Retrotransposon: a versatile player in human preimplantation development and health

More than half of human genome is comprised of transposable elements (TEs), most of which are the retrotransposons (or class I TEs). As the name suggests, retrotransposons propagate via an RNA intermediate that is reversely transcribed and integrated into new genomic loci (a so-called “copy and paste” mechanism). There are three main types of retrotransposons in human genome, including the long terminal repeats (LTRs), non-long terminal repeats (non-LTRs), and SINE-VNTR-Alu (SVA) elements. The LTR elements or endogenous retroviruses (ERVs) are derived from ancient retroviral infections. Over millions of years of evolution, multiple ERV-derived sequences have been fixed in vertebrate genomes, constituting around 8% of human genome. On the other hand, the non-LTRs, including long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), approximately account for 30% of human genome. The LINE-1 (L1) is an autonomous element with the ability to produce the whole enzymatic machinery for mobilization. In contrast, as one type of nonautonomous hominid-specific retrotransposons, SVA can be potentially mobilized in trans by hijacking the retrotransposition machinery produced by autonomous L1 elements. Despite their substantial occupancy of the human genome, most of TEs remain silenced, and have been long referred as “junk DNA” or “fossil records” of ancestral TE invasions. Recently, thanks to the advances in multiomics and genome-editing techniques, accumulating evidence suggests that the “junk DNA” could occasionally have a critical function for the human development and health.