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疟原虫(疟原虫属)的环子孢子蛋白基因:免疫原性区域正选择的证据。

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

作者信息

Hughes A L

机构信息

Center for Demographic and Population Genetics, University of Texas Health Science Center, Houston 77225.

出版信息

Genetics. 1991 Feb;127(2):345-53. doi: 10.1093/genetics/127.2.345.

DOI:10.1093/genetics/127.2.345
PMID:1706291
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1204362/
Abstract

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.

摘要

环子孢子(CS)蛋白是疟原虫(疟原虫属)生命周期中感染脊椎动物宿主的子孢子阶段的一种细胞表面蛋白。DNA序列分析支持这样一种假说:在恶性疟原虫中,正向达尔文选择有利于CS蛋白的T细胞表位(由宿主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,非同义核苷酸替换率显著高于同义替换率,而其他基因区域并非如此。此外,这些区域中的非同义核苷酸替换导致氨基酸残基电荷变化的频率明显高于偶然预期。相比之下,在食蟹猴疟原虫中,相同区域没有正向选择的证据,并且残基电荷是保守的。CS蛋白有一个中央重复区域,它是宿主抗体的靶标。在恶性疟原虫中,重复区域的氨基酸序列在等位基因内和等位基因间都是保守的。另一方面,在食蟹猴疟原虫中,有证据表明正向选择有利于给定等位基因内两种不同重复类型的进化。

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