Table 1.
Transposons in the human genome and their influences on health and diseases.
| Classification | Class II |
Class I |
|||
|---|---|---|---|---|---|
| DNA transposons | Retrotransposons |
||||
| LTR retrotransposons | Non-LTR retrotransposons | ||||
| Members (28, 83) | Super families of MITE piggyBac, Merlin, mutator, etc. | Human endogenous retroviruses (HERVs/ERVs) | Solitary LTRs | LINEs (L1, L2, L3) | SINEs (Alu), SVAs, B1s pseudogenes |
| Mammalian apparent LTR retrotransposons (MaLRs) | |||||
| Mechanisms of transposition or replication (28, 83) | Autonomous, “cut and paste” | HERV, autonomous, “copy and paste” (13): (1) retrotransposition, (2) reinfection (complementation in trans) | Autonomous, “copy and paste” (17) | Non-autonomous, Transposition in trans by L1 (18, 19) | |
| MaRL, non-autonomous (15) | |||||
| Reverse transcriptase (83) | (−) | HERV(+) | (−) | (+) | (−) |
| MaLR(−) | |||||
| Number of copies in the genome (×1,000) (5) | 294 | 443 (ERV-class I, 112; class II, 8; class III, 83; Ma LR, 240) | 868 (L1, 516) | 1558 (SVA, 2.76; Alu, 1,090) | |
| Percentage (%) of the genome (5) | 2.84 | 8.29 (HERV, 4.64; MaLR, 3.65) | 20.42 | 13.14 | |
| Structural integrity | (−) | (−) | (+)/(−) | L1 (+) | (+)/(−) |
| Transposing activity in present-day humans (28) | Inactive | Very limited or none (13, 35) | Active (L1 only) | Active with L1 | |
| Time of transposition in human development | None reported | Germline, embryo, and somatic cells (28) | |||
| Recent transpositions/insertions in evolution | ∼37 Myr ago | 8–17 HERV-K insertion the past ∼6 Myr (31) | Not specified | >7500 Transpositions in the past 6 Myr (23) | |
| Impacts of the identified elements on human health and homeostasis | Placenta development | Alteration of cellular gene expression by LTR insertion (∼2 5 loci experimentally characterized) (45, 53) | Gene family generated by SVA through transduction (AMAC, ∼7–14 Myr ago) | ||
| (Syncytin-1/ERVW-1) (55, 56) | |||||
| (Syncytin-2/ERVFRD-1) (57) | Modulation of gene expression by Alu through RNA editing (APOBEC3G, F11R, etc.) (19) | ||||
| Transcriptional activation | Hypomethylation (81) | Hypomethylation (27) | |||
| Trans-activation (37) | Trans-activation (SRY, RUNX3, YY1) | ||||
| Disease-related mechanisms (28, 83) | Transcriptional activation of neighboring gene | Insertional mutagenesis by transposition | |||
| Viral gene expression | Transduction by transposition | ||||
| Recombination (hypothesized) | |||||
| Related disorders | None reported | Hodgkin’s lymphoma (91) (activation of CSF1R by a THE1B LTR) | ∼100 Reported cases by transposition (columns below) (27, 28, 83) | ||
| Hypomethylation detected in malignancy | |||||
| Renal cell carcinoma (89, 90) (HERV-E CT-RCC-8/9, target antigen of CD8+ cells) | |||||
| Other tumors (6, 68) (expression of HERVs) | |||||
| Autoimmune disorders including rheumatoid arthritis, multiple sclerosis, Sjögren’s, and psoriasis (92, 100, 101) (expression of HERVs) | |||||
| Facioscapulohumeral dystrophy (108) (THE1D LTR activation by DUX4) | |||||
| Hemophilia (FVIII, FIX), duchenne muscular dystrophy (DMD), neurofibromatosis type I (NF1), tumors, etc. | Hemophilia (FVIII, FIX), breast cancer (BRCA2), neurofibromatosis type I (NF1), etc. | ||||