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

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. (C) 2003 Elsevier Science B.V. All rights reserved.