Identification and characterization of retro-DNAs, a new type of retrotransposons originated from DNA transposons, in primate genomes

Abstract

Mobile elements (MEs) can be divided into two major classes based on their transposition mechanisms as retrotransposons and DNA transposons. DNA transposons move in the genomes directly in the form of DNA in a cut-and-paste style, while retrotransposons utilize an RNA-intermediate to transpose in a "copy-and-paste" fashion. In addition to the target site duplications (TSDs), a hallmark of transposition shared by both classes, the DNA transposons also carry terminal inverted repeats (TIRs). DNA transposons constitute ~3% of primate genomes and they are thought to be inactive in the recent primate genomes since ~37My ago despite their success during early primate evolution. Retrotransposons can be further divided into Long Terminal Repeat retrotransposons (LTRs), which are characterized by the presence of LTRs at the two ends, and non-LTRs, which lack LTRs. In the primate genomes, LTRs constitute ~9% of genomes and have a low level of ongoing activity, while non-LTR retrotransposons represent the major types of MEs, contributing to ~37% of the genomes with some members being very young and currently active in retrotransposition. The four known types of non-LTR retrotransposons include LINEs, SINEs, SVAs, and processed pseudogenes, all characterized by the presence of a polyA tail and TSDs, which mostly range from 8 to 15 bp in length. All non-LTR retrotransposons are known to utilize the L1-based target-primed reverse transcription (TPRT) machineries for retrotransposition. In this study, we report a new type of non-LTR retrotransposon, which we named as retro-DNAs, to represent DNA transposons by sequence but non-LTR retrotransposons by the transposition mechanism in the recent primate genomes. By using a bioinformatics comparative genomics approach, we identified a total of 1,750 retro-DNAs, which represent 748 unique insertion events in the human genome and nine non-human primate genomes from the ape and monkey groups. These retro-DNAs, mostly as fragments of full-length DNA transposons, carry no TIRs but longer TSDs with ~23.5% also carrying a polyA tail and with their insertion site motifs and TSD length pattern characteristic of non-LTR retrotransposons. These features suggest that these retro-DNAs are DNA transposon sequences likely mobilized by the TPRT mechanism. Further, at least 40% of these retro-DNAs locate to genic regions, presenting significant potentials for impacting gene function. More interestingly, some retro-DNAs, as well as their parent sites, show certain levels of current transcriptional expression, suggesting that they have the potential to create more retro-DNAs in the current primate genomes. The identification of retro-DNAs, despite small in number, reveals a new mechanism in propagating the DNA transposons sequences in the primate genomes with the absence of canonical DNA transposon activity. It also suggests that the L1 TPRT machinery may have the ability to retrotranspose a wider variety of DNA sequences than what we currently know.