Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus
Mosaic organization and heterogeneity in frequency of allelic recombination of the Plasmodium vivax merozoite surface protein-1 locus
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DOI：
10.1073/pnas.252348999
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发表时间：
2002-12-10
影响因子：
11.1
通讯作者：
Tanabe, K
中科院分区：
文献类型：
--
作者：
Putaporntip, C;Jongwutiwes, S;Tanabe, K
在来自不同地理区域的 40 个分离株的完整核苷酸序列中，对最广泛流行的人类疟疾寄生虫——间日疟原虫 (PvMsp-1) 的裂殖子表面蛋白 1 基因的组织和等位基因重组进行了评估。 31 个不同等位基因的比对揭示了 PvMsp-1 的镶嵌组织，由 7 个等位基因间保守块组成，两侧是 6 个可变块。可变块显示重复和非重复独特序列的广泛变化。 PvMsp-1中分布有大量重组位点，无论是保守区还是可变区独特序列，且分布不均匀。亚洲 PvMsp-1 等位基因的杂合性 (0.953 +/- 0.009) 高于巴西 (0.813 +/- 0.047)。亚洲和巴西之间不存在相同的等位基因，而在巴西发现的除了一个可变块非重复序列之外的所有等位基因都发生在亚洲。这些观察结果表明亚洲间日疟原虫种群是巴西种群的祖先，并且 PvMsp-1 在等位基因重组事件的频率方面具有异质性。随着核苷酸距离的增加，同义位点对之间的连锁不平衡迅速下降，支持重复重组事件导致新的 PvMsp-1 等位基因的反复起源，在来自泰国的间日疟原虫群体中，距离超过 3 kb 的连锁不平衡很少，这证明了寄生虫的有效高重组率。与此同时，在编码候选疫苗裂殖子表面蛋白-1 的 19-kDa C 端表皮生长因子样结构域的区域中，核苷酸多样性大大降低。
The organization and allelic recombination of the merozoite surface protein-1 gene of Plasmodium vivax (PvMsp-1), the most widely prevalent human malaria parasite, were evaluated in complete nucleotide sequences of 40 isolates from various geographic areas. Alignment of 31 distinct alleles revealed the mosaic organization of PvMsp-1, consisting of seven interallele conserved blocks flanked by six variable blocks. The variable blocks showed extensive variation in repeats and nonrepeat unique sequences. Numerous recombination sites were distributed throughout PvMsp-1, in both conserved blocks and variable block unique sequences, and the distribution was not uniform. Heterozygosity of PvMsp-1 alleles was higher in Asia (0.953 +/- 0.009) than in Brazil (0.813 +/- 0.047). No identical alleles were shared between Asia and Brazil, whereas all but one variable block nonrepeat sequence found in Brazil occurred in Asia. These observations suggest that A vivax populations in Asia are ancestral to Brazilian populations, and that PvMsp-1 has heterogeneity in frequency of allelic recombination events. Recurrent origins of new PvMsp-1 alleles by repeated recombination events were supported by a rapid decline in linkage disequilibrium between pairs of synonymous sites with increasing nucleotide distance, with little linkage disequilibrium at a distance of over 3 kb in a A vivax population from Thailand, evidence for an effectively high recombination rate of the parasite. Meanwhile, highly reduced nucleotide diversity was noted in a region encoding the 19-kDa C-terminal epidermal growth factor-like domain of merozoite surface protein-1, a vaccine candidate.