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Genomic diversity in Trypanosoma cruzi : Evolutionary and pathogenetic implications

Genomic diversity in Trypanosoma cruzi : Evolutionary and pathogenetic implications. Carlos Chagas 1879-1934. Charles Darwin 1809-1882. 1909. A parasitic disease One single parasite One single form of transmission (vectorial). 1909. One single form of transmission (vectorial).

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Genomic diversity in Trypanosoma cruzi : Evolutionary and pathogenetic implications

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  1. Genomic diversity in Trypanosoma cruzi : Evolutionary and pathogenetic implications

  2. Carlos Chagas 1879-1934

  3. Charles Darwin 1809-1882

  4. 1909 • A parasitic disease • One single parasite • One single form of transmission (vectorial)

  5. 1909 • One single form of transmission (vectorial)

  6. Ecobiology of Trypanosoma cruzi

  7. 1909 • One single parasite

  8. From Buscaglia & DiNoia (2003)

  9. Wedecided to perform a haplotypic studyof nuclear lineagemarkers, microsatellitesand mtDNA sequencevariation in 75 clonal strainsofTrypanosomacruziand to use theresults to establishthestructureof its geneticdiversityand to makeinferencesabout its evolutionarypast

  10. Microsatellites allele A allele B allele C AA AB AC BB BC CC

  11. Microsatellites • Abundant • Mutation rates ~10-3-10-4 • Multiallelic • High heterozygosity

  12. Dinucleotides 47,6% Trinucleotideo 38,6% Tetranucleotides 13,7% Aproximately 1% of the T. cruzi genome is made up of microssatellites

  13. etc.

  14. Conversão Gênica

  15. Quanta atividade sexual ocorreu no passado e ocorre hoje?

  16. 1 0 1 0 0 0 1 1 84 1 0 0 1 1 1 0 1 115 1 0 0 1 1 1 0 0 138 1 1 0 1 0 1 0 1 150 0 0 0 0 1 1 0 0 167 1 0 1 0 1 1 0 0 182 115 138 150 167 182 84 84 0 2 7 3 5 4 115 2 0 4 1 9 3 138 7 4 0 5 6 1 150 3 1 5 0 8 9 167 5 9 6 8 0 3 182 4 3 1 9 3 0 Allele sizes Clone alleles 84 267/269 FACTOR 115 273/279 138 267/271 150 259/259 167 263/277 182 269/273 MIX Matrix of genetic distances 75 clones 5 microsatellites MDS VisualizationofthedistancematrixwithMDS

  17. Cluster B T. cruzi IIc T. cruzi IIa Cluster BH T. cruzi IId + IIe Cluster C T. cruzi IIb Cluster A T. cruzi I

  18. Transform multilocal genotypes into haplotypes Input typing of microsatellitesand 25alpharDNA SNP Construct haplotypic network basedon the knownmutation models of themarkers 141haplotypes

  19. Haplogroup Y Haplogroup Z Haplogrupo I Haplogroup X

  20. Hybrids (DTU2e) DTU 2a T. cruzi I (DTU 1) T. cruziII(DTU2b) T. cruziII(DTU2b) T. cruzi III(DTU 2c) Hybrids (DTU2d)

  21. Wedecided to perform a haplotypic studyof nuclear lineagemarkers, microsatellitesandmtDNA sequencevariation in 75 clonal strainsofTrypanosomacruziand to use theresults to establishthestructureof its geneticdiversityand to makeinferencesabout its evolutionarypast

  22. ~300pb DNA sequencing in 41 T. cruzi strains COII

  23. CytB Brisse et al., 2003

  24. NADH1 Machado & Ayala, 2001

  25. MDS C MDS C MDS C T. cruzi II T. CruziIII / Hybrids T. cruzi I MDS B/BH MDS B/BH MDS A MDS B/BH MDS A MDS A

  26. Hybrids T. cruzi II T. cruzi III

  27. Westenberger et al, 2006

  28. 3 Haplogroups 3 Mitochondrial Haplogroups

  29. Variance of allele size in five microsatellites

  30. Locus MCLG10 T. cruzi I T. cruzi II T. cruzi III

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