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恶性疟原虫亚马逊分离株中疟疾疫苗候选物裂殖子表面蛋白-2(MSP-2)序列多样性的起源

Origins of sequence diversity in the malaria vaccine candidate merozoite surface protein-2 (MSP-2) in Amazonian isolates of Plasmodium falciparum.

作者信息

Hoffmann Erika H E, Malafronte Rosely S, Moraes-Avila Sandra L, Osakabe Ana Lúcia, Wunderlich Gerhard, Durham Alan M, Ribolla Paulo Eduardo M, del Portillo Hernando A, Ferreira Marcelo U

机构信息

Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 1374, 05508-900 São Paulo (SP), Brazil.

出版信息

Gene. 2006 Jul 19;376(2):224-30. doi: 10.1016/j.gene.2006.03.011. Epub 2006 Apr 5.

DOI:10.1016/j.gene.2006.03.011
PMID:16716539
Abstract

The recent evolution of Plasmodium falciparum is at odds with the extensive polymorphism found in most genes coding for antigens. Here, we examined the patterns and putative mechanisms of sequence diversification in the merozoite surface protein-2 (MSP-2), a major malarial repetitive surface antigen. We compared the msp-2 gene sequences from closely related clones derived from sympatric parasite isolates from Brazilian Amazonia and used microsatellite typing to examine, in these same clones, the haplotype background of chromosome 2, where msp-2 is located. We found examples of msp-2 sequence rearrangements putatively created by nonreciprocal recombinational events, such as replication slippage and gene conversion, while maintaining the chromosome haplotype. We conclude that these nonreciprocal recombination events may represent a major source of antigenic diversity in MSP-2 in P. falciparum populations with low rates of classical meiotic recombination.

摘要

恶性疟原虫的近期进化与大多数编码抗原的基因中发现的广泛多态性不一致。在这里,我们研究了裂殖子表面蛋白-2(MSP-2)(一种主要的疟疾重复性表面抗原)序列多样化的模式和推定机制。我们比较了来自巴西亚马逊地区同域寄生虫分离株的密切相关克隆的msp-2基因序列,并使用微卫星分型来检查这些相同克隆中msp-2所在的2号染色体的单倍型背景。我们发现了msp-2序列重排的例子,这些重排可能是由非相互重组事件(如复制滑移和基因转换)产生的,同时保持了染色体单倍型。我们得出结论,在经典减数分裂重组率较低的恶性疟原虫种群中,这些非相互重组事件可能是MSP-2抗原多样性的主要来源。

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