title: 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.
authors.affiliation: Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: White
authors.forename: Mara K N
authors.initials: MK
authors.lastname: Lawniczak
authors.forename: Changde
authors.initials: C
authors.lastname: Cheng
authors.forename: Mamadou B
authors.initials: MB
authors.lastname: Coulibaly
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wilson
authors.forename: N'Fale
authors.initials: N
authors.lastname: Sagnon
authors.forename: Carlo
authors.initials: C
authors.lastname: Costantini
authors.forename: Frederic
authors.initials: F
authors.lastname: Simard
authors.forename: George K
authors.initials: GK
authors.lastname: Christophides
authors.forename: Nora J
authors.initials: NJ
authors.lastname: Besansky
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics* / Q000276:immunology; D000349:Africa; D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000235:genetics* / Q000276:immunology / Q000469:parasitology*; D001483:Base Sequence; D003433:Crosses, Genetic; D040461:Gene Components; D049810:Genetic Speciation; D005828:Genetics, Population; D005838:Genotype; D005843:Geography; D007113:Immunity, Innate / Q000235:genetics*; D019476:Insect Proteins / Q000235:genetics*; D046228:Microarray Analysis; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000276:immunology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D019476:Insect Proteins; C544265:TEP1 protein, Anopheles gambiae