Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian Plasmodium falciparum populations.
Sequence diversity and natural selection at domain I of the apical membrane antigen 1 among Indian Plasmodium falciparum populations.
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DOI：
10.1186/1475-2875-6-154
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发表时间：
2007-11-22
期刊：
影响因子：
3
通讯作者：
Sharma YD
中科院分区：
文献类型：
--
作者：
Garg S;Alam MT;Das MK;Dev V;Kumar A;Dash AP;Sharma YD
恶性疟原虫顶端膜抗原1（AMA 1）是一种主要的疟疾疫苗候选抗原。完整的AMA 1蛋白由三个结构域组成，其中结构域I表现出高序列多态性，因此被命名为高变区（HVR）。本研究描述了印度恶性疟原虫分离株之间的ama 1基因的结构域I的遗传多态性和自然选择的程度。从印度5个不同地理区域收集的157株恶性疟原虫分离株中PCR扩增覆盖结构域I的ama 1基因部分并测序。使用DnaSP ver. 4. 10. 9和MEGA 3.0版软件包。在157个测序的菌株中，共观察到57个AMA 1单倍型。这57种单倍型中有46种是首次报道。从疟疾高传播地区（阿萨姆邦、奥里萨邦、安达曼和尼科巴群岛）收集的寄生虫与疟疾低传播地区（北方邦和果阿）相比显示出更多的单倍型（H）和核苷酸多样性π。所有5个印度恶性疟原虫亚群的比较表明，中等水平的遗传分化和有限的基因流（固定指数范围从0.048到0.13）之间的人口。非同义和同义突变率之间的差异、Tajima's D和McDonald-Kreitman检验统计表明，AMA 1抗原结构域I的多样性是由于正向自然选择。最小重组事件也很高，表明重组在产生AMA 1等位基因多样性中可能起作用。与北方邦和果阿相比，阿萨姆邦、奥里萨邦、安达曼和尼科巴群岛种群的遗传多样性和多样化选择水平更高。这些群体之间的基因流量适中。本研究结果对AMA 1为基础的疟疾疫苗的研制具有一定的参考价值。
The Plasmodium falciparum apical membrane antigen 1 (AMA1) is a leading malaria vaccine candidate antigen. The complete AMA1 protein is comprised of three domains where domain I exhibits high sequence polymorphism and is thus named as the hyper-variable region (HVR). The present study describes the extent of genetic polymorphism and natural selection at domain I of the ama1 gene among Indian P. falciparum isolates. The part of the ama1 gene covering domain I was PCR amplified and sequenced from 157 P. falciparum isolates collected from five different geographical regions of India. Statistical and phylogenetic analyses of the sequences were done using DnaSP ver. 4. 10. 9 and MEGA version 3.0 packages. A total of 57 AMA1 haplotypes were observed among 157 isolates sequenced. Forty-six of these 57 haplotypes are being reported here for the first time. The parasites collected from the high malaria transmission areas (Assam, Orissa, and Andaman and Nicobar Islands) showed more haplotypes (H) and nucleotide diversity π as compared to low malaria transmission areas (Uttar Pradesh and Goa). The comparison of all five Indian P. falciparum subpopulations indicated moderate level of genetic differentiation and limited gene flow (Fixation index ranging from 0.048 to 0.13) between populations. The difference between rates of non-synonymous and synonymous mutations, Tajima's D and McDonald-Kreitman test statistics suggested that the diversity at domain I of the AMA1 antigen is due to positive natural selection. The minimum recombination events were also high indicating the possible role of recombination in generating AMA1 allelic diversity. The level of genetic diversity and diversifying selection were higher in Assam, Orissa, and Andaman and Nicobar Islands populations as compared to Uttar Pradesh and Goa. The amounts of gene flow among these populations were moderate. The data reported here will be valuable for the development of AMA1-based malaria vaccine.
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影响因子：
1.5
作者：
Escalante, AA;Grebert, HM;Lal, AA
通讯作者：
Lal, AA
DOI：
10.1016/s0169-4758(96)10077-6
发表时间：
1997-01-01
期刊：
PARASITOLOGY TODAY
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
1.5
作者：
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通讯作者：
THOMAS, AW
DOI：
10.1098/rstb.2001.1010
发表时间：
2002-01-29
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
--
作者：
Cowman, AF;Baldi, DL;Crabb, BS
通讯作者：
Crabb, BS