Comparative genomics reveals multiple genetic backgrounds of human pathogenicity in the Trypanosoma brucei complex.
Comparative genomics reveals multiple genetic backgrounds of human pathogenicity in the Trypanosoma brucei complex.
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DOI：
10.1093/gbe/evu222
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发表时间：
2014-10-05
影响因子：
3.3
通讯作者：
Caccone A
中科院分区：
文献类型：
--
作者：
Sistrom M;Evans B;Bjornson R;Gibson W;Balmer O;Mäser P;Aksoy S;Caccone A
布鲁氏锥虫复合体包含许多具有异常可变生活史的亚种，包括人畜共患亚种，它们是撒哈拉以南非洲人类非洲锥虫病（HAT）的病原体。矛盾的是，分类群之间的基因组变异极低。我们分析了来自不同宿主和地区的39株布鲁氏体复合体的全基因组序列，鉴定出608,501个单核苷酸多态性，占核基因组的2.33%。我们表明，人类致病性发生在广泛的寄生虫基因型中，而分类命名并不反映整个群体的遗传变异，正如以前的研究基于少数基因所表明的那样。这项全基因组研究允许鉴定重要的宿主和地理位置关联。在与细胞骨架结构相关的基因组区域和与抗原变异相关的调控基因中检测到强烈的纯化选择，表明这些区域在非洲锥虫中具有保守性。与从减数分裂互反重组中得出的预期一致，布氏体染色体间平均连锁不平衡的差异与染色体大小呈正相关。除了深入了解多种真核寄生虫的生活史之外，记录布鲁氏弓形体复合体的基因组变异及其与特定宿主和地理位置的关联，将有助于开发全面监测工具，这对于到2020年消除HAT的提议至关重要，并且在较短期内，用于监测乌干达北部两种人类感染性寄生虫——布氏罗得西亚弓形体和冈比亚弓形体——之间令人担忧的合并。
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.