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. |