Author:
White Bradley J.,Lawniczak Mara K. N.,Cheng Changde,Coulibaly Mamadou B.,Wilson Michael D.,Sagnon N'Fale,Costantini Carlo,Simard Frederic,Christophides George K.,Besansky Nora J.
Abstract
The African malaria mosquitoAnopheles gambiaeis 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 theTEP1gene, whose complement C3-like product has antiparasitic and antibacterial activity. Sequencing and allele-specific genotyping showed that an allelic variant ofTEP1has 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,TEP1alleles of known resistance phenotype. Experimental parasite infections of advanced mosquito intercrosses demonstrated a strong association between thisTEP1variant and resistance to both rodent malaria and the native human malaria parasitePlasmodium falciparum. Although malaria parasites may not be direct agents of pathogen-mediated selection atTEP1in 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.
Publisher
Proceedings of the National Academy of Sciences
Cited by
92 articles.
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