The draft genome of the carcinogenic human liver fluke Clonorchis sinensis

Abstract

BackgroundClonorchis sinensis is a carcinogenic human liver fluke that is widespread in Asian countries. Increasing infection rates of this neglected tropical disease are leading to negative economic and public health consequences in affected regions. Experimental and epidemiological studies have shown a strong association between the incidence of cholangiocarcinoma and the infection rate of C. sinensis. To aid research into this organism, we have sequenced its genome.ResultsWe combined de novo sequencing with computational techniques to provide new information about the biology of this liver fluke. The assembled genome has a total size of 516 Mb with a scaffold N50 length of 42 kb. Approximately 16,000 reliable protein-coding gene models were predicted. Genes for the complete pathways for glycolysis, the Krebs cycle and fatty acid metabolism were found, but key genes involved in fatty acid biosynthesis are missing from the genome, reflecting the parasitic lifestyle of a liver fluke that receives lipids from the bile of its host. We also identified pathogenic molecules that may contribute to liver fluke-induced hepatobiliary diseases. Large proteins such as multifunctional secreted proteases and tegumental proteins were identified as potential targets for the development of drugs and vaccines.ConclusionsThis study provides valuable genomic information about the human liver fluke C. sinensis and adds to our knowledge on the biology of the parasite. The draft genome will serve as a platform to develop new strategies for parasite control.

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

“…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.…”

Increased taxon sampling reveals thousands of hidden orthologs in flatworms

“…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.…”

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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].…”

“…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.…”