Abstract
Transposable elements (TEs) play a significant role in evolution, contributing to genetic variation. However, TE mobilization in somatic cells is not well understood. Here, we address the prevalence of transposition in a somatic tissue, exploiting the Drosophila midgut as a model. Using whole‐genome sequencing of in vivo clonally expanded gut tissue, we have mapped hundreds of high‐confidence somatic TE integration sites genome‐wide. We show that somatic retrotransposon insertions are associated with inactivation of the tumor suppressor Notch, likely contributing to neoplasia formation. Moreover, applying Oxford Nanopore long‐read sequencing technology we provide evidence for tissue‐specific differences in retrotransposition. Comparing somatic TE insertional activity with transcriptomic and small RNA sequencing data, we demonstrate that transposon mobility cannot be simply predicted by whole tissue TE expression levels or by small RNA pathway activity. Finally, we reveal that somatic TE insertions in the adult fly intestine are enriched in genic regions and in transcriptionally active chromatin. Together, our findings provide clear evidence of ongoing somatic transposition in Drosophila and delineate previously unknown features underlying somatic TE mobility in vivo.
Highlights
Transposable elements (TEs) are DNA sequences that shape evolution through their capacity to amplify and mobilize, thereby altering the structural and regulatory landscape of the genome
Somatic TE insertions in the Notch gene identified in spontaneous intestinal neoplasia We have previously shown that somatic mutations occur frequently in intestinal stem cells (ISCs) and that the spontaneous inactivation of a tumor suppressor Notch in male adult ISCs drives the clonal expansion of mutant cells and formation of gut neoplasia (Siudeja et al, 2015)
In order to expand this analysis and better characterize distinct types of somatic mutations that impact adult ISCs, we generated a large dataset of wholegenome paired-end Illumina sequencing of an additional 30 clonal neoplasia from the same genetic background, as well as four clonal neoplasia from DeltaGAL4 UAS-nlsGFP male flies, for a total of 37 clonal samples and matched control head DNA sequenced with an average of 47x coverage (Fig 1A and Table EV1)
Summary
Transposable elements (TEs) are DNA sequences that shape evolution through their capacity to amplify and mobilize, thereby altering the structural and regulatory landscape of the genome. The escape of TEs from silencing allows their propagation in the genome. While de novo TE insertions in the germline are relatively easy to detect as they result in heritable genomic changes that can be detected through sequencing, TE mobility in somatic cells is more difficult to study. The heterogeneity of transposition events within somatic tissues imposes technical challenges as rare TE insertion events affecting a subpopulation of cells often fall below the limits of detection. The degree to which TEs evade silencing and contribute to somatic genome alteration is much less well understood in developing and adult tissues
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