Whole-genome sequencing of Trypanosoma brucei reveals introgression between subspecies that is associated with virulence.
Whole-genome sequencing of Trypanosoma brucei reveals introgression between subspecies that is associated with virulence.
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DOI：
10.1128/mbio.00197-13
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发表时间：
2013-08-20
期刊：
影响因子：
6.4
通讯作者：
Hall N
中科院分区：
文献类型：
--
作者：
Goodhead I;Capewell P;Bailey JW;Beament T;Chance M;Kay S;Forrester S;MacLeod A;Taylor M;Noyes H;Hall N
人类非洲锥虫病由布氏锥虫的两个亚种引起。布氏罗得西亚锥虫在东非发现，经常引起急性疾病，而布氏冈比亚锥虫在西非发现，与慢性疾病有关。20世纪80年代，从乌干达罗德西亚B型结核病暴发的一个疫源地采集的样本与慢性或急性疾病有关。我们对其中两个分离株的全基因组进行了测序，结果表明它们在遗传上彼此不同。单核苷酸多态性标记在一个小组的31个乌干达分离物加32个对照分析显示东非和西非单倍型的混合物，其中一些单倍型与不同的毒力表型。最近的研究表明，布氏锥虫和罗得西亚锥虫在自然群体中发生了遗传交换。我们的分析表明，这些来自乌干达疫情的菌株介于冈比亚锥虫B. gambiense和布氏锥虫B. brucei的参考基因组序列之间，并且包含存在于两个亚种中的单倍型。这表明人类感染的布氏锥虫亚种不是遗传隔离的，我们的数据与东非和西非布氏锥虫B亚种之间的基因组渐渗一致。这对寄生虫的控制、耐药性的传播以及了解毒力变异和人类传染性的出现具有影响。我们提出了一个遗传研究的急性形式的“昏睡病”所造成的原生动物寄生虫布氏锥虫罗得西亚从一个单一的爆发在乌干达。这代表了我们对T. B. rhodesiense和Trypanosoma brucei gambiense亚种之间关系的理解的进步，这些亚种以前被认为是地理上不同的。我们的数据表明，西非来源的布氏锥虫单倍型的基因渗入可能与东非疾病中疾病表现的差异有关。这些发现不仅具有科学意义，而且对寄生虫控制也很重要，因为它们表明人类感染的布氏锥虫亚种不是遗传隔离的。
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. 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.