Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications.
Independent Origin and Global Distribution of Distinct Plasmodium vivax Duffy Binding Protein Gene Duplications.
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DOI：
10.1371/journal.pntd.0005091
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发表时间：
2016-10
影响因子：
3.8
通讯作者：
Rayner JC
中科院分区：
文献类型：
--
作者：
Hostetler JB;Lo E;Kanjee U;Amaratunga C;Suon S;Sreng S;Mao S;Yewhalaw D;Mascarenhas A;Kwiatkowski DP;Ferreira MU;Rathod PK;Yan G;Fairhurst RM;Duraisingh MT;Rayner JC
间日疟原虫是非洲以外大多数疟疾发作的原因，但仍是一种研究相对较少的病原体。间日疟原虫感染的病理学在很大程度上依赖于这种寄生虫识别和入侵人类红细胞的能力。这种侵袭过程涉及裂殖子中间日疟原虫Duffy结合蛋白(PvDBP)和红细胞表面趋化因子Duffy抗原受体(DARC)之间的相互作用。临床分离株的全基因组测序最近证实，一些间日疟原虫基因组包含两个拷贝的PvDBP基因。这种复制的频率在马达加斯加特别高，那里也有证据表明DARC阴性的人感染了间日疟原虫。这种重复的功能意义和全球流行率，以及PvDBP基因座是否存在其他拷贝数变异，尚不清楚。利用全基因组测序和聚合酶链式反应对间日疟原虫临床分离株的PvDBP基因座进行研究，发现PvDBP基因重复在柬埔寨普遍存在。柬埔寨PvDBP重复的边界与马达加斯加以前发现的边界不同，这意味着目前的分子分析无法检测到它。柬埔寨的PvDBP重复与寄生虫密度或DARC基因无关，在柬埔寨的四个年度传播季节中的患病率从20%到38%不等。这种复制在来自巴西和埃塞俄比亚的间日疟原虫分离株中也存在，但在印度没有。PvDBP的复制比之前认为的要广泛得多，也更复杂，至少有两个不同的复制在全球流通。在来自三大洲的寄生虫中发现了相同的复制边界，并在基本上不存在DARC阴性的人群中发现了高流行率。因此，PvDBP复制不太可能与DARC阴性个体的感染有关，但需要进行功能测试来证实这一假设。疟疾寄生虫必须能够适应，以逃避人类免疫系统，并成功地将自己传播给不同的人。这种适应性的关键是疟疾寄生虫基因组高度可变，包含从DNA序列的简单微小变化到单个基因拷贝数的复杂大规模变化的各种突变。最近，人们发现间日疟原虫的一些样本复制了编码Duffy结合蛋白的基因，这种蛋白使间日疟原虫能够识别和入侵人类红细胞。间日疟原虫是导致非洲以外大多数疟疾发作的寄生虫。通过对柬埔寨间日疟患者寄生虫的研究，我们发现实际上存在两种不同类型的基因复制，本研究中发现的新复制类型存在于所测试的柬埔寨间日疟原虫分离株的20%至38%中。在巴西和埃塞俄比亚间日疟患者的寄生虫中也发现了相同的基因重复，这表明该基因的变异比之前认为的更复杂和常见。这两个基因重复的功能意义和来源有待进一步研究。
Plasmodium vivax causes the majority of malaria episodes outside Africa, but remains a relatively understudied pathogen. The pathology of P. vivax infection depends critically on the parasite’s ability to recognize and invade human erythrocytes. This invasion process involves an interaction between P. vivax Duffy Binding Protein (PvDBP) in merozoites and the Duffy antigen receptor for chemokines (DARC) on the erythrocyte surface. Whole-genome sequencing of clinical isolates recently established that some P. vivax genomes contain two copies of the PvDBP gene. The frequency of this duplication is particularly high in Madagascar, where there is also evidence for P. vivax infection in DARC-negative individuals. The functional significance and global prevalence of this duplication, and whether there are other copy number variations at the PvDBP locus, is unknown. Using whole-genome sequencing and PCR to study the PvDBP locus in P. vivax clinical isolates, we found that PvDBP duplication is widespread in Cambodia. The boundaries of the Cambodian PvDBP duplication differ from those previously identified in Madagascar, meaning that current molecular assays were unable to detect it. The Cambodian PvDBP duplication did not associate with parasite density or DARC genotype, and ranged in prevalence from 20% to 38% over four annual transmission seasons in Cambodia. This duplication was also present in P. vivax isolates from Brazil and Ethiopia, but not India. PvDBP duplications are much more widespread and complex than previously thought, and at least two distinct duplications are circulating globally. The same duplication boundaries were identified in parasites from three continents, and were found at high prevalence in human populations where DARC-negativity is essentially absent. It is therefore unlikely that PvDBP duplication is associated with infection of DARC-negative individuals, but functional tests will be required to confirm this hypothesis. Malaria parasites must be adaptable to evade the human immune system and successfully transmit themselves to different individuals. Key to this adaptability is the fact that malaria parasite genomes are highly variable, containing mutations ranging from simple small changes in DNA sequence to complex large-scale changes in the number of copies of individual genes. Some samples of Plasmodium vivax, the parasite that causes most malaria episodes outside Africa, have recently been found to have duplicated the gene encoding Duffy Binding Protein, which enables P. vivax parasites to recognize and invade human red blood cells. By studying parasites from Cambodian patients with P. vivax malaria, we have discovered that there are actually two different types of gene duplication, with the new duplication type identified in this study present in 20% to 38% of Cambodian P. vivax isolates tested. The same gene duplication was also found in parasites from Brazilian and Ethiopian patients with P. vivax malaria, suggesting that variation in this gene is more complex and common than previously thought. The functional significance and origin of these two gene duplications requires further study.
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影响因子：
64.8
作者：
Carlton, Jane M.;Adams, John H.;Silva, Joana C.;Bidwell, Shelby L.;Lorenzi, Hernan;Caler, Elisabet;Crabtree, Jonathan;Angiuoli, Samuel V.;Merino, Emilio F.;Amedeo, Paolo;Cheng, Qin;Coulson, Richard M. R.;Crabb, Brendan S.;del Portillo, Hernando A.;Essien, Kobby;Feldblyum, Tamara V.;Fernandez-Becerra, Carmen;Gilson, Paul R.;Gueye, Amy H.;Guo, Xiang;Kang'a, Simon;Kooij, Taco W. A.;Korsinczky, Michael;Meyer, Esmeralda V. -S.;Nene, Vish;Paulsen, Ian;White, Owen;Ralph, Stuart A.;Ren, Qinghu;Sargeant, Tobias J.;Salzberg, Steven L.;Stoeckert, Christian J.;Sullivan, Steven A.;Yamamoto, Marcio M.;Hoffman, Stephen L.;Wortman, Jennifer R.;Gardner, Malcolm J.;Galinski, Mary R.;Barnwell, John W.;Fraser-Liggett, Claire M.
通讯作者：
Fraser-Liggett, Claire M.
影响因子：
9.3
作者：
Cutts JC;Powell R;Agius PA;Beeson JG;Simpson JA;Fowkes FJ
通讯作者：
Fowkes FJ
影响因子：
3.8
作者：
Hostetler JB;Sharma S;Bartholdson SJ;Wright GJ;Fairhurst RM;Rayner JC
通讯作者：
Rayner JC
影响因子：
6.4
作者：
Betuela, Inoni;Rosanas-Urgell, Anna;Mueller, Ivo
通讯作者：
Mueller, Ivo
影响因子：
7
作者：
Bushell, K. Mark;Sollner, Christian;Wright, Gavin J.
通讯作者：
Wright, Gavin J.