The genome of the hydatid tapeworm Echinococcus granulosus

Abstract

A r t i c l e sThe dog tapeworm E. granulosus is one of a group of medically important parasitic helminths of the family Taeniidae (Platyhelminthes; Cestoda; Cyclophyllidea) that infect at least 50 million people globally 1 . Its life cycle involves two mammals, including an intermediate host, usually a domestic or wild ungulate (humans are accidental intermediate hosts) and a canine-definitive host, such as the domestic dog. The larval (metacestode) stage causes hydatidosis (cystic hydatid disease; cystic echinococcosis), a chronic cyst-forming disease in the intermediate (human) host. Currently, up to 3 million people are infected with E. granulosus 2,3 , and, in some areas, 10% of the population has detectable hydatid cysts by abdominal ultrasound and chest X-ray 4,5 .E. granulosus has no gut, circulatory or respiratory organs. It is monoecious, producing diploid eggs that give rise to ovoid embryos, the oncospheres. Strobilization is a notable feature of cestode biology, whereby proglottids bud distally from the anterior scolex, resulting in the production of tandem reproductive units exhibiting increasing degrees of development. A unique characteristic of the larvae (protoscoleces, PSCs) within the hydatid cyst is an ability to develop bidirectionally into an adult worm in the dog gastrointestinal tract or into a secondary hydatid cyst in the intermediate (human) host, a process triggered by bile acids 6 . Another distinct feature of E. granulosus is its capacity to infect and adapt to a large number of mammalian species as intermediate hosts, which has contributed to its cosmopolitan global distribution.Here we report the sequence and analysis of the E. granulosus genome. Comprising nine pairs of chromosomes 7 , it is one of the first cestode genomes to be sequenced and complements the recent publication by Tsai et al. 8 of a high-quality genome for Echinococcus multilocularis (the cause of alveolar echinococcosis), together with draft genomes of three other tapeworm species including E. granulosus. Our study provides insights into the biology, development, differentiation, evolution and host interaction of E. granulosus and has identified a range of drug and vaccine targets that can facilitate the development of new intervention tools for hydatid treatment and control. Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCa v b 1 may be associated with praziquantel sens...

Transposons, Genome Size, and Evolutionary Insights in Animals

“…Despite many species of annelids, nematodes, and flatworms being parasites and generally having small genome sizes [Sundberg and Pulkkinen, 2015], no difference in the percentage of transposons between free-living and parasitic species was noticed [Zheng et al, 2013].…”

Recent advances in Echinococcus genomics and stem cell research

“…Although Tsai et al (2013) reported nuclear genome sizes of ∼115 Mbp for both E. multilocularis and E. granulosus, the analysis of Zheng et al (2013) revealed ∼150 Mbp for E. granulosus which was, however, mostly due to differences in the assembly process that identified a higher proportion of repeats in the Chinese isolate when compared to the assembly of the Uruguayan isolate . In any case, and also including data from the H. microstoma and T. solium sequencing projects, the studied tapeworms have much smaller genomes than the related flukes (about three times) or free-living flatworms (about nine times), which is mostly due to smaller intergenic regions, smaller introns, and a lower content of repeats and mobile genetic elements in tapeworm genomes (Tsai et al, 2013).…”

“…Later, these cestode whole genome sequencing projects were complemented by efforts of a Chinese/Australian consortium, which produced a second E. granulosus draft sequence from a single hydatid cyst (G1 strain) using 454 and Solexa NGS . In all three Echinococcus genome projects, gene finding and annotation was supported by extensive EST-and NGS-transcriptomic analyses (RNAseq) of several life cycle stages such as oncosphere, metacestode, protoscolex and adult worms (Fernandez et al, 2002;Parkinson et al, 2012;Tsai et al, 2013;Zheng et al, 2013).…”

“…In addition to a closer understanding of parasite biology, the host-parasite relationship and parasite evolution, the quest for novel chemotherapeutic targets was surely a major rationale for the initiation of whole genome sequencing projects for E. multilocularis and E. granulosus, about 10 years ago, which culminated in the release of two highly recognised publications in 2013 (Tsai et al, 2013;Zheng et al, 2013). In the following we will briefly outline the characteristics of Echinococcus genomes and how this information, when combined with transcriptomics, can be used for the identification of novel drug targets.…”

Phylogenetic Pattern, Evolutionary Processes and Species Delimitation in the Genus Echinococcus

“…Siles-Lucas et al (2001), for example, found differences in the expression profile of the 14-3-3 gene, involved in abnormal cell proliferation, between E. granulosus and E. multilocularis, and suggested that this may partially explain differences in metacestode growth behavior. The recent publication of whole genome sequences for E. granulosus and E. multilocularis (Tsai et al, 2013;Zheng et al, 2013) enhances the potential of this approach. As yet, only limited interpretations have been made from the genomic data, but even these open up new avenues for research.…”