Abstract
Trypanosoma cruzi, the etiological agent of Chagas disease, is highly genetically diverse. Numerous lines of evidence point to the existence of six stable genetic lineages or DTUs: TcI, TcIIa, TcIIb, TcIIc, TcIId, and TcIIe. Molecular dating suggests that T. cruzi is likely to have been an endemic infection of neotropical mammalian fauna for many millions of years. Here we have applied a panel of 49 polymorphic microsatellite markers developed from the online T. cruzi genome to document genetic diversity among 53 isolates belonging to TcIIc, a lineage so far recorded almost exclusively in silvatic transmission cycles but increasingly a potential source of human infection. These data are complemented by parallel analysis of sequence variation in a fragment of the glucose-6-phosphate isomerase gene. New isolates confirm that TcIIc is associated with terrestrial transmission cycles and armadillo reservoir hosts, and demonstrate that TcIIc is far more widespread than previously thought, with a distribution at least from Western Venezuela to the Argentine Chaco. We show that TcIIc is truly a discrete T. cruzi lineage, that it could have an ancient origin and that diversity occurs within the terrestrial niche independently of the host species. We also show that spatial structure among TcIIc isolates from its principal host, the armadillo Dasypus novemcinctus, is greater than that among TcI from Didelphis spp. opossums and link this observation to differences in ecology of their respective niches. Homozygosity in TcIIc populations and some linkage indices indicate the possibility of recombination but cannot yet be effectively discriminated from a high genome-wide frequency of gene conversion. Finally, we suggest that the derived TcIIc population genetic data have a vital role in determining the origin of the epidemiologically important hybrid lineages TcIId and TcIIe.
Highlights
At least 10 million people are thought to carry the infectious agent of Chagas disease, Trypanosoma cruzi, which is considered to be responsible for,13,000 deaths annually
Six major genetic lineages of the parasite have been identified with differential geographic distributions, ecological associations and epidemiological importance
With the advent of the T. cruzi genome sequence, it is possible to examine the micro-epidemiology of T. cruzi using high resolution genetic markers that assess diversity within these major types
Summary
At least 10 million people are thought to carry the infectious agent of Chagas disease, Trypanosoma cruzi, which is considered to be responsible for ,13,000 deaths annually (www.who.int, [1]). Domestic transmission is limited to Central and South America where domiciliated vector species occur. Consistent with an ancient association with South America [3] T. cruzi populations are highly diverse, with at least six stable discrete typing units (DTUs) reported: TcI, TcIIa, TcIIb, TcIIIc, TcIId, and TcIIe. Among these, TcI and TcIIb are the most divergent groups in molecular terms - estimates based on nuclear genes date their most recent common ancestor at 3–10 million years ago (MYA) [4]. Based on mosaic patterns of nucleotide diversity across nine nuclear genes, Westenberger et al, (2005) proposed that both are the product of an early hybridisation event(s) between lineages TcI and TcIIb [6]. Nuclear gene sequences consistently support their status as genetically separate clades [4,6,7,8] and flow cytometric analysis
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