A Novel Terminal-Repeat Retrotransposon in Miniature (TRIM) Is Massively Expressed inEchinococcus multilocularisStem Cells

Abstract

Taeniid cestodes (including the human parasites Echinococcus spp. and Taenia solium) have very few mobile genetic elements (MGEs) in their genome, despite lacking a canonical PIWI pathway. The MGEs of these parasites are virtually unexplored, and nothing is known about their expression and silencing. In this work, we report the discovery of a novel family of small nonautonomous long terminal repeat retrotransposons (also known as terminal-repeat retrotransposons in miniature, TRIMs) which we have named ta-TRIM (taeniid TRIM). ta-TRIMs are only the second family of TRIM elements discovered in animals, and are likely the result of convergent reductive evolution in different taxonomic groups. These elements originated at the base of the taeniid tree and have expanded during taeniid diversification, including after the divergence of closely related species such as Echinococcus multilocularis and Echinococcus granulosus. They are massively expressed in larval stages, from a small proportion of full-length copies and from isolated terminal repeats that show transcriptional read-through into downstream regions, generating novel noncoding RNAs and transcriptional fusions to coding genes. In E. multilocularis, ta-TRIMs are specifically expressed in the germinative cells (the somatic stem cells) during asexual reproduction of metacestode larvae. This would provide a developmental mechanism for insertion of ta-TRIMs into cells that will eventually generate the adult germ line. Future studies of active and inactive ta-TRIM elements could give the first clues on MGE silencing mechanisms in cestodes.

The Echinococcus canadensis (G7) genome: a key knowledge of parasitic platyhelminth human diseases

“…Also, E.canG7_Brep sequences seem to be specific for flatworms since positive hits were found in Hymenolepis microstoma , Taenia solium , Schistosoma mansoni and Schistosoma japonicum , and no sequence similarity was observed in any other organisms. The E.canG7_Brep sequence had 88.5% of identity and 70.2% of coverage in relation to terminal-repeat retrotransposon in miniature (TRIM) sequences of E. granulosus (G1) (pathogen_EgG_scaffold_0006_Trim-1250290-1250818) found by Koziol [ 37 ]. The second most frequent repetitive element was E.canG7_rep142 (254 loci) which had a high copy number in all of the flatworm species sequenced so far, being variable in all of the Echinococcus species (90–91.3% of identity), and included an open reading frame (ORF) encoding for pol polyprotein.…”

“…Furthermore, E.canG7_rep142, E.canG7_rep39 and E.canG7_rep1032 contained sequences encoding for replicase domain, reverse transcriptase domain and RNA recognition domain, respectively. Recently, a novel TRIM has been found in E. multilocularis [ 37 ] but lacked evidence of active retrotransposition in E. canadensis (G7) and E. granulosus (G1). In addition, most of the E.canG7_rep (73%, 156/213) detected in E. canadensis (G7) had expression evidence (RNA-seq reads) in the protoscolex and metacestode stages.…”

Region-specific regulation of stem cell-driven regeneration in tapeworms

“…Like planarians, H. diminuta maintains a population of neoblast-like adult somatic stem cells (Roberts, 1980) that are likely responsible for their growth and regenerative ability. Recently, stem cells of multiple species of parasitic flatworms have been described (Collins et al, 2013; Koziol et al, 2014; Koziol et al, 2015; Wang et al, 2013; Koziol et al, 2010). Stem cells play crucial roles in parasite development, transmission, homeostasis, and even disease.…”

RNA interference dynamics in juvenile Fasciola hepatica are altered during in vitro growth and development

“…Our results strengthen the idea that the piwi-clade AGOs have been lost in the parasitic flatworms, only to be replaced by a parasitic flatworm specific clade ( Skinner et al, 2014 ), with an as yet unknown function. It is possible that this novel pathway acts on parasitic flatworm transposons ( DeMarco et al, 2004 ; Jacinto et al, 2011 ; Koziol et al, 2015 ), as the piRNA, endo si-RNAs and clade I AGOs do in germ line and somatic cells in other eukaryotes ( Vagin et al, 2006 ; Houwing et al, 2007 ; Chung et al, 2008 ; Ghildiyal et al, 2008 ; Kawamura et al, 2008 ). Given the difference in the number of repeat sequences between the UK and Oregon F. hepatica genomes (30.6% and 55.3%) ( McNulty et al, 2017 ) it may be that the regulation of transposable elements does not occur in the parasitic flatworms, hence the absence of PIWI AGOs in F. hepatica .…”