A Helitron transposon reconstructed from bats reveals a novel mechanism of genome shuffling in eukaryotes

Abstract

Helitron transposons capture and mobilize gene fragments in eukaryotes, but experimental evidence for their transposition is lacking in the absence of an isolated active element. Here we reconstruct Helraiser, an ancient element from the bat genome, and use this transposon as an experimental tool to unravel the mechanism of Helitron transposition. A hairpin close to the 3′-end of the transposon functions as a transposition terminator. However, the 3′-end can be bypassed by the transposase, resulting in transduction of flanking sequences to new genomic locations. Helraiser transposition generates covalently closed circular intermediates, suggestive of a replicative transposition mechanism, which provides a powerful means to disseminate captured transcriptional regulatory signals across the genome. Indeed, we document the generation of novel transcripts by Helitron promoter capture both experimentally and by transcriptome analysis in bats. Our results provide mechanistic insight into Helitron transposition, and its impact on diversification of gene function by genome shuffling.

Transposons As Tools for Functional Genomics in Vertebrate Models

“…Mutagenic transposon vectors can also be directly introduced into animal models, either by microinjection of the transposon components into early embryos or by mobilizing chromosomally resident transposons upon crossing of transgenic animal stocks encoding the different components of the transposon systems. One recent addition to the transposon toolbox is the Helraiser transposon that has been resurrected from ancient Helitron elements in the bat genome [135]. The fundamental difference to all other transposons that were described in this article is that Helitron elements transpose through a “copy-and-paste” reaction, in which the donor element does not excise, but it generates progeny that integrates elsewhere in the genome.…”

Non-canonical Helitrons in Fusarium oxysporum

“…Grabundzija and others confirmed the ‘end-bypass’ model of gene capture in Helitrons, in which the transposase skips the 3’ terminus and thus includes 3’ flanking DNA sequence in the excised Helitron. Finally, Grabundzija and others demonstrated that canonical Helitrons occur as a circular intermediate [14], as has been observed previously for the Insertion Sequence IS91 in Escherichia coli [23]. Transposition via a circular intermediate can also explain the presence of multiple tandem insertions of truncated Helitrons that have recently been found in plant centromeres [24].…”

“…A recent study using a reconstructed ancestral bat Helitron1 sequence provided important insights into the mechanisms underlying transposition and gene capture in canonical Helitrons [14]. First of all, the authors could demonstrate that Helitrons transpose as single stranded DNA.…”

“…This is congruent with the fact that Helitrons do not cause target site duplications that are associated with double stranded, staggered breaks. Recent biochemical studies show that they transpose via copy-paste rather than cut-and-paste, which explains their high copy number [14]. Helitrons can capture (parts of) genes and thus contribute to the emergence of new genes through combining of different coding and non-coding sequence that have been sequentially captured [4, 6, 7, 14–22].…”

“…Recent biochemical studies show that they transpose via copy-paste rather than cut-and-paste, which explains their high copy number [14]. Helitrons can capture (parts of) genes and thus contribute to the emergence of new genes through combining of different coding and non-coding sequence that have been sequentially captured [4, 6, 7, 14–22]. Grabundzija and others confirmed the ‘end-bypass’ model of gene capture in Helitrons, in which the transposase skips the 3’ terminus and thus includes 3’ flanking DNA sequence in the excised Helitron.…”