Recent, Independent and Anthropogenic Origins of Trypanosoma cruzi Hybrids

Abstract

The single celled eukaryote Trypanosoma cruzi, a parasite transmitted by numerous species of triatomine bug in the Americas, causes Chagas disease in humans. T. cruzi generally reproduces asexually and appears to have a clonal population structure. However, two of the six major circulating genetic lineages, TcV and TcVI, are TcII-TcIII inter-lineage hybrids that are frequently isolated from humans in regions where chronic Chagas disease is particularly severe. Nevertheless, a prevalent view is that hybridisation events in T. cruzi were evolutionarily ancient and that active recombination is of little epidemiological importance. We analysed genotypes of hybrid and non-hybrid T. cruzi strains for markers representing three distinct evolutionary rates: nuclear GPI sequences (n = 88), mitochondrial COII-ND1 sequences (n = 107) and 28 polymorphic microsatellite loci (n = 35). Using Maximum Likelihood and Bayesian phylogenetic approaches we dated key evolutionary events in the T. cruzi clade including the emergence of hybrid lineages TcV and TcVI, which we estimated to have occurred within the last 60,000 years. We also found evidence for recent genetic exchange between TcIII and TcIV and between TcI and TcIV. These findings show that evolution of novel recombinants remains a potential epidemiological risk. The clearly distinguishable microsatellite genotypes of TcV and TcVI were highly heterozygous and displayed minimal intra-lineage diversity indicative of even earlier origins than sequence-based estimates. Natural hybrid genotypes resembled typical meiotic F1 progeny, however, evidence for mitochondrial introgression, absence of haploid forms and previous experimental crosses indicate that sexual reproduction in T. cruzi may involve alternatives to canonical meiosis. Overall, the data support two independent hybridisation events between TcII and TcIII and a recent, rapid spread of the hybrid progeny in domestic transmission cycles concomitant with, or as a result of, disruption of natural transmission cycles by human activities.

Ecological host fitting of Trypanosoma cruzi TcI in Bolivia: mosaic population structure, hybridization and a role for humans in Andean parasite dispersal

“…Trafficking of genetically homogeneous, human‐infective (at least in Cochabamba), highland TcI clones is reminiscent of the epidemic propagation of hybrid T. cruzi lineages TcV and TcVI by domestic T. infestans across the Southern Cone (Lewis et al . 2011). All highland study sites coincided with major, densely populated, transport routes transecting the departments of Cochabamba and Potosí and the distribution of highland strains closely reflected human migratory movements.…”

Reproductive clonality of pathogens: A perspective on pathogenic viruses, bacteria, fungi, and parasitic protozoa

“…Whatever the ecosystem considered, T. cruzi populations always display strong LD (1-3, 158, 194), involving different genetic markers (151,158,159). Its subdivision into six stable near-clades or DTUs (191) has been corroborated (149,152,160,161). Additional subdivisions can be evidenced by high-resolution markers (154,157).…”

“…In T. cruzi, it is remarkable that hybrid genotypes stabilized by clonal evolution have become superspreaders in humans in the southern range of Chagas disease (102,152,156,161,194). A similar state of affairs may be the case in Giardia (98), Leishmania (102,111,194,216), Perkinsus (119), Toxoplasma (134,136,139,207), C. neoformans (89), P. andina (91), and S. aureus (70).…”

The crucial role of the Instituto Evandro Chagas in Chagas disease research

“…The aim was to obtain a deeper understanding of the molecular epidemiology of Chagas disease and the extent and implications of genetic exchange in T. cruzi. The international collaborators produced a large body of relevant published work, and an assessment of the wider geographical distributions and ecological associations of the six genetic lineages of T. cruzi 26,27,28,29,30,31,32,33,34 ( Figure 7). Most recently, this work has included the development of peptide-based T. cruzi lineage-specific serology for discovery of the reservoir hosts of TcII, TcV and TcVI 35,36 .…”

“…Most recently, this work has included the development of peptide-based T. cruzi lineage-specific serology for discovery of the reservoir hosts of TcII, TcV and TcVI 35,36 . This later research is beyond the scope of the current text but updates can be found in key recent reviews or by searches with appropriate keywords in PubMed [26][27][28][29][30][31][32][33][34] . Although the IEC was not directly involved in ChagasEpiNet, it was the research at the IEC, in conjunction with subsequent developments in molecular technologies that provided the platform for the productive ChagasEpiNet international initiative.…”