Genetic structure of Trypanosoma cruziin Colombia revealed by a High-throughput Nuclear Multilocus Sequence Typing (nMLST) approach

Abstract

BackgroundChagas disease is a systemic pathology caused by Trypanosoma cruzi. This parasite reveals remarkable genetic variability, evinced in six Discrete Typing Units (DTUs) named from T. cruzi I to T. cruzi VI (TcI to TcVI). Recently newly identified genotypes have emerged such as TcBat in Brazil, Colombia and Panama associated to anthropogenic bats. The genotype with the broadest geographical distribution is TcI, which has recently been associated to severe cardiomyopathies in Argentina and Colombia. Therefore, new studies unraveling the genetic structure and natural history of this DTU must be pursued.ResultsWe conducted a spatial and temporal analysis on 50 biological clones of T. cruzi I (TcI) isolated from humans with different clinical phenotypes, triatomine bugs and mammal reservoirs across three endemic regions for Chagas disease in Colombia. These clones were submitted to a nuclear Multilocus Sequence Typing (nMLST) analysis in order to elucidate its genetic diversity and clustering. After analyzing 13 nuclear housekeeping genes and obtaining a 5821 bp length alignment, we detected two robust genotypes within TcI henceforth named TcIDOM (associated to human infections) and a second cluster associated to peridomestic and sylvatic populations. Additionaly, we detected putative events of recombination and an intriguing lack of linkage disequilibrium.ConclusionsThese findings reinforce the emergence of an enigmatic domestic T. cruzi genotype (TcIDOM), and demonstrates the high frequency of recombination at nuclear level across natural populations of T. cruzi. Therefore, the need to pursue studies focused on the diferential virulence profiles of TcI strains. The biological and epidemiological implications of these findings are herein discussed.

Is Predominant Clonal Evolution a Common Evolutionary Adaptation to Parasitism in Pathogenic Parasitic Protozoa, Fungi, Bacteria, and Viruses?

“…As a matter of fact, the authors claim that the populations exhibit linkage equilibrium, whereas the p values for linkage analysis are 4 Â 10 À4 (LD test) and 0.037 (Ia index of association), hence quite significant. Moreover, the hypothesis of linkage equilibrium in this population is at odds with the presence of two clearly delimited near-clades (RD pattern) supported by significant bootstrap values (Ramírez et al, 2013). This bootstrap result illustrates the usefulness of the flexible phylogenetic approach based on the congruence criterion used in the framework of the near-clade model.…”

“…Moreover, constant positive Fis values are at odds with the HardyeWeinberg equilibrium inferred by the authors. One study inferring that recombination is frequent in TCI Colombian populations (Ramírez et al, 2013) is based on a strong misinterpretation. As a matter of fact, the authors claim that the populations exhibit linkage equilibrium, whereas the p values for linkage analysis are 4 Â 10 À4 (LD test) and 0.037 (Ia index of association), hence quite significant.…”

Untangling the transmission dynamics of primary and secondary vectors of Trypanosoma cruzi in Colombia: parasite infection, feeding sources and discrete typing units

“…The DTUs present associations with transmission cycles, geography, vector species and clinical manifestation to some extent [7–12]. The DTU with the broadest geographical distribution is TcI and due to its high genetic diversity has been divided into two genotypes, associated to domestic and sylvatic foci (TcIDom and Sylvatic TcI, respectively) [13–16]. …”

Response to Tibayrenc and Ayala: reproductive clonality in protozoan pathogens – truth or artefact?

“…We did not cite the 2013 article they mention that contained an error in a P ‐value interpretation (Ramírez et al . ); however, we accept that there was an error for which correction has been submitted.…”