title: Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows an extensive allelic divergence.
abstract: The protozoan parasite Trypanosoma cruzi, agent of Chagas' disease, displays an extensive genetic heterogeneity among strains and isolates. It is, therefore, important to determine the degree of polymorphism in potential candidates for drug design. Our studies on the organisation of the locus containing the gene encoding trypanothione synthetase (TcTRS) (an enzyme involved in the unique trypanothione pathway and hence a promising drug target) revealed a high degree of sequence polymorphism between the two alleles in the T. cruzi CL Brener strain, the reference clone for the genome project. The genes linked to the synthetase appeared to be involved in diverse cell-functions, not part of the trypanothione metabolism. The gene synteny was conserved at both allelic loci that were found to reside on a pair of homologous chromosomes with a size difference of about 2 Mb. The allelic polymorphism of TcTRS resulted in a protein sequence divergence of 4%, ten-times higher than in trypanothione reductase (TR), another key enzyme in the same pathway. Such allelic divergence observed in T. cruzi genes might have implications for drug design against Chagas' disease and the evolutional impact of the CL Brener strain.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Anh Nhi
authors.initials: AN
authors.lastname: Tran
authors.forename: Björn
authors.initials: B
authors.lastname: Andersson
authors.forename: Ulf
authors.initials: U
authors.lastname: Pettersson
authors.forename: Lena
authors.initials: L
authors.lastname: Aslund
mesh_terms: D000483:Alleles; D019732:Amide Synthases / Q000737:chemistry / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D014355:Chagas Disease / Q000469:parasitology; D002874:Chromosome Mapping; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000502:physiology; D012150:Polymorphism, Restriction Fragment Length; D016415:Sequence Alignment; D026801:Synteny / Q000235:genetics; D014349:Trypanosoma cruzi / Q000201:enzymology* / Q000235:genetics*
chemical_list: D016054:DNA, Protozoan; D019732:Amide Synthases; C064407:trypanothione synthetase