Division of Veterinary Infection and Immunity, University of Glasgow, Faculty of Veterinary Medicine, Institute of Comparative Medicine, Bearsden Road, Glasgow, Scotland, G61 1QH, UK.
BMC Genomics. 2010 Jan 18;11:42. doi: 10.1186/1471-2164-11-42.
Little is known about how apicomplexan parasites have evolved to infect different host species and cell types. Theileria annulata and Theileria parva invade and transform bovine leukocytes but each species favours a different host cell lineage. Parasite-encoded proteins secreted from the intracellular macroschizont stage within the leukocyte represent a critical interface between host and pathogen systems. Genome sequencing has revealed that several Theileria-specific gene families encoding secreted proteins are positively selected at the inter-species level, indicating diversification between the species. We extend this analysis to the intra-species level, focusing on allelic diversity of two major secretome families. These families represent a well-characterised group of genes implicated in control of the host cell phenotype and a gene family of unknown function. To gain further insight into their evolution and function, this study investigates whether representative genes of these two families are diversifying or constrained within the T. annulata population.
Strong evidence is provided that the sub-telomerically encoded SVSP family and the host-nucleus targeted TashAT family have evolved under contrasting pressures within natural T. annulata populations. SVSP genes were found to possess atypical codon usage and be evolving neutrally, with high levels of nucleotide substitutions and multiple indels. No evidence of geographical sub-structuring of allelic sequences was found. In contrast, TashAT family genes, implicated in control of host cell gene expression, are strongly conserved at the protein level and geographically sub-structured allelic sequences were identified among Tunisian and Turkish isolates. Although different copy numbers of DNA binding motifs were identified in alleles of TashAT proteins, motif periodicity was strongly maintained, implying conserved functional activity of these sites.
This analysis provides evidence that two distinct secretome genes families have evolved under contrasting selective pressures. The data supports current hypotheses regarding the biological role of TashAT family proteins in the management of host cell phenotype that may have evolved to allow adaptation of T. annulata to a specific host cell lineage. We provide new evidence of extensive allelic diversity in representative members of the enigmatic SVSP gene family, which supports a putative role for the encoded products in subversion of the host immune response.
关于顶复门寄生虫如何进化以感染不同的宿主物种和细胞类型，我们知之甚少。环形泰勒虫和小泰勒虫感染并转化牛白细胞，但每种寄生虫都偏爱不同的宿主细胞谱系。从白细胞内的巨滋养体阶段分泌的寄生虫编码蛋白代表了宿主和病原体系统之间的关键界面。基因组测序表明，在种间水平上，几个顶复门特异性基因家族编码的分泌蛋白受到正选择，表明物种间的多样化。我们将这一分析扩展到种内水平，重点研究两个主要分泌家族的等位基因多样性。这些家族代表了一组特征明确的基因，这些基因与控制宿主细胞表型有关，还有一个功能未知的基因家族。为了更深入地了解它们的进化和功能，本研究调查了这两个家族的代表性基因是否在环形泰勒虫群体中多样化或受到限制。
强有力的证据表明，亚端粒编码的 SVSP 家族和靶向宿主核的 TashAT 家族在天然环形泰勒虫群体中受到了不同的压力。SVSP 基因的密码子使用不典型，呈中性进化，核苷酸替换率高，有多个插入缺失。未发现等位序列的地理亚结构。相比之下，TashAT 家族基因与控制宿主细胞基因表达有关，在蛋白质水平上高度保守，在突尼斯和土耳其分离株中鉴定到了地理亚结构的等位序列。尽管在 TashAT 蛋白的等位基因中发现了不同数量的 DNA 结合基序，但基序的周期性得到了很好的维持，这意味着这些位点的功能活性是保守的。
本分析提供了证据，表明两个不同的分泌蛋白家族在不同的选择压力下进化。这些数据支持了目前关于 TashAT 家族蛋白在管理宿主细胞表型方面的生物学作用的假说，这些假说可能已经进化，以允许环形泰勒虫适应特定的宿主细胞谱系。我们提供了关于神秘的 SVSP 基因家族代表成员的广泛等位基因多样性的新证据，这支持了编码产物在宿主免疫反应抑制中的潜在作用。
