The adaptive evolution divergence of triosephosphate isomerases between parasitic and free-living flatworms and the discovery of a potential universal target against flatworm parasites.

Triosephosphate isomerase (TIM) is an important drug target or vaccine candidate for pathogenetic organisms such as schistosomes. Parasitic and free-living flatworms shared their last common ancestor but diverged from each other for adapting to parasitic and free-living lives afterwards, respectively. Therefore, adaptive evolution divergence must have occurred between them. Here, for the first time, TIMs were identified from three free-living planarian flatworms, namely Dugesia japonica, Dugesia ryukyuensis, and Schmidtea mediterranea. When these were compared with parasitic flatworms and other organisms, the following results were obtained: (1) planarian TIM genes each contain only one intron, while parasitic flatworm genes each contain other four introns, which are usually present in common metazoans, suggesting planarian-specific intron loss must have occurred; (2) planarian TIM protein sequences are more similar to those of vertebrates rather than to their parasitic relatives or other invertebrates. This implies that relatively rapid evolution occurred in parasitic flatworm TIMs; (3) All the investigated parasitic flatworm TIMs contain a unique tripeptide insert (SXD/E), which may imply its insertion importance to the adaptation of parasitic life. Moreover, our homology modeling results showed the insert region was largely surface-exposed and predicted to be of a B cell epitope location. Finally, the insert is located within one of the three regions previously suggested to be promising immunogenic epitopes in Schistosoma mansoni TIM. Therefore, this unique insert might be significant to developing new effective vaccines or specific drugs against all parasitic flatworm diseases such as schistosomiasis and taeniosis/cysticercosis.