The draft genome of the carcinogenic human liver fluke Clonorchis sinensis

Wang, Xiaoyun; Chen, Wenjun; Huang, Yan; Sun, Jiufeng; Men, Jingtao; Liu, Hailiang; Luo, Fang; Guo, Lei; Lv, Xiaoli; Deng, Chang-Yan; Zhou, Chenhui; Fan, Yali; Li, Xuerong; Huang, Lisi; Hu, Yue; Liang, Chi; Hu, Xuchu; Xu, Jin; Yu, Xinbing

doi:10.1186/gb-2011-12-10-r107

Cited by 166 publications

(148 citation statements)

References 87 publications

(122 reference statements)

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“…The availability of entire genome sequences of related species of liver flukes, such as C. sinensis (89) and blood flukes (38 -40), now provides unprecedented opportunities to (i) conduct comparative proteomic comparisons; (ii) elucidate the structures and functions of key molecules (e.g. "endogenous" and "exogenous" cathepsins); (iii) explore novel biological pathways (e.g.…”

Section: Discussionmentioning

confidence: 99%

A Deep Exploration of the Transcriptome and “Excretory/Secretory” Proteome of Adult Fascioloides magna

Cantacessi

Mulvenna

Young

et al. 2012

Molecular & Cellular Proteomics

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Parasitic liver flukes of the family Fasciolidae are responsible for major socioeconomic losses worldwide. However, at present, knowledge of the fundamental molecular biology of these organisms is scant. Here, we characterize, for the first time, the transcriptome and secreted proteome of the adult stage of the "giant liver fluke," Fascioloides magna, using Illumina sequencing technology and one-dimensional SDS-PAGE and OFFGEL protein electrophoresis, respectively. A total of ϳ54,000,000 reads were generated and assembled into ϳ39,000 contiguous sequences (contigs); ϳ20,000 peptides were predicted and classified based on homology searches, protein motifs, gene ontology, and biological pathway mapping. From the predicted proteome, 48.1% of proteins could be assigned to 384 biological pathway terms, including "spliceosome," "RNA transport," and "endocytosis." Putative proteins involved in amino acid degradation were most abundant. Of the 835 secreted proteins predicted from the transcriptome of F. magna, 80 were identified in the excretory/secretory products from this parasite. Highly represented were antioxidant proteins, followed by peptidases (particularly cathepsins) and proteins involved in carbohydrate metabolism. The integration of transcriptomic and proteomic datasets generated herein sets the scene for future studies aimed at exploring the potential role(s) that molecules might play at the hostparasite interface and for establishing novel strategies for the treatment or control of parasitic fluke infections. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

A Deep Exploration of the Transcriptome and “Excretory/Secretory” Proteome of Adult Fascioloides magna

Cantacessi

Mulvenna

Young

et al. 2012

Molecular & Cellular Proteomics

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“…The recovered hidden orthologs have an immediate impact on our understanding of gene complement evolution in Platyhelminthes, particularly those lineages that are the subject of intense research, such as the regenerative model Schmidtea mediterranea and parasitic flatworms (Berriman et al 2009;Wang et al 2011;Olson et al 2012;. The identification of fast-evolving orthologs for important centrosomal proteins in S. mediterranea and other flatworms lineages (Fig.…”

Section: Wwwgenomeorgmentioning

confidence: 99%

“…The use of more molecularly conserved flatworm lineages, such as P. vittatus, can improve the identification of candidate genes, as well as help with the annotation of the increasingly abundant flatworm RNA-seq and genomic data sets (Berriman et al 2009;Wang et al 2011;Tsai et al 2013;Robb et al 2015;Wasik et al 2015;Brandl et al 2016). Therefore, we have now made available an assembled version of those highly complete nonplanarian flatworm transcriptomes in PlanMine, an integrated web resource of transcriptomic data for planarian researchers (Brandl et al 2016).…”

Section: Uncovered Hidden Orthology In Flatwormsmentioning

confidence: 99%

Increased taxon sampling reveals thousands of hidden orthologs in flatworms

et al. 2017

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Gains and losses shape the gene complement of animal lineages and are a fundamental aspect of genomic evolution. Acquiring a comprehensive view of the evolution of gene repertoires is limited by the intrinsic limitations of common sequence similarity searches and available databases. Thus, a subset of the gene complement of an organism consists of hidden orthologs, i.e., those with no apparent homology to sequenced animal lineages-mistakenly considered new genes-but actually representing rapidly evolving orthologs or undetected paralogs. Here, we describe Leapfrog, a simple automated BLAST pipeline that leverages increased taxon sampling to overcome long evolutionary distances and identify putative hidden orthologs in large transcriptomic databases by transitive homology. As a case study, we used 35 transcriptomes of 29 flatworm lineages to recover 3427 putative hidden orthologs, some unidentified by OrthoFinder and HaMStR, two common orthogroup inference algorithms. Unexpectedly, we do not observe a correlation between the number of putative hidden orthologs in a lineage and its "average" evolutionary rate. Hidden orthologs do not show unusual sequence composition biases that might account for systematic errors in sequence similarity searches. Instead, gene duplication with divergence of one paralog and weak positive selection appear to underlie hidden orthology in Platyhelminthes. By using Leapfrog, we identify key centrosome-related genes and homeodomain classes previously reported as absent in free-living flatworms, e.g., planarians. Altogether, our findings demonstrate that hidden orthologs comprise a significant proportion of the gene repertoire in flatworms, qualifying the impact of gene losses and gains in gene complement evolution.

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“…This highlights the fact that there are physio-chemical differences in the channel for possible substrate recognition function and specificity of isoforms. This may partly explain the functional outcomes of inflammation, hepatic fibrosis and cancer caused by infection of the parasite, C. sinensis [5][6][7].…”

Section: Sequence Analysismentioning

confidence: 99%

“…Interestingly, the genome of the liver fluke revealed that there are genes missing for the production of its own fatty acids. This makes the bile as the only source of lipid for its growth [5]. The CsIIIPLA 2 is therefore an important energy source enzyme of the adult parasite.…”

Section: Introductionmentioning

confidence: 99%

Delineation of the Structural Elements of Oriental Liver Fluke PLA2 Isoforms for Potent Drug Designing

et al. 2013

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Clonorchis sinensis or the Chinese liver fluke is one of the most prevalent parasites affecting a major population in the oriental countries. The parasite lacks lipid generating mechanisms but is exposed to fatty acid rich bile in the liver. A secretory phospholipase A 2 , an enzyme that breaks down complex lipids, is important for the growth of the parasite. The enzyme is also implicated in the pathogenesis leading up to the hepatic fibrosis and its complications including cancer. The five isoforms of this particular enzyme from the parasite therefore qualify as potential drug targets. In this study, a detailed structural and ligand binding analysis of the isoforms has been done by modeling. The overall three dimensional structures of the isoforms are well conserved with three helices and a bwing stabilized by four disulfide bonds. There are characteristic differences at the calcium binding loop, hydrophobic channel and the C-terminal domain that can potentially be exploited for drug binding. But the most significant feature pertains to the catalytic site where the isoforms exhibit three variations of either a histidineaspartate-tyrosine or histidine-glutamate-tyrosine or histidine-aspartate-phenylalanine. Molecular docking studies show that isoform specific residues and their conformations in the substrate binding hydrophobic channel make unique interactions with certain inhibitor molecules resulting in a perfect tight fit. The proposed ligand molecules have a predicted affinity in micro-molar to nano-molar range. Interestingly, few of the ligand binding interaction patterns is in accordance to the phylogenetic studies to thereby establish the usefulness of evolutionary mechanisms in aiding ligand design. The molecular diversity of the parasitic PLA 2 described in this study provides a platform for personalized medicine in the therapeutics of clonorchiasis.

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The draft genome of the carcinogenic human liver fluke Clonorchis sinensis

Cited by 166 publications

References 87 publications

A Deep Exploration of the Transcriptome and “Excretory/Secretory” Proteome of Adult Fascioloides magna

A Deep Exploration of the Transcriptome and “Excretory/Secretory” Proteome of Adult Fascioloides magna

Increased taxon sampling reveals thousands of hidden orthologs in flatworms

Delineation of the Structural Elements of Oriental Liver Fluke PLA2 Isoforms for Potent Drug Designing

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