Single-Nucleotide Polymorphisms of the Trypanosoma cruzi MSH2 Gene Support the Existence of Three Phylogenetic Lineages Presenting Differences in Mismatch-Repair Efficiency

Single-Nucleotide Polymorphisms of the Trypanosoma cruzi MSH2 Gene Support the Existence of Three Phylogenetic Lineages Presenting Differences in Mismatch-Repair Efficiency

Luiz Augusto-Pinto^a, Santuza M. R. Teixeira^a, Sérgio D. J. Pena^a, and Carlos Renato Machado^a
^a Department of Biochemistry and Immunology, Universidade Federal de Minas Gerais, Caixa Postal 486, Belo Horizonte, Brazil

Corresponding author: Carlos Renato Machado, ICB, UFMG Av. Antônio Carlos, 6627, Caixa Postal 486, Belo Horizonte, MG Brazil., crmachad{at}icb.ufmg.br (E-mail)

Communicating editor: N. ARNHEIM

We have identified single-nucleotide polymorphisms (SNPs) inthe mismatch-repair gene TcMSH2 from Trypanosoma cruzi. Phylogeneticinferences based on the SNPs, confirmed by RFLP analysis of32 strains, showed three distinct haplogroups, denominated A,B, and C. Haplogroups A and C presented strong identity withthe previously described T. cruzi lineages I and II, respectively.A third haplogroup (B) was composed of strains presenting hybridcharacteristics. All strains from a haplogroup encoded the samespecific protein isoform, called, respectively, TcMHS2a, TcMHS2b,and TcMHS2c. The classification into haplogroups A, B, and Ccorrelated with variation in the efficiency of mismatch repairin these cells. When microsatellite loci of strains representativeof each haplogroup were analyzed after being cultured in thepresence of hydrogen peroxide, new microsatellite alleles weredefinitely seen in haplogroups B and C, while no evidence ofmicrosatellite instability was found in haplogroup A. Also,cells from haplogroups B and C were considerably more resistantto cisplatin treatment, a characteristic known to be conferredby deficiency of mismatch repair in eukaryotic cells. Altogether,our data suggest that strains belonging to haplogroups B andC may have decreased mismatch-repair ability when compared withstrains assigned to the haplogroup A lineage.

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