title: Comparative genomics reveals multiple genetic backgrounds of human pathogenicity in the Trypanosoma brucei complex.
abstract: The Trypanosoma brucei complex contains a number of subspecies with exceptionally variable life histories, including zoonotic subspecies, which are causative agents of human African trypanosomiasis (HAT) in sub-Saharan Africa. Paradoxically, genomic variation between taxa is extremely low. We analyzed the whole-genome sequences of 39 isolates across the T. brucei complex from diverse hosts and regions, identifying 608,501 single nucleotide polymorphisms that represent 2.33% of the nuclear genome. We show that human pathogenicity occurs across a wide range of parasite genotypes, and taxonomic designation does not reflect genetic variation across the group, as previous studies have suggested based on a small number of genes. This genome-wide study allowed the identification of significant host and geographic location associations. Strong purifying selection was detected in genomic regions associated with cytoskeleton structure, and regulatory genes associated with antigenic variation, suggesting conservation of these regions in African trypanosomes. In agreement with expectations drawn from meiotic reciprocal recombination, differences in average linkage disequilibrium between chromosomes in T. brucei correlate positively with chromosome size. In addition to insights into the life history of a diverse group of eukaryotic parasites, the documentation of genomic variation across the T. brucei complex and its association with specific hosts and geographic localities will aid in the development of comprehensive monitoring tools crucial to the proposed elimination of HAT by 2020, and on a shorter term, for monitoring the feared merger between the two human infective parasites, T. brucei rhodesiense and T. b. gambiense, in northern Uganda.
authors.affiliation: Department of Ecology and Evolutionary Biology, Yale University mark.sistrom@yale.edu.
authors.forename: Mark
authors.initials: M
authors.lastname: Sistrom
authors.affiliation: Department of Ecology and Evolutionary Biology, Yale University.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Evans
authors.affiliation: Department of Computer Science, Yale University.
authors.forename: Robert
authors.initials: R
authors.lastname: Bjornson
authors.affiliation: School of Biological Sciences, University of Bristol, United Kingdom.
authors.forename: Wendy
authors.initials: W
authors.lastname: Gibson
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland Zoological Institute, University of Basel, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Balmer
authors.affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Mäser
authors.affiliation: Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT.
authors.forename: Serap
authors.initials: S
authors.lastname: Aksoy
authors.affiliation: Department of Ecology and Evolutionary Biology, Yale University.
authors.forename: Adalgisa
authors.initials: A
authors.lastname: Caccone
mesh_terms: D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D014346:Trypanosoma brucei brucei / Q000235:genetics / Q000472:pathogenicity*; D014774:Virulence / Q000235:genetics
keywords: comparative genomics; genomics; next gen sequencing; population genomics; trypanosomatids