title: Fast evolutionary rates associated with functional loss in class I glucose transporters of Schistosoma mansoni.
abstract: BACKGROUND
  The trematode parasite, Schistosoma mansoni, has evolved to switch from oxidative phosphorylation to glycolysis in the presence of glucose immediately after invading the human host. This metabolic switch is dependent on extracellular glucose concentration. Four glucose transporters are encoded in the genome of S. mansoni, however, only two were shown to facilitate glucose diffusion.
  
  
  RESULTS
  By modeling the phase of human host infection, we showed that transporter transcript expression profiles of recently transformed schistosomula have two opposing responses to increased glucose concentrations. Concurring with the transcription profiles, our phylogenetic analyses revealed that S. mansoni glucose transporters belong to two separate clusters, one associated with class I glucose transporters from vertebrates and insects, and the other specific to parasitic Platyhelminthes. To study the evolutionary paths of both groups and their functional implications, we determined evolutionary rates, relative divergence times, genomic organization and performed structural analyses with the protein sequences. We finally used the modelled structures of the S. mansoni glucose transporters to biophysically (i) analyze the dynamics of key residues during glucose binding, (ii) test glucose stability within the active site, and (iii) demonstrate glucose diffusion. The two S. mansoni Platyhelminthes-specific glucose transporters, which seem to be younger than the other two, exhibit slower rates of molecular evolution, are encoded by intron-poor genes, and transport glucose. Interestingly, our molecular dynamic analyses suggest that S. mansoni class I glucose transporters are not able to transport glucose.
  
  
  CONCLUSIONS
  The glucose transporter family in S. mansoni exhibit different evolutionary histories. Our results suggested that S. mansoni class I glucose transporters lost their capacity to transport glucose and that this function evolved independently in the Platyhelminthes-specific glucose transporters. Finally, taking into account the differences in the dynamics of glucose transport of the Platyhelminthes-specific transporters of S. mansoni compared to that of humans, we conclude that S. mansoni glucose transporters may be targets for rationally designed drugs against schistosomiasis.
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000, Lille, France. cabezasalejandrocruz@gmail.com.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Cabezas-Cruz
authors.affiliation: Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic, 37005, České Budějovice, Czech Republic. valdjj@gmail.com.
authors.forename: James J
authors.initials: JJ
authors.lastname: Valdés
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000, Lille, France. julien.lancelot@pasteur-lille.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Lancelot
authors.affiliation: Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000, Lille, France. raymond.pierce@pasteur-lille.fr.
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pierce
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D019143:Evolution, Molecular; D005947:Glucose / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006790:Host-Parasite Interactions; D006801:Humans; D007438:Introns / Q000235:genetics; D007814:Larva / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D012550:Schistosoma mansoni / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic
chemical_list: D051246:Glucose Transport Proteins, Facilitative; D005947:Glucose