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.ecological speciation | malaria vector | population genomics | thioester immune gene

Some strains of Plasmodium falciparum , a human malaria parasite, evade the complement-like system of Anopheles gambiae mosquitoes

“…The TEP1-R1 allele seems to be the result of recombination of the r A and r B TEP1 alleles that are present at high frequency in some African populations of A. gambiae (18). The r B allele is also dominant for P. berghei melanotic encapsulation, but heterozygous S/r B females do not melanize P. falciparum (ND37 strain) parasites (18).…”

“…The TEP1-R1 allele present in R mosquitoes has been shown to be a major determinant of P. berghei melanotic encapsulation (13), and it is closely related to the r B allele that is fixed in some M-form A. gambiae populations from Mali and Burkina Faso (18). The TEP1-R1 allele seems to be the result of recombination of the r A and r B TEP1 alleles that are present at high frequency in some African populations of A. gambiae (18).…”

“…The TEP1-R1 allele seems to be the result of recombination of the r A and r B TEP1 alleles that are present at high frequency in some African populations of A. gambiae (18). The r B allele is also dominant for P. berghei melanotic encapsulation, but heterozygous S/r B females do not melanize P. falciparum (ND37 strain) parasites (18). This difference in the ability to melanize P. berghei and P. falciparum is similar to what we observed in the L3-5/G3 colony cross, indicating that the R1 or r B TEP1 alleles are enough to melanize P. berghei but not P. falciparum.…”

“…In contrast, LRIM1 silencing in the A. gambiae Younde strain from Cameroon had no effect on sympatric P. falciparum isolates (17). More recent studies have shown that the TEP1-r B allele found in natural populations of A. gambiae mosquitoes is associated with higher P. falciparum (ND37 strain, a line derived from NF54) infection than the TEP1-S allele (18). In general, the TEP1 system seems to be more effective in eliminating P. berghei than P. falciparum.…”

Pollutants and insecticides drive local adaptation in African malaria mosquitoes

“…gambiae s.l. In that respect, patterns of genomic divergence have started to be dissected and significant insights have been gained into the signatures of selection among continental populations Neafsey et al 2010;White et al 2011). However, ecological divergence and local adaptation within species of the An.…”