The genome sequence of Trypanosoma brucei gambiense, causative agent of chronic Human African Trypanosomiasis

Jackson, A. et al. (2010) The genome sequence of Trypanosoma brucei gambiense, causative agent of chronic Human African Trypanosomiasis. PLoS Neglected Tropical Diseases, 4(4), e658. (doi:10.1371/journal.pntd.0000658) (PMID:20404998) (PMCID:PMC2854126)

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Abstract

<p><b>Background:</b> <i>Trypanosoma brucei gambiense</i> is the causative agent of chronic Human African Trypanosomiasis or sleeping sickness, a disease endemic across often poor and rural areas of Western and Central Africa. We have previously published the genome sequence of a <i>T. b. brucei</i> isolate, and have now employed a comparative genomics approach to understand the scale of genomic variation between <i>T. b. gambiense</i> and the reference genome. We sought to identify features that were uniquely associated with <i>T. b. gambiense</i> and its ability to infect humans.</p> <p><b>Methods and findings:</b> An improved high-quality draft genome sequence for the group 1 <i>T. b. gambiense</i> DAL 972 isolate was produced using a whole-genome shotgun strategy. Comparison with <i>T. b. brucei</i> showed that sequence identity averages 99.2% in coding regions, and gene order is largely collinear. However, variation associated with segmental duplications and tandem gene arrays suggests some reduction of functional repertoire in <i>T. b. gambiense</i> DAL 972. A comparison of the variant surface glycoproteins (VSG) in <i>T. b. brucei</i> with all <i>T. b. gambiense</i> sequence reads showed that the essential structural repertoire of VSG domains is conserved across <i>T. brucei</i>.</p> <p><b>Conclusions:</b> This study provides the first estimate of intraspecific genomic variation within <i>T. brucei</i>, and so has important consequences for future population genomics studies. We have shown that the <i>T. b. gambiense</i> genome corresponds closely with the reference, which should therefore be an effective scaffold for any <i>T. brucei</i> genome sequence data. As VSG repertoire is also well conserved, it may be feasible to describe the total diversity of variant antigens. While we describe several as yet uncharacterized gene families with predicted cell surface roles that were expanded in number in <i>T. b. brucei</i>, no <i>T. b. gambiense</i>-specific gene was identified outside of the subtelomeres that could explain the ability to infect humans.</p>

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:MacLeod, Professor Annette and Barry, Professor Dave and Capewell, Dr Paul
Authors: Jackson, A., Sanders, M., Berry, A., McQuillan, J., Aslett, M., Quail, M.A., Chukualim, B., Capewell, P., MacLeod, A., Melville, S., Gibson, W., Barry, J.D., Berriman, M., and Hertz-Fowler, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Copyright Holders:Copyright © 2010 Authors
First Published:First published in PLoS Neglected Tropical Diseases 4(4):e658
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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