The evolution of TEP1, an exceptionally polymorphic immunity gene in Anopheles gambiae

Abstract

BackgroundHost-parasite coevolution can result in balancing selection, which maintains genetic variation in the susceptibility of hosts to parasites. It has been suggested that variation in a thioester-containing protein called TEP1 (AGAP010815) may alter the ability of Anopheles mosquitoes to transmit Plasmodium parasites, and high divergence between alleles of this gene suggests the possible action of long-term balancing selection. We studied whether TEP1 is a case of an ancient balanced polymorphism in an animal immune system.ResultsWe found evidence that the high divergence between TEP1 alleles is the product of genetic exchange between TEP1 and other TEP loci, i.e. gene conversion. Additionally, some TEP1 alleles showed unexpectedly low variability.ConclusionThe TEP1 gene appears to be a chimera produced from at least two other TEP loci, and the divergence between TEP1 alleles is probably not caused by long-term balancing selection, but is instead due to two independent gene conversion events from one of these other genes. Nevertheless, TEP1 still shows evidence of natural selection, in particular there appears to have been recent changes in the frequency of alleles that has diminished polymorphism within each allelic class. Although the selective force driving this dynamic was not identified, given that susceptibility to Plasmodium parasites is known to be associated with allelic variation in TEP1, these changes in allele frequencies could alter the vectoring capacity of populations.

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

“…The TEP1r A and TEP1r B subclusters differ by five fixed (or nearly fixed) amino acid replacements caused by six nonsynonymous nucleotide substitutions. Alleles within both subclusters have been previously recorded (22,27), but neither the partitioning of sequence variation between subclusters nor their differential distribution between molecular forms of An. gambiae was appreciated.…”

“…Corresponding TEP1 alleles (TEP1r and TEP1s) also segregate in natural populations of An. gambiae and its sibling species Anopheles arabiensis (26,27). The majority of substitutions between these highly divergent alleles are found in the thioester binding domain (TED) where our TEP1 sequence survey was focused.…”

“…The TEP1r B subcluster contains only M-form alleles, found only in M sampled from Mali, Burkina Faso, and Ghana. This TEP1r B subcluster also contains the allele segregating in the M-form Mali-NIH strain and alleles sampled (exclusively) from Burkina Faso by Obbard et al (27), but that study did not distinguish between M and S forms. Obbard et al (27) Fig.…”

“…The TEP1r A subcluster contains the phenotypically resistant allele from the 4Arr laboratory strain (named Tep1*R2; ref. 22), as well as all TEP1r alleles sampled by Obbard et al (27) from An. gambiae natural populations in Cameroon and Kenya.…”

“…The majority of substitutions between these highly divergent alleles are found in the thioester binding domain (TED) where our TEP1 sequence survey was focused. To compare the M-and S-form TEP1 sequences obtained in this study with previously reported TEP1r and TEP1s alleles from natural populations and laboratory colonies (22,26,27), we performed a multiple sequence alignment on the basis of amino acid sequences deduced from the TED region (abridged in Fig. 3, for clarity).…”