Abstract
Schistosomiasis is a neglected tropical disease that affects more than 200 million people worldwide. The main disease-causing agents, Schistosoma japonicum, S. mansoni and S. haematobium, are blood flukes that have complex life cycles involving a snail intermediate host. In Asia, S. japonicum causes hepatointestinal disease (schistosomiasis japonica) and is challenging to control due to a broad distribution of its snail hosts and range of animal reservoir hosts. In China, extensive efforts have been underway to control this parasite, but genetic variability in S. japonicum populations could represent an obstacle to eliminating schistosomiasis japonica. Although a draft genome sequence is available for S. japonicum, there has been no previous study of molecular variation in this parasite on a genome-wide scale. In this study, we conducted the first deep genomic exploration of seven S. japonicum populations from mainland China, constructed phylogenies using mitochondrial and nuclear genomic data sets, and established considerable variation between some of the populations in genes inferred to be linked to key cellular processes and/or pathogen-host interactions. Based on the findings from this study, we propose that verifying intraspecific conservation in vaccine or drug target candidates is an important first step toward developing effective vaccines and chemotherapies against schistosomiasis.
Highlights
The reliance on praziquantel alone to treat/control schistosomiasis over a long period of time carries a risk of the emergence of drug resistance[10,11]
Phylogenetic trees constructed using Bayesian inference (BI; nucleotide and amino acid) and maximum parsimony (MP; nucleotide only) methods revealed two well-supported clades (Supplementary Fig. 2): one including populations Sj6 (Tianquan, Sichuan) and Sj7 (Dali, Yunnan) from provinces in Western China, and the second with Sj1 (Jiashan, Zhejiang), Sj4 (Wuhan, Hubei) and Sj5 (Yueyang, Hunan) from provinces in Eastern China. These results, were inconsistent with those obtained by maximum likelihood (ML; nucleotide and protein) and maximum parsimony (MP; protein) analyses, using the aligned mt protein sequence data set
Through the sequencing and analyses of seven new and all publicly available mt genome sequences of S. japonicum[44], we confirmed that mitochondrial data sets lacked sufficient signal to reliably establish relationships among populations, consistent with previous findings[24,25,43,44]
Summary
The reliance on praziquantel alone to treat/control schistosomiasis over a long period of time carries a risk of the emergence of drug resistance[10,11]. Microsatellite, mitochondrial (mt) and enzymatic markers were used to reveal genetic variation among isolates of S. japonicum from various regions in China and surrounding, coastal islands[21,22,23,24,25,26], or to identify genetic bottlenecks in laboratory strains of this parasite[27] These observational studies have been informative, none of them tightly linked genotype to biological traits of the parasite, such as infectivity, pathogenicity and/or immunogenicity. The advent of high throughput sequencing technologies[28,29] and the availability of a draft genome for S. japonicum[13] have paved the way toward genome-wide studies of natural and laboratory-adapted populations of S. japonicum from humans and reservoir hosts To this end, we undertook here the first deep genomic exploration of various S. japonicum populations from China to reveal their systematic relationships as well as considerable genetic variation between some populations, with an impact on numerous genes associated with key metabolic and signalling pathways, cellular processes and/or pathogen-host interactions
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