Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of Theileria-induced leukocyte transformation.
Comparative genome analysis of three eukaryotic parasites with differing abilities to transform leukocytes reveals key mediators of Theileria-induced leukocyte transformation.
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作者：
Hayashida K;Hara Y;Abe T;Yamasaki C;Toyoda A;Kosuge T;Suzuki Y;Sato Y;Kawashima S;Katayama T;Wakaguri H;Inoue N;Homma K;Tada-Umezaki M;Yagi Y;Fujii Y;Habara T;Kanehisa M;Watanabe H;Ito K;Gojobori T;Sugawara H;Imanishi T;Weir W;Gardner M;Pain A;Shiels B;Hattori M;Nene V;Sugimoto C
我们测定了东方泰勒虫（Theileria orientalis）的基因组序列，东方泰勒虫是一种蜱传的牛顶复门原虫寄生虫。本研究的重点是比较基因组分析东方泰勒虫相对于其他高致病性泰勒虫物种，小泰勒虫和环形泰勒虫。小锥虫和环状锥虫诱导淋巴细胞或巨噬细胞/单核细胞谱系的感染细胞的转化;相反，东方锥虫不诱导感染的白细胞的不受控制的增殖，并且主要在感染的红细胞内增殖。虽然发现三种泰勒虫物种的同源染色体之间的同线性总体上很保守，但发现亚端粒结构有很大差异，因为东方泰勒虫缺乏大的串联排列的亚端粒编码的可变分泌蛋白编码基因家族。此外，在两种转化泰勒虫属物种的基因组中发现了通过基因重复的特定基因家族的扩展，最值得注意的是TashAT/TpHN和Tar/Tpr基因家族。还鉴定了仅存在于小锥虫和环状锥虫中而不存在于东方锥虫、牛巴氏疟原虫或疟原虫中的基因家族。具有不同转化和永生化牛白细胞能力的泰勒虫属物种的基因组序列之间的差异的鉴定将提供对已经进化以诱导和调节该过程的蛋白质和机制的深入了解。T. orientalis基因组数据库可在.恶性泰勒虫感染的白细胞的癌样生长是一种独特的细胞事件，因为它涉及一种真核细胞被另一种真核细胞转化和永生化。在这项研究中，我们测序了一个非转化泰勒虫物种，东方泰勒虫的全基因组，并将其与两个恶性转化物种，小泰勒虫和环形泰勒虫的已发表序列进行了比较。这些寄生虫物种的全基因组比较突出了显著的遗传多样性，其可能与细胞内真核寄生虫转化其宿主细胞的机制的进化相关。
We sequenced the genome of Theileria orientalis, a tick-borne apicomplexan protozoan parasite of cattle. The focus of this study was a comparative genome analysis of T. orientalis relative to other highly pathogenic Theileria species, T. parva and T. annulata. T. parva and T. annulata induce transformation of infected cells of lymphocyte or macrophage/monocyte lineages; in contrast, T. orientalis does not induce uncontrolled proliferation of infected leukocytes and multiplies predominantly within infected erythrocytes. While synteny across homologous chromosomes of the three Theileria species was found to be well conserved overall, subtelomeric structures were found to differ substantially, as T. orientalis lacks the large tandemly arrayed subtelomere-encoded variable secreted protein-encoding gene family. Moreover, expansion of particular gene families by gene duplication was found in the genomes of the two transforming Theileria species, most notably, the TashAT/TpHN and Tar/Tpr gene families. Gene families that are present only in T. parva and T. annulata and not in T. orientalis, Babesia bovis, or Plasmodium were also identified. Identification of differences between the genome sequences of Theileria species with different abilities to transform and immortalize bovine leukocytes will provide insight into proteins and mechanisms that have evolved to induce and regulate this process. The T. orientalis genome database is available at . Cancer-like growth of leukocytes infected with malignant Theileria parasites is a unique cellular event, as it involves the transformation and immortalization of one eukaryotic cell by another. In this study, we sequenced the whole genome of a nontransforming Theileria species, Theileria orientalis, and compared it to the published sequences representative of two malignant, transforming species, T. parva and T. annulata. The genome-wide comparison of these parasite species highlights significant genetic diversity that may be associated with evolution of the mechanism(s) deployed by an intracellular eukaryotic parasite to transform its host cell.