title: Whole-genome sequencing of Trypanosoma brucei reveals introgression between subspecies that is associated with virulence.
abstract: Human African trypanosomiasis is caused by two subspecies of Trypanosoma brucei. Trypanosoma brucei rhodesiense is found in East Africa and frequently causes acute disease, while Trypanosoma brucei gambiense is found in West Africa and is associated with chronic disease. Samples taken from a single focus of a Ugandan outbreak of T. b. rhodesiense in the 1980s were associated with either chronic or acute disease. We sequenced the whole genomes of two of these isolates, which showed that they are genetically distinct from each other. Analysis of single nucleotide polymorphism markers in a panel of 31 Ugandan isolates plus 32 controls revealed a mixture of East African and West African haplotypes, and some of these haplotypes were associated with the different virulence phenotypes. It has been shown recently that T. b. brucei and T. b. rhodesiense populations undergo genetic exchange in natural populations. Our analysis showed that these strains from the Ugandan epidemic were intermediate between the reference genome sequences of T. b. gambiense and T. b. brucei and contained haplotypes that were present in both subspecies. This suggests that the human-infective subspecies of T. brucei are not genetically isolated, and our data are consistent with genomic introgression between East African and West African T. b. brucei subspecies. This has implications for the control of the parasite, the spread of drug resistance, and understanding the variation in virulence and the emergence of human infectivity.
  
  
  OBJECTIVE
  We present a genetic study of the acute form of "sleeping sickness" caused by the protozoan parasite Trypanosoma brucei rhodesiense from a single outbreak in Uganda. This represents an advance in our understanding of the relationship between the T. b. rhodesiense and Trypanosoma brucei gambiense subspecies that have previously been considered geographically distinct. Our data suggest that introgression of West African-derived T. brucei haplotypes may be associated with differences in disease presentation in the East African disease. These findings are not only of scientific interest but also important for parasite control, as they suggest that the human-infective T. brucei subspecies are not genetically isolated.
authors: Centre for Genomic Research, Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom.
authors: Ian
authors: I
authors: Goodhead
authors: Paul
authors: P
authors: Capewell
authors: J Wendi
authors: JW
authors: Bailey
authors: Tanja
authors: T
authors: Beament
authors: Michael
authors: M
authors: Chance
authors: Suzanne
authors: S
authors: Kay
authors: Sarah
authors: S
authors: Forrester
authors: Annette
authors: A
authors: MacLeod
authors: Mark
authors: M
authors: Taylor
authors: Harry
authors: H
authors: Noyes
authors: Neil
authors: N
authors: Hall
mesh_terms: D016054:DNA, Protozoan / Q000737:chemistry* / Q000235:genetics*; D004196:Disease Outbreaks; D018503:Genome, Protozoan; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D016833:Trypanosoma brucei rhodesiense / Q000235:genetics* / Q000302:isolation & purification; D014353:Trypanosomiasis, African / Q000469:parasitology; D014454:Uganda / Q000453:epidemiology; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics
chemical_list: D016054:DNA, Protozoan; D037521:Virulence Factors
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