Elsheikha Hany M, Mansfield Linda S
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Parasitol Res. 2004 Dec;94(6):452-9. doi: 10.1007/s00436-004-1237-y. Epub 2004 Oct 28.
The major surface antigen gene 1 (SAG1) is conserved among members of Sarcocystidae and may play an important role in parasite pathogenesis. Additionally, generation and selection of different antigenic variants of SAG1 has the potential for inclusion in a subunit vaccine or in the development of a diagnostic assay. In this study, patterns of nucleotide polymorphism were used to test the hypothesis that natural selection promotes diversity in different parts of SAG1 of Sarcocystis neurona. Nucleotide and amino acid sequence analysis of SAG1 from multiple S. neurona isolates identified two alleles. Sequences were identical intra-allele and highly divergent inter-alleles. Also, phylogenetic reconstruction showed sequences clustering into two clades. Tajima's and Fu and Li's neutrality tests indicated that selection is more likely to be acting on SAG1. Moreover, a sliding window analysis based on the ratio of silent substitutions to amino acid replacements provided strong evidence that two short segments in the central and 3' domain of SAG1 have been under positive selection in the divergence of the two alleles, suggesting that it may be important for the evasion of host immune responses and would be a suitable target for vaccine development.
主要表面抗原基因1（SAG1）在肉孢子虫科成员中保守，可能在寄生虫发病机制中起重要作用。此外，SAG1不同抗原变体的产生和选择有潜力被纳入亚单位疫苗或用于开发诊断检测方法。在本研究中，核苷酸多态性模式被用于检验自然选择促进神经肉孢子虫SAG1不同区域多样性这一假设。对多个神经肉孢子虫分离株的SAG1进行核苷酸和氨基酸序列分析，鉴定出两个等位基因。等位基因内序列相同，等位基因间高度 divergent 。此外，系统发育重建显示序列聚为两个分支。 Tajima检验以及Fu和Li中性检验表明，选择更有可能作用于SAG1。此外，基于沉默替代与氨基酸替换比率的滑动窗口分析提供了有力证据，表明SAG1中央和3'结构域中的两个短片段在两个等位基因的分歧中受到正选择，这表明它可能对逃避宿主免疫反应很重要，并且将是疫苗开发的合适靶点。
