title: Identification of candidate mimicry proteins involved in parasite-driven phenotypic changes.
abstract: BACKGROUND
  Endoparasites with complex life cycles are faced with several biological challenges, as they need to occupy various ecological niches throughout their development. Host phenotypes that increase the parasite's transmission rate to the next host have been extensively described, but few mechanistic explanations have been proposed to describe their proximate causes. In this study we explore the possibility that host phenotypic changes are triggered by the production of mimicry proteins from the parasite by using an ecological model system consisting of the infection of the threespine stickleback (Gasterosteus aculeatus) by the cestode Schistocephalus solidus.
  
  
  METHODS
  Using RNA-seq data, we assembled 9,093 protein-coding genes from which ORFs were predicted to generate a reference proteome. Based on a previously published method, we built two complementary analysis pipelines to i) establish a general classification of protein similarity among various species (pipeline A) and ii) identify candidate mimicry proteins showing specific host-parasite similarities (pipeline B), a key feature underlying the possibility of molecular mimicry.
  
  
  RESULTS
  Ninety-four tapeworm proteins showed high local sequence homology with stickleback proteins. Four of these candidates correspond to secreted or membrane proteins that could be produced by the parasite and eventually be released in or be in contact with the host to modulate physiological pathways involved in various phenotypes (e.g. behaviors). One of these candidates belongs to the Wnt family, a large group of signaling molecules involved in cell-to-cell interactions and various developmental pathways. The three other candidates are involved in ion transport and post-translational protein modifications. We further confirmed that these four candidates are expressed in three different developmental stages of the cestode by RT-PCR, including the stages found in the host.
  
  
  CONCLUSIONS
  In this study, we identified mimicry candidate peptides from a behavior-altering cestode showing specific sequence similarity with host proteins. Despite their potential role in modulating host pathways that could lead to parasite-induced phenotypic changes and despite our confirmation that they are expressed in the developmental stage corresponding to the altered host behavior, further investigations will be needed to confirm their mechanistic role in the molecular cross-talk taking place between S. solidus and the threespine stickleback.
authors.affiliation: Institut de Biologie Intégrative et des Systèmes (IBIS), Département de Biologie, Université Laval, Pavillon Charles-Eugènes-Marchand, Québec, G1V 0A6, Canada. francois-olivier.gagnon-hebert.1@ulaval.ca.
authors.forename: Francois Olivier
authors.initials: FO
authors.lastname: Hebert
authors.affiliation: Department of Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, August-Thienemann-Str 2, 24306, Ploen, Germany. phelps@evolbio.mpg.de.
authors.forename: Luke
authors.initials: L
authors.lastname: Phelps
authors.affiliation: Department of Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, August-Thienemann-Str 2, 24306, Ploen, Germany. samonte@evolbio.mpg.de.
authors.forename: Irene
authors.initials: I
authors.lastname: Samonte
authors.affiliation: Department of Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, August-Thienemann-Str 2, 24306, Ploen, Germany. panchal@evolbio.mpg.de.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Panchal
authors.affiliation: Department of Biology, Adrian Building, Leicester University, University Road, Leicester, LE1 7RH, UK. sg369@leicester.ac.uk.
authors.forename: Stephan
authors.initials: S
authors.lastname: Grambauer
authors.affiliation: Department of Biology, Adrian Building, Leicester University, University Road, Leicester, LE1 7RH, UK. ib50@leicester.ac.uk.
authors.forename: Iain
authors.initials: I
authors.lastname: Barber
authors.affiliation: Department of Evolutionary Ecology, Max Planck Institute for Evolutionary Biology, August-Thienemann-Str 2, 24306, Ploen, Germany. kalbe@evolbio.mpg.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Kalbe
authors.affiliation: Institut de Biologie Intégrative et des Systèmes (IBIS), Département de Biologie, Université Laval, Pavillon Charles-Eugènes-Marchand, Québec, G1V 0A6, Canada. Christian.Landry@bio.ulaval.ca.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Landry
authors.affiliation: Institut de Biologie Intégrative et des Systèmes (IBIS), Département de Biologie, Université Laval, Pavillon Charles-Eugènes-Marchand, Québec, G1V 0A6, Canada. Nadia.Aubin-Horth@bio.ulaval.ca.
authors.forename: Nadia
authors.initials: N
authors.lastname: Aubin-Horth
mesh_terms: D000818:Animals; D002589:Cestoda / Q000254:growth & development*; D020869:Gene Expression Profiling; D015801:Helminth Proteins / Q000235:genetics / Q000378:metabolism*; D006790:Host-Parasite Interactions; D018716:Molecular Mimicry; D017386:Sequence Homology, Amino Acid; D023701:Smegmamorpha / Q000469:parasitology*
chemical_list: D015801:Helminth Proteins