High-quality reference genome of Fasciola gigantica: Insights into the genomic signatures of transposon-mediated evolution and specific parasitic adaption in tropical regions

Author summary 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. Although there are four assemblies for F. hepatica and two assemblies for F. gigantica at NCBI, the inherent limited ability of short reads based assemblies made the completeness of genome sequences and the quality of gene annotation challenging. Here, we report the Pacbio assembly of reference genome for F. gigantica, and the quality of assembly and gene annotation are significantly improved compared with previous assemblies. Besides, we found the evidence of transposon-mediated evolution, especially for LINE insertions into gene regions between 41 Ma and 62 Ma, contributing to the speciation and adaption of the Fasciola ancestors. Furthermore, we identified F. gigantica specific gene duplication including 98 gene families, and 3300 protein-protein interactions between F. gigantica and the host in the small intestine and liver environment. These results illustrate the genomic and gene evolution of F. gigantica potentially shaping multiple parasitic characters. 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.

Automated summary

Fascioliasis is a neglected zoonotic tropical disease that imposes a significant economic burden. The Pacbio assembly of the reference genome for F. gigantica reported in the study significantly improved assembly and gene annotation quality, and revealed evidence of transposon-mediated evolution.