Putaporntip Chaturong, Jongwutiwes Somchai, Sakihama Naoko, Ferreira Marcelo U, Kho Weon-Gyu, Kaneko Akira, Kanbara Hiroji, Hattori Tetsuya, Tanabe Kazuyuki
Laboratory of Biology and Department of Mathematics, Osaka Institute of Technology, Osaka 535-8585, Japan.
Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16348-53. doi: 10.1073/pnas.252348999. Epub 2002 Dec 4.
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 P. 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 P. 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.
间日疟原虫（PvMsp-1）是最广泛流行的人类疟原虫，对来自不同地理区域的40个分离株的完整核苷酸序列进行了评估，以研究其裂殖子表面蛋白-1基因的组织和等位基因重组情况。对31个不同等位基因的比对揭示了PvMsp-1的镶嵌组织，它由七个等位基因间保守区组成，两侧是六个可变区。可变区在重复序列和非重复独特序列方面表现出广泛的变异。在PvMsp-1的整个区域，包括保守区和可变区独特序列中，都分布着大量的重组位点，且分布并不均匀。PvMsp-1等位基因的杂合度在亚洲（0.953±0.009）高于巴西（0.813±0.047）。亚洲和巴西之间没有共享相同的等位基因，而在巴西发现的除一个可变区非重复序列外的所有序列在亚洲都有出现。这些观察结果表明，亚洲的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上具有异质性。随着核苷酸距离增加，同义位点对之间的连锁不平衡迅速下降，这支持了新的PvMsp-1等位基因通过重复重组事件的反复起源，在来自泰国的间日疟原虫种群中，超过3 kb的距离几乎没有连锁不平衡，这证明了该寄生虫具有高效的重组率。同时，在作为疫苗候选物的裂殖子表面蛋白-1的19 kDa C末端表皮生长因子样结构域编码区域，观察到核苷酸多样性大幅降低。
