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. 2003 May;164(1):117–126. doi: 10.1093/genetics/164.1.117

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 1, Santuza M R Teixeira 1, Sérgio D J Pena 1, Carlos Renato Machado 1
PMCID: PMC1462559  PMID: 12750325

Abstract

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.

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Selected References

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  1. Augusto-Pinto L., Bartholomeu D. C., Teixeira S. M., Pena S. D., Machado C. R. Molecular cloning and characterization of the DNA mismatch repair gene class 2 from the Trypanosoma cruzi. Gene. 2001 Jul 11;272(1-2):323–333. doi: 10.1016/s0378-1119(01)00549-2. [DOI] [PubMed] [Google Scholar]
  2. Ban C., Yang W. Structural basis for MutH activation in E.coli mismatch repair and relationship of MutH to restriction endonucleases. EMBO J. 1998 Mar 2;17(5):1526–1534. doi: 10.1093/emboj/17.5.1526. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Claij Nanna, Te Riele Hein. Methylation tolerance in mismatch repair proficient cells with low MSH2 protein level. Oncogene. 2002 Apr 25;21(18):2873–2879. doi: 10.1038/sj.onc.1205395. [DOI] [PubMed] [Google Scholar]
  4. Corpet F. Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 1988 Nov 25;16(22):10881–10890. doi: 10.1093/nar/16.22.10881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Degtyareva Natasha P., Greenwell Patricia, Hofmann E. Randal, Hengartner Michael O., Zhang Lijia, Culotti Joseph G., Petes Thomas D. Caenorhabditis elegans DNA mismatch repair gene msh-2 is required for microsatellite stability and maintenance of genome integrity. Proc Natl Acad Sci U S A. 2002 Feb 5;99(4):2158–2163. doi: 10.1073/pnas.032671599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Denamur E., Lecointre G., Darlu P., Tenaillon O., Acquaviva C., Sayada C., Sunjevaric I., Rothstein R., Elion J., Taddei F. Evolutionary implications of the frequent horizontal transfer of mismatch repair genes. Cell. 2000 Nov 22;103(5):711–721. doi: 10.1016/s0092-8674(00)00175-6. [DOI] [PubMed] [Google Scholar]
  7. Di Noia Javier M., Buscaglia Carlos A., De Marchi Claudia R., Almeida Igor C., Frasch Alberto C. C. A Trypanosoma cruzi small surface molecule provides the first immunological evidence that Chagas' disease is due to a single parasite lineage. J Exp Med. 2002 Feb 18;195(4):401–413. doi: 10.1084/jem.20011433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Drotschmann K., Clark A. B., Tran H. T., Resnick M. A., Gordenin D. A., Kunkel T. A. Mutator phenotypes of yeast strains heterozygous for mutations in the MSH2 gene. Proc Natl Acad Sci U S A. 1999 Mar 16;96(6):2970–2975. doi: 10.1073/pnas.96.6.2970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fishel R., Lescoe M. K., Rao M. R., Copeland N. G., Jenkins N. A., Garber J., Kane M., Kolodner R. The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell. 1993 Dec 3;75(5):1027–1038. doi: 10.1016/0092-8674(93)90546-3. [DOI] [PubMed] [Google Scholar]
  10. Fujieda S., Tanaka N., Sunaga H., Noda I., Sugimoto C., Tsuzuki H., Saito H. Expression of hMSH2 correlates with in vitro chemosensitivity to CDDP cytotoxicity in oral and oropharyngeal carcinoma. Cancer Lett. 1998 Oct 23;132(1-2):37–44. doi: 10.1016/s0304-3835(98)00157-8. [DOI] [PubMed] [Google Scholar]
  11. Gaunt M., Miles M. The ecotopes and evolution of triatomine bugs (triatominae) and their associated trypanosomes. Mem Inst Oswaldo Cruz. 2000 Jul-Aug;95(4):557–565. doi: 10.1590/s0074-02762000000400019. [DOI] [PubMed] [Google Scholar]
  12. Hasegawa M., Kishino H., Yano T. Dating of the human-ape splitting by a molecular clock of mitochondrial DNA. J Mol Evol. 1985;22(2):160–174. doi: 10.1007/BF02101694. [DOI] [PubMed] [Google Scholar]
  13. Hsieh P. Molecular mechanisms of DNA mismatch repair. Mutat Res. 2001 Jul 12;486(2):71–87. doi: 10.1016/s0921-8777(01)00088-x. [DOI] [PubMed] [Google Scholar]
  14. Jackson A. L., Chen R., Loeb L. A. Induction of microsatellite instability by oxidative DNA damage. Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12468–12473. doi: 10.1073/pnas.95.21.12468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Jackson A. L., Loeb L. A. Microsatellite instability induced by hydrogen peroxide in Escherichia coli. Mutat Res. 2000 Feb 14;447(2):187–198. doi: 10.1016/s0027-5107(99)00206-7. [DOI] [PubMed] [Google Scholar]
  16. Kimura M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 1980 Dec;16(2):111–120. doi: 10.1007/BF01731581. [DOI] [PubMed] [Google Scholar]
  17. Levinson G., Gutman G. A. High frequencies of short frameshifts in poly-CA/TG tandem repeats borne by bacteriophage M13 in Escherichia coli K-12. Nucleic Acids Res. 1987 Jul 10;15(13):5323–5338. doi: 10.1093/nar/15.13.5323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Macedo A. M., Martins M. S., Chiari E., Pena S. D. DNA fingerprinting of Trypanosoma cruzi: a new tool for characterization of strains and clones. Mol Biochem Parasitol. 1992 Oct;55(1-2):147–153. doi: 10.1016/0166-6851(92)90135-7. [DOI] [PubMed] [Google Scholar]
  19. Macedo A. M., Pimenta J. R., Aguiar R. S., Melo A. I., Chiari E., Zingales B., Pena S. D., Oliveira R. P. Usefulness of microsatellite typing in population genetic studies of Trypanosoma cruzi. Mem Inst Oswaldo Cruz. 2001 Apr;96(3):407–413. doi: 10.1590/s0074-02762001000300023. [DOI] [PubMed] [Google Scholar]
  20. Machado C. A., Ayala F. J. Nucleotide sequences provide evidence of genetic exchange among distantly related lineages of Trypanosoma cruzi. Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7396–7401. doi: 10.1073/pnas.121187198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Machado Carlos A., Ayala Francisco J. Sequence variation in the dihydrofolate reductase-thymidylate synthase (DHFR-TS) and trypanothione reductase (TR) genes of Trypanosoma cruzi. Mol Biochem Parasitol. 2002 Apr 30;121(1):33–47. doi: 10.1016/s0166-6851(02)00019-1. [DOI] [PubMed] [Google Scholar]
  22. Mayer Frank, Gillis Ad J. M., Dinjens Winand, Oosterhuis J. Wolter, Bokemeyer Carsten, Looijenga Leendert H. J. Microsatellite instability of germ cell tumors is associated with resistance to systemic treatment. Cancer Res. 2002 May 15;62(10):2758–2760. [PubMed] [Google Scholar]
  23. Miles M. A., Povoa M. M., de Souza A. A., Lainson R., Shaw J. J., Ketteridge D. S. Chagas's disease in the Amazon Basin: Ii. The distribution of Trypanosoma cruzi zymodemes 1 and 3 in Pará State, north Brazil. Trans R Soc Trop Med Hyg. 1981;75(5):667–674. doi: 10.1016/0035-9203(81)90145-0. [DOI] [PubMed] [Google Scholar]
  24. Miles M. A., Souza A., Povoa M., Shaw J. J., Lainson R., Toye P. J. Isozymic heterogeneity of Trypanosoma cruzi in the first autochthonous patients with Chagas' disease in Amazonian Brazil. Nature. 1978 Apr 27;272(5656):819–821. doi: 10.1038/272819a0. [DOI] [PubMed] [Google Scholar]
  25. Momen H. Taxonomy of Trypanosoma cruzi: a commentary on characterization and nomenclature. Mem Inst Oswaldo Cruz. 1999;94 (Suppl 1):181–184. doi: 10.1590/s0074-02761999000700025. [DOI] [PubMed] [Google Scholar]
  26. Obmolova G., Ban C., Hsieh P., Yang W. Crystal structures of mismatch repair protein MutS and its complex with a substrate DNA. Nature. 2000 Oct 12;407(6805):703–710. doi: 10.1038/35037509. [DOI] [PubMed] [Google Scholar]
  27. Oliveira R. P., Broude N. E., Macedo A. M., Cantor C. R., Smith C. L., Pena S. D. Probing the genetic population structure of Trypanosoma cruzi with polymorphic microsatellites. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3776–3780. doi: 10.1073/pnas.95.7.3776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Oliveira R. P., Melo A. I., Macedo A. M., Chiari E., Pena S. D. The population structure of Trypanosoma cruzi: expanded analysis of 54 strains using eight polymorphic CA-repeat microsatellites. Mem Inst Oswaldo Cruz. 1999;94 (Suppl 1):65–70. doi: 10.1590/s0074-02761999000700006. [DOI] [PubMed] [Google Scholar]
  29. Saitou N., Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. doi: 10.1093/oxfordjournals.molbev.a040454. [DOI] [PubMed] [Google Scholar]
  30. Schofield C. Trypanosoma cruzi - the vector-parasite paradox. Mem Inst Oswaldo Cruz. 2000 Jul-Aug;95(4):535–544. doi: 10.1590/s0074-02762000000400016. [DOI] [PubMed] [Google Scholar]
  31. Souto R. P., Fernandes O., Macedo A. M., Campbell D. A., Zingales B. DNA markers define two major phylogenetic lineages of Trypanosoma cruzi. Mol Biochem Parasitol. 1996 Dec 20;83(2):141–152. doi: 10.1016/s0166-6851(96)02755-7. [DOI] [PubMed] [Google Scholar]
  32. Vaisman A., Varchenko M., Umar A., Kunkel T. A., Risinger J. I., Barrett J. C., Hamilton T. C., Chaney S. G. The role of hMLH1, hMSH3, and hMSH6 defects in cisplatin and oxaliplatin resistance: correlation with replicative bypass of platinum-DNA adducts. Cancer Res. 1998 Aug 15;58(16):3579–3585. [PubMed] [Google Scholar]
  33. Zdraveski Zoran Z., Mello Jill A., Farinelli Christine K., Essigmann John M., Marinus Martin G. MutS preferentially recognizes cisplatin- over oxaliplatin-modified DNA. J Biol Chem. 2001 Nov 8;277(2):1255–1260. doi: 10.1074/jbc.M105382200. [DOI] [PubMed] [Google Scholar]
  34. Zienolddiny S., Ryberg D., Haugen A. Induction of microsatellite mutations by oxidative agents in human lung cancer cell lines. Carcinogenesis. 2000 Aug;21(8):1521–1526. [PubMed] [Google Scholar]

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