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- Title
Recent, Independent and Anthropogenic Origins of Trypanosoma cruzi Hybrids.
- Authors
Lewis, Michael D.; Llewellyn, Martin S.; Yeo, Matthew; Acosta, Nidia; Gaunt, Michael W.; Miles, Michael A.
- 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. Author Summary: Trypanosoma cruzi is a parasite that causes Chagas disease in humans, an often fatal condition affecting at least 8 million people. The clinical outcome of Chagas disease is variable, which is probably partially attributable to genetic differences between T. cruzi strains. Differences between T. cruzi strains can arise by gradual accumulation of mutations in independent lineages (clonal reproduction) or by recombination between strains, which generates new combinations of existing alleles (sexual reproduction). Although sex has been observed experimentally, and epidemiologically important T. cruzi subgroups (TcV TcVI) originated via hybridisation events, active recombination is considered to be extremely rare. Our aim was to determine when recombination events have occurred during the evolution of T. cruzi. We analysed differences within and between T. cruzi subgroups in DNA sequences that evolve at different speeds. We found multiple recombination events, several of which were very recent in evolutionary terms. We show that TcV and TcVI most likely originated as a result of human activities that promoted mixing between subgroups, suggesting a continuing risk for emergence and spread of new genotypes generated by sexual reproduction. We also found evidence that sexual reproduction in T. cruzi could involve mechanisms different from those seen in multi-cellular eukaryotes.
- Subjects
TRYPANOSOMA cruzi; CLONE cells; LOCUS (Genetics); CHAGAS' disease; DNA sequencing; TRICHOMONIASIS
- Publication
PLoS Neglected Tropical Diseases, 2011, Vol 5, Issue 10, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0001363