Fig. 1

Human transposable elements. a HERV-K, AluYa5, SVA_F and L1HS (L1 human-specific) are the youngest human ERV, Alu, SVA, and L1 families, respectively. New retrotransposition events are flanked by hallmark target site duplications (TSDs, pink triangles). HERV-K is ~9 kbp in length, contains a tRNA reverse transcription primer binding site (PBS), and encodes overlapping Gag, Pro, Pol, and Env ORFs. Amongst other features, Pol incorporates reverse transcriptase (RT), ribonuclease H (RH), and integrase (IN) activities. AluYa5 (~ 280 bp) is composed of left (L) and right (R) monomers divided by an adenosine-rich region and is followed by a polyadenine tail (A_n). SVA_F (~2 kbp) is a composite element that brings together a variable number of CCCTCT hexamers, an Alu-like sequence, a variable number tandem repeat (VNTR) region and SINE-R, a sequence strongly resembling a portion of the HERV-K Env gene and 3′ LTR. L1HS (~6 kbp) is the only autonomously mobile human TE. It encodes two sense ORFs (ORF1 and ORF2) and an antisense ORF (ORF0) that may boost its mobility [29]. ORF2p possesses endonuclease (EN) and reverse transcriptase (RT) activities. Black arrows indicate known promoter elements. Elements are not depicted to scale. b HERV family statistics [30,31,32]. c HERV retrotransposition model, adapted from [33]. A provirus mRNA is transcribed and translated into a Gag-Pro-Pol fusion protein. Gag is cleaved by Pro to generate a virus-like particle, containing the fusion protein and ERV mRNA. A specific tRNA binds the primer binding site (PBS) to promote reverse transcription, producing a cDNA. The cDNA forms a complex with integrase (IN) to integrate into a new genomic site. d Internal homologous recombination events can occur between 5′ and 3′ LTRs, resulting in loss of the provirus internal region and one LTR, to generate a solo LTR. e Long- and short-read sequencing approaches differ in their ability to discriminate HERV proviral and solo LTR alleles