Molecular changes in Opisthorchis viverrini (Southeast Asian liver fluke) during the transition from the juvenile to adult stage

The Southeast Asian liver fluke (Opisthorchis viverrini) chronically infects and affects millions of people in parts of Asia. The disease caused by this parasite (= opisthorchiasis) can lead to chronic illness and, importantly, is known to induce malignant cancer (= cholangiocarcinoma). In spite of the substantial socio-economic impact of O. viverrini, little is known, at the molecular level, about the parasite itself, its interplay with its hosts and the mechanisms underpinning disease and/or carcinogenesis. Here, we generated extensive RNA-seq data from transcript libraries representing adult and juvenile stages of O. viverrini using the Illumina GAII platform. These data were combined with previously published transcriptomic data for this species (based on 454 technology), yielding a combined assembly of significantly increased quality and allowing quantitative assessment of transcription in the juvenile and adult stage of this species. This new assembly reveals that despite the substantial biological similarities between the human liver flukes, Clonorchis sinensis and Opisthorchis viverinni, there are distinct and previously unrecognized differences in major aspects of their molecular biology, including significant differences in the asparaginyl endopeptidase-like and cathepsin L-like cysteine peptidases (which are highly transcribed in juvenile O. viverrini) which are known to play key roles in major parasitological functions including tissue migration, immuno-evasion and feeding. We also propose an alternative hypothesis for the evolution of these key molecules (which are both drug and vaccine targets) among the socioeconomically important trematodes that suggests gene loss as a major shaping force among the fluke cysteine peptidases.

东南亚肝吸虫（Opisthorchis viverrini）可在亚洲部分地区慢性感染并危害数百万民众。该寄生虫引发的疾病（后睾吸虫病，opisthorchiasis）可导致慢性病症，尤为关键的是，其被证实可诱发恶性肿瘤（胆管癌，cholangiocarcinoma）。尽管麝猫后睾吸虫具有显著的社会经济影响，但目前在分子层面，人们对该寄生虫本身、其与宿主的相互作用，以及疾病和/或致癌作用（carcinogenesis）的潜在机制仍知之甚少。本研究依托Illumina GAII测序平台，构建了涵盖麝猫后睾吸虫成虫与幼体阶段的转录组文库，并生成了大规模RNA测序数据集。研究团队将这些数据与该物种此前已发表的转录组数据（基于454测序技术）进行整合，最终获得了质量大幅提升的联合组装结果，同时实现了对该物种幼体与成虫阶段转录水平的定量评估。这一新组装结果显示，尽管华支睾吸虫（Clonorchis sinensis）与麝猫后睾吸虫在生物学特性上存在诸多相似之处，但二者在分子生物学的核心维度存在显著且此前未被认知的差异，其中包括天冬酰胺内肽酶样（asparaginyl endopeptidase-like）与组织蛋白酶L样（cathepsin L-like）半胱氨酸肽酶（cysteine peptidases）的显著差异——这类酶在麝猫后睾吸虫幼体中呈高转录水平，且已知其在组织迁移、免疫逃逸与摄食等关键寄生功能中发挥核心作用。此外，本研究还针对兼具药物与疫苗靶点属性的关键分子在具有重要社会经济影响的吸虫类（trematodes）中的演化，提出了一种新假说，该假说指出基因丢失是塑造吸虫半胱氨酸肽酶家族的主要驱动因素。