Plasmodium falciparum:: Worldwide sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-2 (MSP-2)
Plasmodium falciparum:: Worldwide sequence diversity and evolution of the malaria vaccine candidate merozoite surface protein-2 (MSP-2)
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DOI：
10.1016/j.exppara.2006.05.003
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发表时间：
2007-01-01
影响因子：
2.1
通讯作者：
Hartl, Daniel L.
中科院分区：
文献类型：
--
作者：
Ferreira, Marcelo U.;Hartl, Daniel L.
我们通过分析来自各大洲的448个恶性疟原虫裂殖子表面蛋白-2(MSP-2)等位基因，研究了恶性疟原虫裂殖子表面蛋白-2(MSP-2)序列多样化的模式和可能的机制。恶性疟原虫是疟疾疫苗的主要二态候选抗原。我们描述了几个核苷酸替换、插入和缺失事件、移码突变和重复单位的增殖，这些都产生了在MSP-2等位基因中发现的非凡多样性。我们讨论了自然获得的类型和变异型特异性免疫所发挥的正选择在维持观察到的多态水平方面的作用，并认为这是在二态MSP-2结构域中发现显著过量的非同义核苷酸替换的最可能的解释。在少数(3.1%)分离株中观察到由不同二态类型的等位基因之间的减数分裂重组产生的杂交序列，其中大部分来自非洲。我们没有发现证据表明MSP-2基因座上的等位基因二态存在于恶性疟原虫物种形成之前的非常古老的起源，这与最近对其他表面疟疾抗原的发现形成了对比。(C)2006 Elsevier Inc.保留所有权利。
We examined patterns and putative mechanisms of sequence diversification in the merozoite surface protein-2 (MSP-2) of Plasmodium falciparum, a major dimorphic malaria vaccine candidate antigen, by analyzing 448 msp-2 alleles from all continents. We describe several nucleotide replacements, insertion and deletion events, frameshift mutations, and proliferations of repeat units that generate the extraordinary diversity found in msp-2 alleles. We discuss the role of positive selection exerted by naturally acquired type- and variant-specific immunity in maintaining the observed levels of polymorphism and suggest that this is the most likely explanation for the significant excess of nonsynonymous nucleotide replacements found in dimorphic msp-2 domains. Hybrid sequences created by meiotic recombination between alleles of different dimorphic types were observed in few (3.1%) isolates, mostly from Africa. We found no evidence for an extremely ancient origin of allelic dimorphism at the msp-2 locus, predating P. falciparum speciation, in contrast with recent findings for other surface malarial antigens. (c) 2006 Elsevier Inc. All rights reserved.