Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows an extensive allelic divergence

• Published in: Acta tropica Vol. 87; no. 2; pp. 269 - 278
• Main Authors: Tran, Anh-Nhi, Andersson, Björn, Pettersson, Ulf, Åslund, Lena
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.2003; Elsevier
• Subjects: Alleles; Amide Synthases - chemistry; Amide Synthases - genetics; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Chagas Disease - parasitology; Chromosome Mapping; CL Brener; DNA, Protozoan - chemistry; DNA, Protozoan - genetics; Genetic Variation - physiology; Human protozoal diseases; Humans; Infectious diseases; Medical sciences; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Molecular Sequence Data; Parasitic diseases; Polymerase Chain Reaction; Polymorphism, Genetic - physiology; Polymorphism, Restriction Fragment Length; Protozoal diseases; Sequence Alignment; Sequence polymorphism; Synteny - genetics; TcTRS-1CL; TcTRS-2CL; Tropical medicine; Trypanosoma cruzi; Trypanosoma cruzi - enzymology; Trypanosoma cruzi - genetics; Trypanosomiasis; Trypanothione synthetase; Trypanothione synthetase; CL Brener; TcTRS-1CL; Sequence polymorphism; TcTRS-2CL; Trypanosoma cruzi; Kinetoplastida; Protozoa; Carbon-nitrogen ligases; Enzyme; Ligases; Trypanothione synthase; Molecular biology; Polymorphism
• DOI: 10.1016/S0001-706X(03)00067-6
• ISSN: 0001-706X; 1873-6254

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.