Non-long terminal repeat (non-LTR) retrotransposons: mechanisms, recent developments, and unanswered questions

The biological drive to replicate makes it almost inevitable that selfish genetic elements will populate genomes [1]. Indeed, genome sequencing has revealed that single copy genes are often vastly outnumbered by repetitive transposable elements [2-6]. The abundance and distribution of any particular transposon depends on how aggressive the transposon is (how quickly it can multiply in copy number), where the transposon inserts new copies, and how the host responds. Since these factors can vary greatly, the transposon content of each species is unique and virtually impossible to predict a priori. In humans, this number is at least 45% [2].Transposons can be divided into two broad classes: DNA transposons and retrotransposons. DNA transposons replicate via a cut and paste mechanism [7], whereas retrotransposons replicate using an RNA intermediate. Retrotransposons can be further subdivided into long terminal repeat (LTR) and non-LTR retrotransposons. LTR retrotransposons are retroviral-like in structure and mechanism [8]. Non-LTR retrotransposons (also called LINEs, polyA retrotransposons, or target-primed (TP) retrotransposons), as implied by their name, do not contain LTRs and instead take on the likeness of an integrated mRNA. They are ancient genetic elements that have persisted in eukaryotic genomes for hundreds of millions of years [9], and are perhaps best known for their enormous success multiplying in the human genome. Although non-LTR retrotransposons can be parasitized by non-autonomous elements (for example, short interspersed transposable elements (SINEs)), this review will focus on autonomous elements, which encode the protein machinery necessary for their self-mobilization.Full length, autonomous non-LTR retrotransposons typically contain one or two open reading frames (ORFs). The general structure of three model examples, the Bombyx mori R2 element, the human L1 element, and the Drosophila melanogaster I factor, are depicted in Figure 1. Central to ret