Circumsporozoite protein genes of malaria parasites (Plasmodium spp.): evidence for positive selection on immunogenic regions.

Circumsporozoite protein genes of malaria parasites (Plasmodium spp.): evidence for positive selection on immunogenic regions.
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疟疾寄生虫(疟原虫属)的环子孢子蛋白基因:免疫原性区域正向选择的证据。

DOI:
10.1093/genetics/127.2.345
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发表时间:
1991
期刊:
影响因子:
3.3
通讯作者:
Hughes,AL
Hughes,AL
中科院分区:
生物学2区
文献类型:
--
作者:
Hughes,AL

文献摘要

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相似文献

环孢子虫(CS)蛋白是孢子虫的细胞表面蛋白,孢子虫是感染脊椎动物宿主的疟疾寄生虫(疟原虫)生命周期的一个阶段。DNA序列分析支持恶性疟原虫的假设,即阳性达尔文选择有利于CS蛋白的T细胞表位(宿主MHC分子呈递给T细胞的肽)的多样性。在编码恶性疟原虫T细胞表位的基因区域,非同义核苷酸取代率显著高于同义核苷酸取代率,而在其他基因区域则不然。此外,这些区域的非同义核苷酸取代引起氨基酸残基电荷变化的频率明显高于偶然预期。相比之下,在食胞疟原虫中,相同的区域没有显示出正选择的证据,残基电荷是保守的。CS蛋白有一个中心重复区,是宿主抗体的靶点。在恶性疟原虫中,重复区域的氨基酸序列在等位基因内部和之间是保守的。另一方面,在P. cynomolgi中,有证据表明,正选择倾向于在给定的等位基因中进化出两种不同的重复类型。
The circumsporozoite (CS) protein is a cell surface protein of the sporozoite, the stage of the life cycle of malaria parasites (Plasmodium spp.) that infects the vertebrate host. Analysis of DNA sequences supports the hypothesis that in Plasmodium falciparum, positive Darwinian selection favors diversity in the T-cell epitopes (peptides presented to T cells by host MHC molecules) of the CS protein. In gene regions encoding T cell epitopes of P. falciparum, the rate of nonsynonymous nucleotide substitution is significantly higher than that of synonymous substitution, whereas this is not true of other gene regions. Furthermore nonsynonymous nucleotide substitutions in these regions cause a change of amino acid residue charge significantly more frequently than expected by chance. By contrast, in Plasmodium cynomolgi, the same regions show no evidence of positive selection, and residue charge is conserved. The CS protein has a central repeat region, which is the target of host antibodies. In P. falciparum, the amino acid sequence of the repeat region is conserved within and between alleles. In P. cynomolgi, on the other hand, there is evidence that positive selection has favored evolution of two different repeat types within a given allele.