Abstract

Fasciola gigantica and Fasciola hepatica are causative pathogens of fascioliasis, with the widest latitudinal, longitudinal, and altitudinal distribution; however, among parasites, they have the largest sequenced genomes, hindering genomic research. In the present study, we used various sequencing and assembly technologies to generate a new high-quality Fasciola gigantica reference genome. We improved the integration of gene structure prediction, and identified two independent transposable element expansion events contributing to (1) the speciation between Fasciola and Fasciolopsis during the Cretaceous-Paleogene boundary mass extinction, and (2) the habitat switch to the liver during the Paleocene-Eocene Thermal Maximum, accompanied by gene length increment. Long interspersed element (LINE) duplication contributed to the second transposon-mediated alteration, showing an obvious trend of insertion into gene regions, regardless of strong purifying effect. Gene ontology analysis of genes with long LINE insertions identified membrane-associated and vesicle secretion process proteins, further implicating the functional alteration of the gene network. We identified 852 predicted excretory/secretory proteins and 3300 protein-protein interactions between Fasciola gigantica and its host. Among them, copper/zinc superoxide dismutase genes, with specific gene copy number variations, might play a central role in the phase I detoxification process. Analysis of 559 single-copy orthologs suggested that Fasciola gigantica and Fasciola hepatica diverged at 11.8 Ma near the Middle and Late Miocene Epoch boundary. We identified 98 rapidly evolving gene families, including actin and aquaporin, which might explain the large body size and the parasitic adaptive character resulting in these liver flukes becoming epidemic in tropical and subtropical regions.

Highlights

  • Fasciola gigantica and Fasciola hepatica, known as liver flukes, are two species in the genus Fasciola, which cause fascioliasis commonly in domestic and wild ruminants, and are causal agents of fascioliasis in humans

  • Fascioliasis is a neglected zoonotic tropical disease of humans, which reduces the productivity of animal industries, and imposes an economic burden of at least 3.2 billion dollars annually

  • There are four assemblies for F. hepatica and two assemblies for F. gigantica at National Center for Biotechnology Information (NCBI), the inherent limited ability of short reads based assemblies made the completeness of genome sequences and the quality of gene annotation challenging

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Summary

Introduction

Fasciola gigantica and Fasciola hepatica, known as liver flukes, are two species in the genus Fasciola, which cause fascioliasis commonly in domestic and wild ruminants, and are causal agents of fascioliasis in humans. Four assemblies for F. hepatica and two assemblies for F. gigantica have been deposited at the NCBI [4,5,6,7] These assemblies reveal a large genome with a high percentage of repeat regions in Fasciola species, and provided valuable insights into features of adaptation and evolution. These assemblies are based on the short read Illumina sequencing or hybrid sequencing methods, with limited ability to span large families of repeats. Subsequent gene annotation analysis using current assemblies were challenging, with abundant transposition events occurring over evolutionary history, which significantly increased the repeat components in intron regions, resulting in considerable fragmentation in gene annotation

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