Philippsen Gisele S, Wilson R Alan, DeMarco Ricardo
Departamento de Física e Ciência Interdisciplinar, Instituto de Física de São Carlos, Universidade de São Paulo, São Carlos, São Paulo, Brazil.
Centre for Immunology and Infection, Department of Biology, University of York, United Kingdom.
Genome Biol Evol. 2015 Jan 6;7(2):431-43. doi: 10.1093/gbe/evu287.
Study of proteins located at the host-parasite interface in schistosomes might provide clues about the mechanisms utilized by the parasite to escape the host immune system attack. Micro-exon gene (MEG) protein products and venom allergen-like (VAL) proteins have been shown to be present in schistosome secretions or associated with glands, which led to the hypothesis that they are important components in the molecular interaction of the parasite with the host. Phylogenetic and structural analysis of genes and their transcripts in these two classes shows that recent species-specific expansion of gene number for these families occurred separately in three different species of schistosomes. Enrichment of transposable elements in MEG and VAL genes in Schistosoma mansoni provides a credible mechanism for preferential expansion of gene numbers for these families. Analysis of the ratio between synonymous and nonsynonymous substitution rates (dN/dS) in the comparison between schistosome orthologs for the two classes of genes reveals significantly higher values when compared with a set of a control genes coding for secreted proteins, and for proteins previously localized in the tegument. Additional analyses of paralog genes indicate that exposure of the protein to the definitive host immune system is a determining factor leading to the higher than usual dN/dS values in those genes. The observation that two genes encoding S. mansoni vaccine candidate proteins, known to be exposed at the parasite surface, also display similar evolutionary dynamics suggests a broad response of the parasite to evolutionary pressure imposed by the definitive host immune system.
对血吸虫宿主 - 寄生虫界面处蛋白质的研究可能会为寄生虫逃避宿主免疫系统攻击所利用的机制提供线索。已证明微小外显子基因（MEG）蛋白产物和类毒液过敏原（VAL）蛋白存在于血吸虫分泌物中或与腺体相关，这导致了一种假设，即它们是寄生虫与宿主分子相互作用中的重要组成部分。对这两类基因及其转录本的系统发育和结构分析表明，这些家族基因数量最近的物种特异性扩增分别发生在三种不同的血吸虫物种中。曼氏血吸虫MEG和VAL基因中转座元件的富集为这些家族基因数量的优先扩增提供了可靠的机制。在两类基因的血吸虫直系同源物比较中，同义替换率与非同义替换率之比（dN/dS）的分析显示，与一组编码分泌蛋白以及先前定位于皮层的蛋白的对照基因相比，其值显著更高。对旁系同源基因的进一步分析表明，蛋白质暴露于终宿主免疫系统是导致这些基因中dN/dS值高于正常水平的一个决定性因素。观察到两个编码曼氏血吸虫疫苗候选蛋白的基因（已知在寄生虫表面暴露）也表现出类似的进化动态，这表明寄生虫对终宿主免疫系统施加的进化压力有广泛的反应。
