Comparative genomics reveals LINE-1 recombination with diverse RNAs

Long interspersed element-1 (LINE-1, L1) retrotransposons are the most abundant protein-coding transposable elements (TEs) in mammalian genomes and have shaped genome content over 170 million years of evolution. LINE-1 is self-propagating and mobilizes other sequences, including Alu elements. Occasionally, LINE-1 forms chimeric insertions with non-coding RNAs and mRNAs, but there are no comprehensive catalogs of LINE-1 chimeras. To address this, we developed timing mobile element insertions (TiMEstamp), a computational pipeline that leverages multiple sequence alignments (MSAs) to estimate the age of LINE-1 insertions and identify candidate chimeric insertions where an adjacent sequence arrives contemporaneously. With this pipeline, we discovered new chimeric insertions involving small RNAs, Alu elements, and mRNA fragments. Additionally, we saw evidence that LINE-1 loci with defunct promoters can acquire regulatory elements from nearby genes to restore expression and retrotransposition activity. These discoveries highlight the recombinatory potential of LINE-1 RNA with implications for genome evolution, TE domestication, and somatic retrotransposition.