Genomic resources and genetic studies of parasitic flukes, with an emphasis on Clonorchis sinensis
Document TypePhD thesis
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© 2019 Dr. Daxi Wang
Clonorchiasis is a complex hepatobiliary disease caused by the foodborne parasite, Clonorchis sinensis (family Opisthorchiidae). This disease can induce cholangiocarcinoma (CCA), a malignant cancer of the bile ducts, and has a major socioeconomic impact on ~ 35 million people predominantly in East Asia. Currently, no vaccine is available to prevent clonorchiasis, and repeated use of the only recommended drug, praziquantel (PZQ) increases the risk of developing drug resistance. Further understanding of the disease epidemiology relies on the knowledge of genetic variation of C. sinensis in endemic areas. Moreover, evidence of karyotypic variation within C. sinensis highlights the importance of comparing the genomes of geographically distinct isolates of this parasite. The two predominant research aims of this thesis were to decode the mitochondrial (mt) and nuclear genomes of a Korean isolate of C. sinensis and assess genetic variation, using high-throughput sequencing technologies and advanced bioinformatic workflows. The mt and nuclear genomes for a C. sinensis isolate from Korea (Cs-k2) were sequenced, assembled, characterised and compared with one or more isolates. In addition, a refined bioinformatic workflow was designed to infer high quality syntenic blocks between the nuclear genome and a previously published draft genome of another isolate from China. The results not only reveal a high level of nucleotide similarity within the syntenic regions, but also pinpoint variable genes that might be central to infection and/or adaptive process. The mt and nuclear genomes and the syntenic blocks now serve as a solid foundation for a future genetic analysis of C. sinensis. The mt genome, on one hand, confirmed the specific identity of the specimen, on the other hand, highlighted potential challenges with using mtDNA markers for genetic analyses. In contrast to the mt genome, the syntenic blocks of the nuclear genome exhibit major potential for future genetic studies due to a vast extent of nucleotide differences in coding regions. These blocks also contain a substantial number of genetic loci that might enhance knowledge of host- parasite relationships in an evolutionary context. Compared with coding regions, the genetic variation in the intronic regions showed an improved phylogenetic signal at both the whole genome and individual gene levels. In future, improved quality of the assembly and annotation of nuclear genomes should be achieved using long read data, allowing a broader range of genetic and structural variation to be identified using whole genomic data of representative individuals. Furthermore, a systematic bioinformatic framework is required to discover individual variants, infer population structure and identify adaptive selection, with the consideration of parasitic life cycle and demographic history. Although the present thesis focused predominantly on C. sinensis, the work extended logically to another trematode. A third research aim was addressed to explore the population genetic structure of a related trematode parasite, Schistosoma japonicum in China and to identify genes under positive selection in particular geographical locations. Clearly, the findings of this thesis and the approaches established should have important and broad implications for studies of a range of flatworm parasites.
KeywordsClonorchis sinensis; phylogeny; Schistosoma japonicum; genome; genetic variation; trematode
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