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

BACKGROUND: Host-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. RESULTS: We 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. CONCLUSION: The 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.

Four abundant novel transcript genes from Toxocara canis with unrelated coding sequences share untranslated region tracts implicated in the control of gene expression.

The Toxocara canis "abundant novel transcripts" (ant) are four highly expressed products, constituting >18% of ESTs from the infective stage of this widely prevalent nematode parasite. Using 5' RACE, we determined full-length sequences for each ant gene, between 1.8 and 2.8kb. The four genes (termed ant-3, -5, -30 and -34), share no coding sequence similarity, although their 3'UTRs (untranslated regions) are homologous. Predicted ANT-5 and ANT-30 proteins show distant similarity to RNA regulatory proteins, RNA-dependent RNA polymerase and DEAH-box helicase, respectively. Surprisingly, ant-3 appears to be bi-cistronic, encoding two ORFs (ANT-3.1 and -3.2), each with a predicted N-terminal signal sequence. Antibodies raised to recombinant proteins did not react with native parasite products, indicating that protein expression did not accord with transcript abundance. However, antibody reactivity to two gene products (ANT-3.1 and ANT-34) was present in patient sera, suggesting that these proteins are synthesized later in infection. To test whether 3'UTRs may regulate expression, the ant-34 3'UTR sequence was inserted adjacent to enhanced green fluorescent protein (EGFP) for transformation of Caenorhabditis elegans. The ant-34 3'UTR greatly reduced EGFP expression, inhibiting both transcription and translation. We identified a tract in this UTR with significant sequence complementarity to the C. elegans micro-RNA lin-4. While infective stage parasites stockpile high levels of the ant transcripts, we suggest that translation is repressed, possibly by a mechanism involving 3' UTR motifs shared by the four genes.