title: De novo discovery of neuropeptides in the genomes of parasitic flatworms using a novel comparative approach.
abstract: Neuropeptide mediated signalling is an ancient mechanism found in almost all animals and has been proposed as a promising target for the development of novel drugs against helminths. However, identification of neuropeptides from genomic data is challenging, and knowledge of the neuropeptide complement of parasitic flatworms is still fragmentary. In this work, we have developed an evolution-based strategy for the de novo discovery of neuropeptide precursors, based on the detection of localised sequence conservation between possible prohormone convertase cleavage sites. The method detected known neuropeptide precursors with good precision and specificity in the models Drosophila melanogaster and Caenorhabditis elegans. Furthermore, it identified novel putative neuropeptide precursors in nematodes, including the first description of allatotropin homologues in this phylum. Our search for neuropeptide precursors in the genomes of parasitic flatworms resulted in the description of 34 conserved neuropeptide precursor families, including 13 new ones, and of hundreds of new homologues of known neuropeptide precursor families. Most neuropeptide precursor families show a wide phylogenetic distribution among parasitic flatworms and show little similarity to neuropeptide precursors of other bilaterian animals. However, we could also find orthologs of some conserved bilaterian neuropeptides including pyrokinin, crustacean cardioactive peptide, myomodulin, neuropeptide-Y, neuropeptide KY and SIF-amide. Finally, we determined the expression patterns of seven putative neuropeptide precursor genes in the protoscolex of Echinococcus multilocularis. All genes were expressed in the nervous system with different patterns, indicating a hidden complexity of peptidergic signalling in cestodes.
authors.affiliation: Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Iguá 4225, CP11400 Montevideo, Uruguay. Electronic address: ukoziol@gmail.com.
authors.forename: Uriel
authors.initials: U
authors.lastname: Koziol
authors.affiliation: Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Iguá 4225, CP11400 Montevideo, Uruguay.
authors.forename: Miguel
authors.initials: M
authors.lastname: Koziol
authors.affiliation: Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Iguá 4225, CP11400 Montevideo, Uruguay.
authors.forename: Matías
authors.initials: M
authors.lastname: Preza
authors.affiliation: Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Iguá 4225, CP11400 Montevideo, Uruguay.
authors.forename: Alicia
authors.initials: A
authors.lastname: Costábile
authors.affiliation: University of Würzburg, Institute for Hygiene and Microbiology, Josef-Schneider-Straße 2 / Bau E1, 97080 Würzburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brehm
authors.affiliation: Sección Bioquímica, Facultad de Ciencias, Universidad de la República, Iguá 4225, CP11400 Montevideo, Uruguay.
authors.forename: Estela
authors.initials: E
authors.lastname: Castillo
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry; D029721:Drosophila Proteins / Q000737:chemistry; D004331:Drosophila melanogaster / Q000737:chemistry / Q000235:genetics*; D048210:Echinococcus multilocularis / Q000737:chemistry / Q000235:genetics; D049751:Genome, Helminth; D015801:Helminth Proteins / Q000737:chemistry; D006801:Humans; D017403:In Situ Hybridization; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D010802:Phylogeny; D010932:Planarians / Q000737:chemistry / Q000235:genetics*; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification*; D012680:Sensitivity and Specificity; D016415:Sequence Alignment; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D015801:Helminth Proteins; D009479:Neuropeptides; D011498:Protein Precursors
keywords: Cestode; In silico; Neuropeptide; Peptide hormone; Planarian; Trematode