito intercrosses demonstrated a strong association between this TEP1 variant and resistance to both rodent malaria and the native human malaria parasite Plasmodium falciparum. Although malaria parasites may not be direct agents of pathogen-mediated selection at TEP1 in nature--where larvae may be the more vulnerable life stage--the process of adaptive divergence between M and S has potential consequences for malaria transmission.

SUBMITTER: White BJ

PROVIDER: S-EPMC3017163 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Adaptive divergence between incipient species of Anopheles gambiae increases resistance to Plasmodium.

White Bradley J BJ Lawniczak Mara K N MK Cheng Changde C Coulibaly Mamadou B MB Wilson Michael D MD Sagnon N'Fale N Costantini Carlo C Simard Frederic F Christophides George K GK Besansky Nora J NJ

Proceedings of the National Academy of Sciences of the United States of America 20101220 1

The African malaria mosquito Anopheles gambiae is diversifying into ecotypes known as M and S forms. This process is thought to be promoted by adaptation to different larval habitats, but its genetic underpinnings remain elusive. To identify candidate targets of divergent natural selection in M and S, we performed genomewide scanning in paired population samples from Mali, followed by resequencing and genotyping from five locations in West, Central, and East Africa. Genome scans revealed a signi ...[more]

PMID: 21173248

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Project description:Published data revealed that two of the 243 structural cuticular proteins of Anopheles gambiae, CPLCG3 and CPLCG4, are implicated in insecticide resistance and a third, CPF3, has far higher transcript levels in M than in S incipient species. We studied the distribution of transcripts for these three genes in the tissues of An. gambiae and the location of the proteins in the cuticle itself to gain information about how these cuticular proteins contribute to their important roles. Our data are consistent with CPLCG3/4 contributing to a thicker cuticle thus slowing penetration of insecticides and CPF3 possibly having a role in the greater desiccation tolerance of the M form.Using RT-qPCR, we established the temporal expression of the genes and by in situ hybridization we revealed the main tissues where their mRNAs are found. Electron microscopy immunolocalization, using secondary antibodies labeled with colloidal gold, allowed us to localize these proteins within different regions of the cuticle.The temporal expression of these genes overlaps, albeit with higher levels of transcripts from CPF3 in pharate adults and both CPLCG3 and CPLCG4 are higher in animals immediately after adult eclosion. The main location of mRNAs for all three genes is in appendages and genitalia. In contrast, the location of their proteins within the cuticle is completely different. CPF3 is found exclusively in exocuticle and CPLCG3/4 is restricted to the endocuticle. The other CPF gene expressed at the same times, CPF4, in addition to appendages, has message in pharate adult sclerites.The temporal and spatial differences in transcript abundance and protein localization help to account for An. gambiae devoting about 2% of its protein coding genes to structural cuticular proteins. The location of CPLCG3/4 in the endocuticle may contribute to the thickness of the cuticle, one of the recently appreciated components of insecticide resistance, while the location of CPF3 might be related to the greater desiccation resistance of the M form.

Project description:Transmission of malaria is dependent on the successful completion of the Plasmodium lifecycle in the Anopheles vector. Major obstacles are encountered in the midgut tissue, where most parasites are killed by the mosquito's immune system. In the present study, DNA microarray analyses have been used to compare Anopheles gambiae responses to invasion of the midgut epithelium by the ookinete stage of the human pathogen Plasmodium falciparum and the rodent experimental model pathogen P. berghei. Invasion by P. berghei had a more profound impact on the mosquito transcriptome, including a variety of functional gene classes, while P. falciparum elicited a broader immune response at the gene transcript level. Ingestion of human malaria-infected blood lacking invasive ookinetes also induced a variety of immune genes, including several anti-Plasmodium factors. Twelve selected genes were assessed for effect on infection with both parasite species and bacteria using RNAi gene silencing assays, and seven of these genes were found to influence mosquito resistance to both parasite species. An MD2-like receptor, AgMDL1, and an immunolectin, FBN39, showed specificity in regulating only resistance to P. falciparum, while the antimicrobial peptide gambicin and a novel putative short secreted peptide, IRSP5, were more specific for defense against the rodent parasite P. berghei. While all the genes that affected Plasmodium development also influenced mosquito resistance to bacterial infection, four of the antimicrobial genes had no effect on Plasmodium development. Our study shows that the impact of P. falciparum and P. berghei infection on A. gambiae biology at the gene transcript level is quite diverse, and the defense against the two Plasmodium species is mediated by antimicrobial factors with both universal and Plasmodium-species specific activities. Furthermore, our data indicate that the mosquito is capable of sensing infected blood constituents in the absence of invading ookinetes, thereby inducing anti-Plasmodium immune responses.

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Adaptive divergence between incipient species of Anopheles gambiae increases resistance to Plasmodium.

Publications

Adaptive divergence between incipient species of Anopheles gambiae increases resistance to Plasmodium.

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