Single-nucleotide polymorphisms of the Trypanosoma cruzi MSH2 gene support the existence of three phylogenetic lineages presenting differences in mismatch-repair efficiency.
We have identified single-nucleotide polymorphisms (SNPs) in the mismatch-repair gene TcMSH2 from Trypanosoma cruzi. Phylogenetic inferences based on the SNPs, confirmed by RFLP analysis of 32 strains, showed three distinct haplogroups, denominated A, B, and C. Haplogroups A and C presented strong identity with the previously described T. cruzi lineages I and II, respectively. A third haplogroup (B) was composed of strains presenting hybrid characteristics. All strains from a haplogroup encoded the same specific protein isoform, called, respectively, TcMHS2a, TcMHS2b, and TcMHS2c. The classification into haplogroups A, B, and C correlated with variation in the efficiency of mismatch repair in these cells. When microsatellite loci of strains representative of each haplogroup were analyzed after being cultured in the presence of hydrogen peroxide, new microsatellite alleles were definitely seen in haplogroups B and C, while no evidence of microsatellite instability was found in haplogroup A. Also, cells from haplogroups B and C were considerably more resistant to cisplatin treatment, a characteristic known to be conferred by deficiency of mismatch repair in eukaryotic cells. Altogether, our data suggest that strains belonging to haplogroups B and C may have decreased mismatch-repair ability when compared with strains assigned to the haplogroup A lineage.
Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Caixa Postal 486, Belo Horizonte, Brazil.
Luiz
L
Augusto-Pinto
Santuza M R
SM
Teixeira
Sérgio D J
SD
Pena
Carlos Renato
CR
Machado
D019943:Amino Acid Substitution; D000818:Animals; D002945:Cisplatin / Q000378:metabolism; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics / Q000502:physiology; D042822:Genomic Instability; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D015800:Protozoan Proteins; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D015800:Protozoan Proteins; C435509:MSH2 protein, Trypanosoma cruzi; D051718:MutS Homolog 2 Protein; D002945:Cisplatin