Ferreira Marcelo U, Hartl Daniel L
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo (SP), Brazil.
Exp Parasitol. 2007 Jan;115(1):32-40. doi: 10.1016/j.exppara.2006.05.003. Epub 2006 Jun 21.
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.
我们通过分析来自各大洲的448个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（一种主要的双态疟疾疫苗候选抗原）中序列多样化的模式和可能机制。我们描述了几种核苷酸替换、插入和缺失事件、移码突变以及重复单元的增殖，这些导致了在MSP-2等位基因中发现的异常多样性。我们讨论了自然获得的类型特异性和变体特异性免疫所施加的正选择在维持观察到的多态性水平中的作用，并表明这是双态MSP-2结构域中非同义核苷酸替换显著过量的最可能解释。在少数（3.1%）分离株中观察到了由不同双态类型等位基因之间的减数分裂重组产生的杂交序列，这些分离株大多来自非洲。与其他疟疾表面抗原的最新发现相反，我们没有发现证据表明MSP-2位点的等位基因双态性起源极其古老，早于恶性疟原虫物种形成。
