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Abstract
The integration and fixation preferences of DNA transposons, one of the major classes of eukaryotic transposable elements, have never been evaluated comprehensively on a genome-wide scale. Here, we present a detailed study of the distribution of DNA transposons in the human and bat genomes. We studied three groups of DNA transposons that integrated at different evolutionary times: 1) ancient (>40 My) and currently inactive human elements, 2) younger (<40 My) bat elements, and 3) ex vivo integrations of piggyBat and Sleeping Beauty elements in HeLa cells. Although the distribution of ex vivo elements reflected integration preferences, the distribution of human and (to a lesser extent) bat elements was also affected by selection. We used regression techniques (linear, negative binomial, and logistic regression models with multiple predictors) applied to 20-kb and 1-Mb windows to investigate how the genomic landscape in the vicinity of DNA transposons contributes to their integration and fixation. Our models indicate that genomic landscape explains 16-79% of variability in DNA transposon genome-wide distribution. Importantly, we not only confirmed previously identified predictors (e.g., DNA conformation and recombination hotspots) but also identified several novel predictors (e.g., signatures of double-strand breaks and telomere hexamer). Ex vivo integrations showed a bias toward actively transcribed regions. Older DNA transposons were located in genomic regions scarce in most conserved elements-likely reflecting purifying selection. Our study highlights how DNA transposons are integral to the evolution of bat and human genomes, and has implications for the development of DNA transposon assays for gene therapy and mutagenesis applications.
Highlights
Transposable elements (TEs) make up approximately half of the human genome (Lander et al 2001)
Using two ex vivo experimental data sets of piggyBat (Mitra et al 2013) and Sleeping Beauty (SB) (Ammar et al 2012) de novo integrations recovered from HeLa cells, we investigated the genomic landscape of integration for each of these elements using the same regression framework
The increasing availability of genome sequences is allowing researchers to unravel the impact of DNA transposons on the evolution of many species (Dooner and Weil 2007; Feschotte and Pritham 2007)
Summary
Transposable elements (TEs) make up approximately half of the human genome (Lander et al 2001). DNA transposons have not been active for ~40–50 My (Lander et al 2001; Pace and Feschotte 2007) They are known to have been more recently or still active in several other tetrapod species, for example, in green anole lizard and African clawed frog. Mitra et al (2013) showed that the piggyBac1_Ml family (named piggyBat), a member of the cut-and-paste piggyBac superfamily, likely represents the youngest DNA transposon family in the bat genome holding intact coding and cis-acting transposase sequences. They demonstrated transpositional activity of this element in bat, human, and yeast cells
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