RetroSeeker reveals the characteristics, expression, and evolution of a large set of novel retrotransposons

Abstract Retrotransposons are highly prevalent in most animals and account for more than 35% of the human genome. However, the prevalence, biogenesis mechanism and function of retrotransposons remain largely unknown. Here, we developed retroSeeker, a novel computational software that identifies novel retrotransposons from pairwise alignments of genomes and decodes their biogenesis, expression, evolution and potential functions. We discovered that the majority of new retrotransposons exhibit a specific L1 endonuclease cleavage motif, with some motifs precisely located ten nucleotides upstream of the insertion site. We identified that a large number of candidate functional genes might be generated through a retrotransposition mechanism. Importantly, we uncovered previously uncharacterized classes of retrotransposons related to histone genes, mitochondrial genes and vault RNAs. Moreover, we elucidated the tissue-specific expression of retrotransposons and demonstrated their ubiquitous expression in various cancer types. We also revealed the complex evolutionary patterns of retrotransposons and identified numerous species-specific retrotransposition events. Taken together, our findings establish a paradigm for discovering novel classes of retrotransposons and elucidating their new characteristics in any species.