title: Trypanosoma cruzi: Genome characterization of phosphatidylinositol kinase gene family (PIK and PIK-related) and identification of a novel PIK gene.
abstract: Chagas disease is caused by the protozoan Trypanosoma cruzi which affects 10 million people worldwide. Very few kinases have been characterized in this parasite, including the phosphatidylinositol kinases (PIKs) that are at the heart of one of the major pathways of intracellular signal transduction. Recently, we have classified the PIK family in T. cruzi using five different models based on the presence of PIK conserved domains. In this study, we have mapped PIK genes to the chromosomes of two different T. cruzi lineages (G and CL Brener) and determined the cellular localization of two PIK members. The kinases have crucial roles in metabolism and are assumed to be conserved throughout evolution. For this reason, they should display a conserved localization within the same eukaryotic species. In spite of this, there is an extensive polymorphism regarding PIK localization at both genomic and cellular levels, among different T. cruzi isolates and between T. cruzi and Trypanosomabrucei, respectively. We showed in this study that the cellular localization of two PIK-related proteins (TOR1 and 2) in the T. cruzi lineage is distinct from that previously observed in T. brucei. In addition, we identified a new PIK gene with peculiar feature, that is, it codes for a FYVE domain at N-terminal position. FYVE-PIK genes are phylogenetically distant from the groups containing exclusively the FYVE or PIK domain. The FYVE-PIK architecture is only present in trypanosomatids and in virus such as Acanthamoeba mimivirus, suggesting a horizontal acquisition. Our Bayesian phylogenetic inference supports this hypothesis. The exact functions of this FYVE-PIK gene are unknown, but the presence of FYVE domain suggests a role in membranous compartments, such as endosome. Taken together, the data presented here strengthen the possibility that trypanosomatids are characterized by extensive genomic plasticity that may be considered in designing drugs and vaccines for prevention of Chagas disease.
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Oliveira
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Fabio Mitsuo
authors.initials: FM
authors.lastname: Lima
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Mario Costa
authors.initials: MC
authors.lastname: Cruz
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Renata Carmona
authors.initials: RC
authors.lastname: Ferreira
authors.affiliation: Unidad Universitaria de Apoyo Bioinformático, Instituto de Biotecnología de la UNAM, Mexico.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanchez-Flores
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Esteban Maurício
authors.initials: EM
authors.lastname: Cordero
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Danielle Rodrigues
authors.initials: DR
authors.lastname: Cortez
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Éden Ramalho
authors.initials: ÉR
authors.lastname: Ferreira
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Marcelo Ribeiro da Silva
authors.initials: MR
authors.lastname: Briones
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: Renato Arruda
authors.initials: RA
authors.lastname: Mortara
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
authors.forename: José Franco
authors.initials: JF
authors.lastname: da Silveira
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP, Brazil; Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos 6627, Pampulha, Caixa Postal 486, Belo Horizonte, Minas Gerais CEP 31270-910, Brazil. Electronic address: dianabahia@hotmail.com.
authors.forename: Diana
authors.initials: D
authors.lastname: Bahia
mesh_terms: D001499:Bayes Theorem; D014355:Chagas Disease / Q000453:epidemiology; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D018503:Genome, Protozoan; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D015800:Protozoan Proteins / Q000235:genetics* / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000145:classification* / Q000201:enzymology* / Q000235:genetics
chemical_list: D015800:Protozoan Proteins; D019869:Phosphatidylinositol 3-Kinases
keywords: FYVE domain; FYVE-PIK; PIK; Phosphatidylinositol kinases; Target of rapamycin; Trypanosoma cruzi