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Simplified representation of the life cycle of a retrotransposon

Retrotransposons (also called Class I transposable elements) are mobile elements which move in the host genome by converting their transcribed RNA into DNA through reverse transcription.^[1] Thus, they differ from Class II transposable elements, or DNA transposons, in utilizing an RNA intermediate for the transposition and leaving the transposition donor site unchanged.^[2]

Through reverse transcription, retrotransposons amplify themselves quickly to become abundant in eukaryotic genomes such as maize (49–78%)^[3] and humans (42%).^[4] They are only present in eukaryotes but share features with retroviruses such as HIV, for example, discontinuous reverse transcriptase-mediated extrachromosomal recombination.^[5]^[6]

There are two main types of retrotransposons, long terminal repeats (LTRs) and non-long terminal repeats (non-LTRs). Retrotransposons are classified based on sequence and method of transposition.^[7] Most retrotransposons in the maize genome are LTR, whereas in humans they are mostly non-LTR.

LTR retrotransposons

LTR retrotransposons are characterized by their long terminal repeats (LTRs), which are present at both the 5' and 3' ends of their sequences. These LTRs contain the promoters for these transposable elements (TEs), are essential for TE integration, and can vary in length from just over 100 base pairs (bp) to more than 1,000 bp. On average, LTR retrotransposons span several thousand base pairs, with the largest known examples reaching up to 30 kilobases (kb).

LTRs are highly functional sequences, and for that reason LTR and non-LTR retrotransposons differ greatly in their reverse transcription and integration mechanisms. Non-LTR retrotransposons use a target-primed reverse transcription (TPRT) process, which requires the RNA of the TE to be brought to the cleavage site of the retrotransposon’s integrase, where it is reverse transcribed. In contrast, LTR retrotransposons undergo reverse transcription in the cytoplasm, utilizing two rounds of template switching, and a formation of a pre-integration complex (PIC) composed of double-stranded DNA and an integrase dimer bound to LTRs. This complex then moves into the nucleus for integration into a new genomic location.

LTR retrotransposons typically encode the proteins gag and pol, which may be combined into a single open reading frame (ORF) or separated into distinct ORFs. Similar to retroviruses, the gag protein is essential for capsid assembly and the packaging of the TE's RNA and associated proteins. The pol protein is necessary for reverse transcription and includes these crucial domains: PR (protease), RT (reverse transcriptase), RH (RNase H), and INT (integrase). Additionally, some LTR retrotransposons have an ORF for an envelope (env) protein that is incorporated into the assembled capsid, facilitating attachment to cellular surfaces.

Endogenous retrovirus

An endogenous retrovirus is a retrovirus without virus pathogenic effects that has been integrated into the host genome by inserting their inheritable genetic information into cells that can be passed onto the next generation like a retrotransposon.^[8] Because of this, they share features with retroviruses and retrotransposons. When the retroviral DNA is integrated into the host genome they evolve into endogenous retroviruses that influence eukaryotic genomes. So many endogenous retroviruses have inserted themselves into eukaryotic genomes that they allow insight into biology between viral-host interactions and the role of retrotransposons in evolution and disease. Many retrotransposons share features with endogenous retroviruses, the property of recognising and fusing with the host genome. However, there is a key difference between retroviruses and retrotransposons, which is indicated by the env gene. Although similar to the gene carrying out the same function in retroviruses, the env gene is used to determine whether the gene is retroviral or retrotransposon. If the gene is retroviral it can evolve from a retrotransposon into a retrovirus. They differ by the order of sequences in pol genes. Env genes are found in LTR retrotransposon types Ty1-copia (Pseudoviridae), Ty3-gypsy (Metaviridae) and BEL/Pao.^[9]^[8] They encode glycoproteins on the retrovirus envelope needed for entry into the host cell. Retroviruses can move between cells whereas LTR retrotransposons can only move themselves into the genome of the same cell.^[10] Many vertebrate genes were formed from retroviruses and LTR retrotransposons. One endogenous retrovirus or LTR retrotransposon has the same function and genomic locations in different species, suggesting their role in evolution.^[11]

Non-LTR retrotransposons

Like LTR retrotransposons, non-LTR retrotransposons contain genes for reverse transcriptase, RNA-binding protein, nuclease, and sometimes ribonuclease H domain^[12] but they lack the long terminal repeats. RNA-binding proteins bind the RNA-transposition intermediate and nucleases are enzymes that break phosphodiester bonds between nucleotides in nucleic acids. Instead of LTRs, non-LTR retrotransposons have short repeats that can have an inverted order of bases next to each other aside from direct repeats found in LTR retrotransposons that is just one sequence of bases repeating itself.

Although they are retrotransposons, they cannot carry out reverse transcription using an RNA transposition intermediate in the same way as LTR retrotransposons. Those two key components of the retrotransposon are still necessary but the way they are incorporated into the chemical reactions is different. This is because unlike LTR retrotransposons, non-LTR retrotransposons do not contain sequences that bind tRNA.

They mostly fall into two types – LINEs (Long interspersed nuclear elements) and SINEs (Short interspersed nuclear elements). SVA elements are the exception between the two as they share similarities with both LINEs and SINEs, containing Alu elements and different numbers of the same repeat. SVAs are shorter than LINEs but longer than SINEs.

While historically viewed as "junk DNA", research suggests in some cases, both LINEs and SINEs were incorporated into novel genes to form new functions.^[13]

LINEs

When a LINE is transcribed, the transcript contains an RNA polymerase II promoter that ensures LINEs can be copied into whichever location it inserts itself into. RNA polymerase II is the enzyme that transcribes genes into mRNA transcripts. The ends of LINE transcripts are rich in multiple adenines,^[14] the bases that are added at the end of transcription so that LINE transcripts would not be degraded. This transcript is the RNA transposition intermediate.

The RNA transposition intermediate moves from the nucleus into the cytoplasm for translation. This gives the two coding regions of a LINE that in turn binds back to the RNA it is transcribed from. The LINE RNA then moves back into the nucleus to insert into the eukaryotic genome.

LINEs insert themselves into regions of the eukaryotic genome that are rich in bases AT. At AT regions LINE uses its nuclease to cut one strand of the eukaryotic double-stranded DNA. The adenine-rich sequence in LINE transcript base pairs with the cut strand to flag where the LINE will be inserted with hydroxyl groups. Reverse transcriptase recognises these hydroxyl groups to synthesise LINE retrotransposon where the DNA is cut. Like with LTR retrotransposons, this new inserted LINE contains eukaryotic genome information so it can be copied and pasted into other genomic regions easily. The information sequences are longer and more variable than those in LTR retrotransposons.

Most LINE copies have variable length at the start because reverse transcription usually stops before DNA synthesis is complete. In some cases this causes RNA polymerase II promoter to be lost so LINEs cannot transpose further.^[15]

Human L1

LINE-1 (L1) retrotransposons make up a significant portion of the human genome, with an estimated 500,000 copies per genome. Genes encoding for human LINE1 usually have their transcription inhibited by methyl groups binding to its DNA carried out by PIWI proteins and enzymes DNA methyltransferases. L1 retrotransposition can disrupt the nature of genes transcribed by pasting themselves inside or near genes which could in turn lead to human disease. LINE1s can only retrotranspose in some cases to form different chromosome structures contributing to differences in genetics between individuals.^[17] There is an estimate of 80–100 active L1s in the reference genome of the Human Genome Project, and an even smaller number of L1s within those active L1s retrotranspose often. L1 insertions have been associated with tumorigenesis by activating cancer-related genes oncogenes and diminishing tumor suppressor genes.

Each human LINE1 contains two regions from which gene products can be encoded. The first coding region contains a leucine zipper protein involved in protein-protein interactions and a protein that binds to the terminus of nucleic acids. The second coding region has a purine/pyrimidine nuclease, reverse transcriptase and protein rich in amino acids cysteines and histidines. The end of the human LINE1, as with other retrotransposons is adenine-rich.^[18]^[19]^[20]

Human L1 actively retrotransposes in the human genome. A recent study identified 1,708 somatic L1 retrotransposition events, especially in colorectal epithelial cells. These events occur from early embryogenesis and retrotransposition rate is substantially increased during colorectal tumourigenesis.^[21]

SINEs

SINEs are much shorter (300bp) than LINEs.^[22] They share similarity with genes transcribed by RNA polymerase II, the enzyme that transcribes genes into mRNA transcripts, and the initiation sequence of RNA polymerase III, the enzyme that transcribes genes into ribosomal RNA, tRNA and other small RNA molecules.^[23] SINEs such as mammalian MIR elements have tRNA gene at the start and adenine-rich at the end like in LINEs.

SINEs do not encode a functional reverse transcriptase protein and rely on other mobile transposons, especially LINEs.^[24] SINEs exploit LINE transposition components despite LINE-binding proteins prefer binding to LINE RNA. SINEs cannot transpose by themselves because they cannot encode SINE transcripts. They usually consist of parts derived from tRNA and LINEs. The tRNA portion contains an RNA polymerase III promoter which the same kind of enzyme as RNA polymerase II. This makes sure the LINE copies would be transcribed into RNA for further transposition. The LINE component remains so LINE-binding proteins can recognise the LINE part of the SINE.

Alu elements

Alus are the most common SINE in primates. They are approximately 350 base pairs long, do not encode proteins and can be recognized by the restriction enzyme AluI (hence the name). Their distribution may be important in some genetic diseases and cancers. Copy and pasting Alu RNA requires the Alu's adenine-rich end and the rest of the sequence bound to a signal. The signal-bound Alu can then associate with ribosomes. LINE RNA associates on the same ribosomes as the Alu. Binding to the same ribosome allows Alus of SINEs to interact with LINE. This simultaneous translation of Alu element and LINE allows SINE copy and pasting.

SVA elements

SVA elements are present at lower levels than SINES and LINEs in humans. The starts of SVA and Alu elements are similar, followed by repeats and an end similar to endogenous retrovirus. LINEs bind to sites flanking SVA elements to transpose them. SVA are one of the youngest transposons in great apes genome and among the most active and polymorphic in the human population. SVA was created by a fusion between an Alu element, a VNTR (variable number tandem repeat), and an LTR fragment.^[25]

Role in human disease

Retrotransposons ensure they are not lost by chance by occurring only in cell genetics that can be passed on from one generation to the next from parent gametes. However, LINEs can transpose into the human embryo cells that eventually develop into the nervous system, raising the question whether this LINE retrotransposition affects brain function. LINE retrotransposition is also a feature of several cancers, but it is unclear whether retrotransposition itself causes cancer instead of just a symptom. Uncontrolled retrotransposition is bad for both the host organism and retrotransposons themselves so they have to be regulated. Retrotransposons are regulated by RNA interference. RNA interference is carried out by a bunch of short non-coding RNAs. The short non-coding RNA interacts with protein Argonaute to degrade retrotransposon transcripts and change their DNA histone structure to reduce their transcription.

Role in evolution

LTR retrotransposons came about later than non-LTR retrotransposons, possibly from an ancestral non-LTR retrotransposon acquiring an integrase from a DNA transposon. Retroviruses gained additional properties to their virus envelopes by taking the relevant genes from other viruses using the power of LTR retrotransposon.

Due to their retrotransposition mechanism, retrotransposons amplify in number quickly, composing 40% of the human genome. The insertion rates for LINE1, Alu and SVA elements are 1/200 – 1/20, 1/20 and 1/900 respectively. The LINE1 insertion rates have varied a lot over the past 35 million years, so they indicate points in genome evolution.

Notably a large number of 100 kilobases in the maize genome show variety due to the presence or absence of retrotransposons. However since maize is unusual genetically as compared to other plants it cannot be used to predict retrotransposition in other plants.

Mutations caused by retrotransposons include:

Gene inactivation
Changing gene regulation
Changing gene products
Acting as DNA repair sites

Role in biotechnology

References

^ Dombroski BA, Feng Q, Mathias SL, Sassaman DM, Scott AF, Kazazian HH, Boeke JD (July 1994). "An in vivo assay for the reverse transcriptase of human retrotransposon L1 in Saccharomyces cerevisiae". Molecular and Cellular Biology. 14 (7): 4485–92. doi:10.1128/mcb.14.7.4485. PMC 358820. PMID 7516468.
^ Craig, Nancy Lynn (2015). Mobile DNA III. Washington (D.C.): ASM press. ISBN 9781555819200.
^ SanMiguel P, Bennetzen JL (1998). "Evidence that a recent increase in maize genome size was caused by the massive amplification of intergene retrotranposons". Annals of Botany. 82 (Suppl A): 37–44. Bibcode:1998AnBot..82...37S. doi:10.1006/anbo.1998.0746.
^ Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. (February 2001). "Initial sequencing and analysis of the human genome". Nature. 409 (6822): 860–921. Bibcode:2001Natur.409..860L. doi:10.1038/35057062. hdl:2027.42/62798. PMID 11237011.
^ Sanchez DH, Gaubert H, Drost HG, Zabet NR, Paszkowski J (November 2017). "High-frequency recombination between members of an LTR retrotransposon family during transposition bursts". Nature Communications. 8 (1): 1283. Bibcode:2017NatCo...8.1283S. doi:10.1038/s41467-017-01374-x. PMC 5668417. PMID 29097664.
^ Drost HG, Sanchez DH (December 2019). "Becoming a Selfish Clan: Recombination Associated to Reverse-Transcription in LTR Retrotransposons". Genome Biology and Evolution. 11 (12): 3382–3392. doi:10.1093/gbe/evz255. PMC 6894440. PMID 31755923.
^ Xiong Y, Eickbush TH (October 1990). "Origin and evolution of retroelements based upon their reverse transcriptase sequences". The EMBO Journal. 9 (10): 3353–62. doi:10.1002/j.1460-2075.1990.tb07536.x. PMC 552073. PMID 1698615.
^ ^a ^b Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell A, Leroy P, Morgante M, Panaud O, Paux E, SanMiguel P, Schulman AH (December 2007). "A unified classification system for eukaryotic transposable elements". Nature Reviews. Genetics. 8 (12): 973–82. doi:10.1038/nrg2165. PMID 17984973. S2CID 32132898.
^ Copeland CS, Mann VH, Morales ME, Kalinna BH, Brindley PJ (February 2005). "The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements". BMC Evolutionary Biology. 5 (1): 20. doi:10.1186/1471-2148-5-20. PMC 554778. PMID 15725362.
^ Havecker ER, Gao X, Voytas DF (18 May 2004). "The diversity of LTR retrotransposons". Genome Biology. 5 (225): 225. doi:10.1186/gb-2004-5-6-225. PMC 463057. PMID 15186483.
^ Naville M, Warren IA, Haftek-Terreau Z, Chalopin D, Brunet F, Levin P, Galiana D, Volff JN (17 February 2016). "Not so bad after all: retroviruses and long terminal repeat retrotransposons as a source of new genes in vertebrates". Clinical Microbiology and Infection. 22 (4): 312–323. doi:10.1016/j.cmi.2016.02.001. PMID 26899828.
^ Yadav VP, Mandal PK, Rao DN, Bhattacharya S (December 2009). "Characterization of the restriction enzyme-like endonuclease encoded by the Entamoeba histolytica non-long terminal repeat retrotransposon EhLINE1". The FEBS Journal. 276 (23): 7070–82. doi:10.1111/j.1742-4658.2009.07419.x. PMID 19878305. S2CID 30791213.
^ Santangelo AM, de Souza FS, Franchini LF, Bumaschny VF, Low MJ, Rubinstein M (October 2007). "Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene". PLOS Genetics. 3 (10): 1813–26. doi:10.1371/journal.pgen.0030166. PMC 2000970. PMID 17922573.
^ Liang KH, Yeh CT (May 2013). "A gene expression restriction network mediated by sense and antisense Alu sequences located on protein-coding messenger RNAs". BMC Genomics. 14: 325. doi:10.1186/1471-2164-14-325. PMC 3655826. PMID 23663499.
^ Singer MF (March 1982). "SINEs and LINEs: highly repeated short and long interspersed sequences in mammalian genomes". Cell. 28 (3): 433–4. doi:10.1016/0092-8674(82)90194-5. PMID 6280868. S2CID 22129236.
^ Walter M (2015). "Transposon regulation upon dynamic loss of DNA methylation (PDF Download Available)". ResearchGate. doi:10.13140/rg.2.2.18747.21286.
^ Chueh AC, Northrop EL, Brettingham-Moore KH, Choo KH, Wong LH (January 2009). Bickmore WA (ed.). "LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin". PLOS Genetics. 5 (1): e1000354. doi:10.1371/journal.pgen.1000354. PMC 2625447. PMID 19180186.
^ Doucet AJ, Hulme AE, Sahinovic E, Kulpa DA, Moldovan JB, Kopera HC, Athanikar JN, Hasnaoui M, Bucheton A, Moran JV, Gilbert N (October 2010). "Characterization of LINE-1 ribonucleoprotein particles". PLOS Genetics. 6 (10): e1001150. doi:10.1371/journal.pgen.1001150. PMC 2951350. PMID 20949108.
^ Denli AM, Narvaiza I, Kerman BE, Pena M, Benner C, Marchetto MC, Diedrich JK, Aslanian A, Ma J, Moresco JJ, Moore L, Hunter T, Saghatelian A, Gage FH (October 2015). "Primate-specific ORF0 contributes to retrotransposon-mediated diversity". Cell. 163 (3): 583–93. doi:10.1016/j.cell.2015.09.025. PMID 26496605. S2CID 10525450.
^ Ohshima K, Okada N (2005). "SINEs and LINEs: symbionts of eukaryotic genomes with a common tail". Cytogenetic and Genome Research. 110 (1–4): 475–90. doi:10.1159/000084981. PMID 16093701. S2CID 42841487.
^ Nam, Chang Hyun; Youk, Jeonghwan; Kim, Jeong Yeon; Lim, Joonoh; Park, Jung Woo; Oh, Soo A; Lee, Hyun Jung; Park, Ji Won; Won, Hyein; Lee, Yunah; Jeong, Seung-Yong; Lee, Dong-Sung; Oh, Ji Won; Han, Jinju; Lee, Junehawk (2023-05-18). "Widespread somatic L1 retrotransposition in normal colorectal epithelium". Nature. 617 (7961): 540–547. Bibcode:2023Natur.617..540N. doi:10.1038/s41586-023-06046-z. ISSN 0028-0836. PMC 10191854. PMID 37165195.
^ Stansfield WD, King RC (1997). A dictionary of genetics (5th ed.). Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-509441-1.
^ Kramerov DA, Vassetzky NS (2005). Short retroposons in eukaryotic genomes. International Review of Cytology. Vol. 247. pp. 165–221. doi:10.1016/s0074-7696(05)47004-7. PMID 16344113.
^ Dewannieux M, Esnault C, Heidmann T (September 2003). "LINE-mediated retrotransposition of marked Alu sequences". Nature Genetics. 35 (1): 41–8. doi:10.1038/ng1223. PMID 12897783. S2CID 32151696.
^ Wells, JN; Feschotte, C (23 November 2020). "A Field Guide to Eukaryotic Transposable Elements". Annual Review of Genetics. 54: 539–561. doi:10.1146/annurev-genet-040620-022145. PMC 8293684. PMID 32955944.

[1] Dombroski BA, Feng Q, Mathias SL, Sassaman DM, Scott AF, Kazazian HH, Boeke JD (July 1994). "An in vivo assay for the reverse transcriptase of human retrotransposon L1 in Saccharomyces cerevisiae". Molecular and Cellular Biology. 14 (7): 4485–92. doi:10.1128/mcb.14.7.4485. PMC 358820. PMID 7516468.

[2] Craig, Nancy Lynn (2015). Mobile DNA III. Washington (D.C.): ASM press. ISBN 9781555819200.

[SanMiguelandBennetzen-3] SanMiguel P, Bennetzen JL (1998). "Evidence that a recent increase in maize genome size was caused by the massive amplification of intergene retrotranposons". Annals of Botany. 82 (Suppl A): 37–44. Bibcode:1998AnBot..82...37S. doi:10.1006/anbo.1998.0746.

[Landeretal-4] Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. (February 2001). "Initial sequencing and analysis of the human genome". Nature. 409 (6822): 860–921. Bibcode:2001Natur.409..860L. doi:10.1038/35057062. hdl:2027.42/62798. PMID 11237011.

[5] Sanchez DH, Gaubert H, Drost HG, Zabet NR, Paszkowski J (November 2017). "High-frequency recombination between members of an LTR retrotransposon family during transposition bursts". Nature Communications. 8 (1): 1283. Bibcode:2017NatCo...8.1283S. doi:10.1038/s41467-017-01374-x. PMC 5668417. PMID 29097664.

[6] Drost HG, Sanchez DH (December 2019). "Becoming a Selfish Clan: Recombination Associated to Reverse-Transcription in LTR Retrotransposons". Genome Biology and Evolution. 11 (12): 3382–3392. doi:10.1093/gbe/evz255. PMC 6894440. PMID 31755923.

[7] Xiong Y, Eickbush TH (October 1990). "Origin and evolution of retroelements based upon their reverse transcriptase sequences". The EMBO Journal. 9 (10): 3353–62. doi:10.1002/j.1460-2075.1990.tb07536.x. PMC 552073. PMID 1698615.

[wicker-8] Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell A, Leroy P, Morgante M, Panaud O, Paux E, SanMiguel P, Schulman AH (December 2007). "A unified classification system for eukaryotic transposable elements". Nature Reviews. Genetics. 8 (12): 973–82. doi:10.1038/nrg2165. PMID 17984973. S2CID 32132898.

[Copland-9] Copeland CS, Mann VH, Morales ME, Kalinna BH, Brindley PJ (February 2005). "The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements". BMC Evolutionary Biology. 5 (1): 20. doi:10.1186/1471-2148-5-20. PMC 554778. PMID 15725362.

[LTR_retrotransposon_diversity-10] Havecker ER, Gao X, Voytas DF (18 May 2004). "The diversity of LTR retrotransposons". Genome Biology. 5 (225): 225. doi:10.1186/gb-2004-5-6-225. PMC 463057. PMID 15186483.

[vertebrate_new_genes-11] Naville M, Warren IA, Haftek-Terreau Z, Chalopin D, Brunet F, Levin P, Galiana D, Volff JN (17 February 2016). "Not so bad after all: retroviruses and long terminal repeat retrotransposons as a source of new genes in vertebrates". Clinical Microbiology and Infection. 22 (4): 312–323. doi:10.1016/j.cmi.2016.02.001. PMID 26899828.

[12] Yadav VP, Mandal PK, Rao DN, Bhattacharya S (December 2009). "Characterization of the restriction enzyme-like endonuclease encoded by the Entamoeba histolytica non-long terminal repeat retrotransposon EhLINE1". The FEBS Journal. 276 (23): 7070–82. doi:10.1111/j.1742-4658.2009.07419.x. PMID 19878305. S2CID 30791213.

[Santangelo-13] Santangelo AM, de Souza FS, Franchini LF, Bumaschny VF, Low MJ, Rubinstein M (October 2007). "Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene". PLOS Genetics. 3 (10): 1813–26. doi:10.1371/journal.pgen.0030166. PMC 2000970. PMID 17922573.

[Liang2013-14] Liang KH, Yeh CT (May 2013). "A gene expression restriction network mediated by sense and antisense Alu sequences located on protein-coding messenger RNAs". BMC Genomics. 14: 325. doi:10.1186/1471-2164-14-325. PMC 3655826. PMID 23663499.

[Singer-15] Singer MF (March 1982). "SINEs and LINEs: highly repeated short and long interspersed sequences in mammalian genomes". Cell. 28 (3): 433–4. doi:10.1016/0092-8674(82)90194-5. PMID 6280868. S2CID 22129236.

[:0-16] Walter M (2015). "Transposon regulation upon dynamic loss of DNA methylation (PDF Download Available)". ResearchGate. doi:10.13140/rg.2.2.18747.21286.

[17] Chueh AC, Northrop EL, Brettingham-Moore KH, Choo KH, Wong LH (January 2009). Bickmore WA (ed.). "LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin". PLOS Genetics. 5 (1): e1000354. doi:10.1371/journal.pgen.1000354. PMC 2625447. PMID 19180186.

[pmid20949108-18] Doucet AJ, Hulme AE, Sahinovic E, Kulpa DA, Moldovan JB, Kopera HC, Athanikar JN, Hasnaoui M, Bucheton A, Moran JV, Gilbert N (October 2010). "Characterization of LINE-1 ribonucleoprotein particles". PLOS Genetics. 6 (10): e1001150. doi:10.1371/journal.pgen.1001150. PMC 2951350. PMID 20949108.

[19] Denli AM, Narvaiza I, Kerman BE, Pena M, Benner C, Marchetto MC, Diedrich JK, Aslanian A, Ma J, Moresco JJ, Moore L, Hunter T, Saghatelian A, Gage FH (October 2015). "Primate-specific ORF0 contributes to retrotransposon-mediated diversity". Cell. 163 (3): 583–93. doi:10.1016/j.cell.2015.09.025. PMID 26496605. S2CID 10525450.

[20] Ohshima K, Okada N (2005). "SINEs and LINEs: symbionts of eukaryotic genomes with a common tail". Cytogenetic and Genome Research. 110 (1–4): 475–90. doi:10.1159/000084981. PMID 16093701. S2CID 42841487.

[21] Nam, Chang Hyun; Youk, Jeonghwan; Kim, Jeong Yeon; Lim, Joonoh; Park, Jung Woo; Oh, Soo A; Lee, Hyun Jung; Park, Ji Won; Won, Hyein; Lee, Yunah; Jeong, Seung-Yong; Lee, Dong-Sung; Oh, Ji Won; Han, Jinju; Lee, Junehawk (2023-05-18). "Widespread somatic L1 retrotransposition in normal colorectal epithelium". Nature. 617 (7961): 540–547. Bibcode:2023Natur.617..540N. doi:10.1038/s41586-023-06046-z. ISSN 0028-0836. PMC 10191854. PMID 37165195.

[Dictionary-22] Stansfield WD, King RC (1997). A dictionary of genetics (5th ed.). Oxford [Oxfordshire]: Oxford University Press. ISBN 978-0-19-509441-1.

[23] Kramerov DA, Vassetzky NS (2005). Short retroposons in eukaryotic genomes. International Review of Cytology. Vol. 247. pp. 165–221. doi:10.1016/s0074-7696(05)47004-7. PMID 16344113.

[24] Dewannieux M, Esnault C, Heidmann T (September 2003). "LINE-mediated retrotransposition of marked Alu sequences". Nature Genetics. 35 (1): 41–8. doi:10.1038/ng1223. PMID 12897783. S2CID 32151696.

[pmid32955944-25] Wells, JN; Feschotte, C (23 November 2020). "A Field Guide to Eukaryotic Transposable Elements". Annual Review of Genetics. 54: 539–561. doi:10.1146/annurev-genet-040620-022145. PMC 8293684. PMID 32955944.

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@@ Line 1: / Line 1: @@
+{{short description|Type of genetic component}}
-[[File:Retrotransposons.png|right|Simplified representation of the life cycle of a retrotransposon|440px]]
+<span class="plainlinks"></span>[[File:Retrotransposons.png|thumb|right|440px|Simplified representation of the life cycle of a retrotransposon]]
+'''Retrotransposons''' (also called '''Class I transposable elements''') are [[transposable element|mobile elements]] which move in the host genome by converting their transcribed RNA into DNA through [[reverse transcription]].<ref>{{cite journal | vauthors = Dombroski BA, Feng Q, Mathias SL, Sassaman DM, Scott AF, Kazazian HH, Boeke JD | title = An in vivo assay for the reverse transcriptase of human retrotransposon L1 in Saccharomyces cerevisiae | journal = Molecular and Cellular Biology | volume = 14 | issue = 7 | pages = 4485–92 | date = July 1994 | pmid = 7516468 | pmc = 358820 | doi = 10.1128/mcb.14.7.4485 }}</ref> Thus, they differ from Class II transposable elements, or DNA transposons, in utilizing an RNA intermediate for the transposition and leaving the transposition donor site unchanged.<ref>{{cite book |last1=Craig |first1=Nancy Lynn |title=Mobile DNA III |date=2015 |publisher=ASM press |location=Washington (D.C.) |isbn=9781555819200}}</ref>
-'''Retrotransposons''' (also called transposons via RNA intermediates) are [[Genetics|genetic]] elements that can [[Amplification (molecular biology)#Gene duplication as amplification|amplify]] themselves in a [[genome]] and are ubiquitous components of the [[DNA]] of many [[Eukaryote|eukaryotic]] organisms. These DNA sequences use a "copy-and-paste" mechanism, whereby they are first [[Transcription (biology)|transcribed]] into [[RNA]], then converted back into identical DNA sequences using [[reverse transcription]], and these sequences are then inserted into the genome at target sites.
+Through reverse transcription, retrotransposons amplify themselves quickly to become abundant in [[eukaryote|eukaryotic]] genomes such as [[maize]] (49–78%)<ref name="SanMiguelandBennetzen">{{cite journal |vauthors=SanMiguel P, Bennetzen JL |title=Evidence that a recent increase in maize genome size was caused by the massive amplification of intergene retrotranposons |journal=Annals of Botany |volume=82 |issue=Suppl A |pages=37–44 |year=1998 |doi=10.1006/anbo.1998.0746|doi-access=free |bibcode=1998AnBot..82...37S }}</ref> and humans (42%).<ref name="Landeretal">{{cite journal | vauthors = Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, etal | title = Initial sequencing and analysis of the human genome | journal = Nature | volume = 409 | issue = 6822 | pages = 860–921 | date = February 2001 | pmid = 11237011 | doi = 10.1038/35057062 | bibcode = 2001Natur.409..860L | doi-access = free | hdl = 2027.42/62798 | hdl-access = free }}</ref> They are only present in eukaryotes but share features with [[retrovirus]]es such as [[HIV]], for example, discontinuous [[reverse transcriptase]]-mediated extrachromosomal recombination.<ref>{{cite journal | vauthors = Sanchez DH, Gaubert H, Drost HG, Zabet NR, Paszkowski J | title = High-frequency recombination between members of an LTR retrotransposon family during transposition bursts | journal = Nature Communications | volume = 8 | issue = 1 | pages = 1283 | date = November 2017 | pmid = 29097664 | pmc = 5668417 | doi = 10.1038/s41467-017-01374-x | bibcode = 2017NatCo...8.1283S }}</ref><ref>{{cite journal | vauthors = Drost HG, Sanchez DH | title = Becoming a Selfish Clan: Recombination Associated to Reverse-Transcription in LTR Retrotransposons | journal = Genome Biology and Evolution | volume = 11 | issue = 12 | pages = 3382–3392 | date = December 2019 | pmid = 31755923 | pmc = 6894440 | doi = 10.1093/gbe/evz255 }}</ref>
-Retrotransposons form one of the two subclasses of [[transposon]]s, where the others are [[Transposable element#Class II .28DNA transposons.29|DNA transposons]], which does not involve an RNA intermediate.
+There are two main types of retrotransposons, [[long terminal repeat]]s (LTRs) and non-long terminal repeats (non-LTRs). Retrotransposons are classified based on sequence and method of transposition.<ref>{{cite journal | vauthors = Xiong Y, Eickbush TH | title = Origin and evolution of retroelements based upon their reverse transcriptase sequences | journal = The EMBO Journal | volume = 9 | issue = 10 | pages = 3353–62 | date = October 1990 | pmid = 1698615 | pmc = 552073 | doi = 10.1002/j.1460-2075.1990.tb07536.x }}</ref> Most retrotransposons in the maize genome are LTR, whereas in humans they are mostly non-LTR.
-Retrotransposons are particularly abundant in plants, where they are often a principal component of nuclear DNA. In [[maize]], 49–78% of the genome is made up of retrotransposons.<ref name="SanMiguelandBennetzen">{{cite journal |vauthors=SanMiguel P, Bennetzen JL |title=Evidence that a recent increase in maize genome size was caused by the massive amplification of intergene retrotranposons |journal=Annals of Botany |volume=82 |issue=Suppl A |pages=37–44 |year=1998 |url=http://aob.oxfordjournals.org/cgi/reprint/82/suppl_1/37.pdf |doi=10.1006/anbo.1998.0746}}</ref> In wheat, about 90% of the genome consists of repeated sequences and 68% of transposable elements.<ref name="LiandGill">{{cite journal |vauthors=Li W, Zhang P, Fellers JP, Friebe B, Gill BS |title=Sequence composition, organization, and evolution of the core Triticeae genome |journal=Plant J. |volume=40 |issue=4 |pages=500–11 |date=November 2004 |pmid=15500466 |doi=10.1111/j.1365-313X.2004.02228.x |url=http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-313X.2004.02228.x}}</ref> In mammals, almost half the genome (45% to 48%) is transposons or remnants of transposons. Around 42% of the human genome is made up of retrotransposons, while DNA transposons account for about 2–3%.<ref name="Landeretal">{{cite journal  |vauthors=Lander ES, Linton LM, Birren B, etal |title=Initial sequencing and analysis of the human genome |journal=Nature |volume=409 |issue=6822 |pages=860–921 |date=February 2001 |pmid=11237011 |doi=10.1038/35057062 |url=http://www.nature.com/nature/journal/v409/n6822/full/409860a0.html}}</ref>
+==LTR retrotransposons==
-==Biological activity==
+{{Main article|LTR retrotransposon}}
-The retrotransposons' [[DNA replication|replicative]] mode of [[Transposition (genetics)|transposition]] by means of an RNA intermediate rapidly increases the copy numbers of elements and thereby can increase [[genome]] size. Like DNA [[transposable elements]] (class II transposons), retrotransposons can induce [[mutation]]s by [[insertion (genetics)|inserting]] near or within genes. Furthermore, retrotransposon-induced mutations are relatively stable, because the sequence at the insertion site is retained as they transpose via the replication mechanism.
-Retrotransposons copy themselves to [[RNA]] and then back to [[DNA]] that may integrate back to the genome. The second step of forming DNA may be carried out by a [[reverse transcriptase]], which the retrotransposon encodes.<ref>{{cite journal  |vauthors=Dombroski BA, Feng Q, Mathias SL, etal |title=An in vivo assay for the reverse transcriptase of human retrotransposon L1 in Saccharomyces cerevisiae |journal=Mol. Cell. Biol. |volume=14 |issue=7 |pages=4485–92 |date=July 1994 |pmid=7516468 |pmc=358820 |doi=10.1128/mcb.14.7.4485}}</ref> Transposition and survival of retrotransposons within the host genome are possibly regulated both by retrotransposon- and host-encoded factors, to avoid deleterious effects on host and retrotransposon as well. The understanding of how retrotransposons and their hosts' genomes have co-evolved mechanisms to regulate transposition, insertion specificities, and mutational outcomes in order to optimize each other's survival is still in its infancy.
+LTR retrotransposons are characterized by their long terminal repeats (LTRs), which are present at both the 5' and 3' ends of their sequences. These LTRs contain the promoters for these transposable elements (TEs), are essential for TE integration, and can vary in length from just over 100 base pairs (bp) to more than 1,000 bp. On average, LTR retrotransposons span several thousand base pairs, with the largest known examples reaching up to 30 kilobases (kb).
-Because of accumulated mutations, most retrotransposons are no longer able to retrotranspose.
+LTRs are highly functional sequences, and for that reason LTR and non-LTR retrotransposons differ greatly in their reverse transcription and integration mechanisms. Non-LTR retrotransposons use a [[Long interspersed nuclear element#Propagation|target-primed reverse transcription]] (TPRT) process, which requires the RNA of the TE to be brought to the cleavage site of the retrotransposon’s integrase, where it is reverse transcribed. In contrast, LTR retrotransposons undergo reverse transcription in the cytoplasm, utilizing two rounds of template switching, and a formation of a pre-integration complex (PIC) composed of double-stranded DNA and an integrase dimer bound to LTRs. This complex then moves into the nucleus for integration into a new genomic location.
-==Types of retrotransposons==
-Retrotransposons, also known as class I [[transposable elements]], consist of two subclasses, the [[long terminal repeat]] (LTR) and the [[Retrotransposon#Non-LTR retrotransposons|non-LTR retrotransposons]]. Classification into these subclasses is based on the phylogeny of the reverse transcriptase,<ref>{{cite journal|last1=Xiong|first1=Y|last2=Eickbush|first2=TH|title=Origin and evolution of retroelements based upon their reverse transcriptase sequences.|journal=The EMBO Journal|date=October 1990|volume=9|issue=10|pages=3353–62|pmid=1698615|pmc=552073}}</ref> which goes in line with structural differences, such as presence/absence of long terminal repeats as well as number and types of open reading frames, encoding domains and target site duplication lengths.
+LTR retrotransposons typically encode the proteins [[Group-specific antigen|gag]] and [[Pol (HIV)|pol]], which may be combined into a single [[open reading frame]] (ORF) or separated into distinct ORFs. Similar to retroviruses, the gag protein is essential for capsid assembly and the packaging of the TE's RNA and associated proteins. The pol protein is necessary for reverse transcription and includes these crucial domains: PR (protease), RT (reverse transcriptase), RH ([[Ribonuclease H|RNase H]]), and INT (integrase). Additionally, some LTR retrotransposons have an ORF for an envelope ([[Env (gene)|env]]) protein that is incorporated into the assembled capsid, facilitating attachment to cellular surfaces.
-===LTR retrotransposons===
-LTR retrotransposons have [[Direct repeat|direct]] LTRs that range from ~100 bp to over 5 kb in size. LTR retrotransposons are further sub-classified into the Ty1-''copia''-like ([[Pseudoviridae]]), Ty3-''gypsy''-like ([[Metaviridae]]), and BEL-Pao-like groups based on both their degree of sequence similarity and the order of encoded gene products. Ty1-''copia'' and Ty3-''gypsy'' groups of retrotransposons are commonly found in high copy number (up to a few million copies per [[haploid]] [[cell nucleus|nucleus]]) in animals, fungi, protista, and plants genomes. BEL-Pao like elements have so far only been found in animals.<ref name=Copland>{{cite journal |vauthors=Copeland CS, Mann VH, Morales ME, Kalinna BH, Brindley PJ |title=The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements |journal=BMC Evol. Biol. |volume=5 |pages=20 |year=2005 |pmid=15725362 |pmc=554778 |doi=10.1186/1471-2148-5-20 |issue=1}}</ref><ref name=wicker>{{cite journal  |vauthors=Wicker T, Sabot F, Hua-Van A, etal |title=A unified classification system for eukaryotic transposable elements |journal=Nat. Rev. Genet. |volume=8 |issue=12 |pages=973–82 |date=December 2007 |pmid=17984973 |doi=10.1038/nrg2165 }}</ref> Although [[retrovirus]]es are often classified separately, they share many features with LTR retrotransposons. A major difference with Ty1-''copia'' and Ty3-''gypsy'' retrotransposons is that retroviruses have an Envelope protein (ENV). A retrovirus can be transformed into an LTR retrotransposon through inactivation or deletion of the domains that enable extracellular mobility. If such a retrovirus infects and subsequently inserts itself in the genome in germ line cells, it may become transmitted vertically and become an Endogenous Retrovirus (ERV).<ref name="wicker"/> Endogenous retroviruses make up about 8% of the human genome and approximately 10% of the mouse genome.<ref>{{cite journal |vauthors=McCarthy EM, McDonald JF |title=Long terminal repeat retrotransposons of Mus musculus |journal=Genome Biol. |volume=5 |issue=3 |pages=R14 |year=2004 |pmid=15003117 |pmc=395764 |doi=10.1186/gb-2004-5-3-r14 |url=http://genomebiology.com/2004/5/3/R14}}</ref>
+==Endogenous retrovirus==
-In plant genomes, LTR retrotransposons are the major repetitive sequence class, e.g. able to constitute more than 75%  of the maize genome.<ref>{{cite journal|last1=Baucom|first1=RS|last2=Estill|first2=JC|last3=Chaparro|first3=C|last4=Upshaw|first4=N|last5=Jogi|first5=A|last6=Deragon|first6=JM|last7=Westerman|first7=RP|last8=Sanmiguel|first8=PJ|last9=Bennetzen|first9=JL|title=Exceptional diversity, non-random distribution, and rapid evolution of retroelements in the B73 maize genome.|journal=PLoS Genetics|date=November 2009|volume=5|issue=11|pages=e1000732|pmid=19936065|doi=10.1371/journal.pgen.1000732|pmc=2774510}}</ref>
+{{Main article |Endogenous retrovirus}}
+An endogenous retrovirus is a retrovirus without virus pathogenic effects that has been integrated into the host genome by inserting their inheritable genetic information into cells that can be passed onto the next generation like a retrotransposon.<ref name="wicker" />  Because of this, they share features with retroviruses and retrotransposons. When the retroviral DNA is integrated into the host genome they evolve into endogenous retroviruses that influence eukaryotic genomes. So many endogenous retroviruses have inserted themselves into eukaryotic genomes that they allow insight into biology between viral-host interactions and the role of retrotransposons in evolution and disease.
+Many retrotransposons share features with endogenous retroviruses, the property of recognising and fusing with the host genome. However, there is a key difference between retroviruses and retrotransposons, which is indicated by the env gene. Although similar to the gene carrying out the same function in retroviruses, the env gene is used to determine whether the gene is retroviral or retrotransposon. If the gene is retroviral it can evolve from a retrotransposon into a retrovirus. They differ by the order of sequences in pol genes. Env genes are found in LTR retrotransposon types Ty1-copia ([[Pseudoviridae]]), Ty3-gypsy ([[Metaviridae]]) and BEL/Pao.<ref name="Copland">{{cite journal | vauthors = Copeland CS, Mann VH, Morales ME, Kalinna BH, Brindley PJ | title = The Sinbad retrotransposon from the genome of the human blood fluke, Schistosoma mansoni, and the distribution of related Pao-like elements | journal =  BMC Evolutionary Biology| volume = 5 | issue = 1 | pages = 20 | date = February 2005 | pmid = 15725362 | pmc = 554778 | doi = 10.1186/1471-2148-5-20 | doi-access = free }}</ref><ref name="wicker">{{cite journal | vauthors = Wicker T, Sabot F, Hua-Van A, Bennetzen JL, Capy P, Chalhoub B, Flavell A, Leroy P, Morgante M, Panaud O, Paux E, SanMiguel P, Schulman AH | s2cid = 32132898 | title = A unified classification system for eukaryotic transposable elements | journal = Nature Reviews. Genetics | volume = 8 | issue = 12 | pages = 973–82 | date = December 2007 | pmid = 17984973 | doi = 10.1038/nrg2165 }}</ref> They encode glycoproteins on the retrovirus envelope needed for entry into the host cell. Retroviruses can move between cells whereas LTR retrotransposons can only move themselves into the genome of the same cell.<ref name="LTR retrotransposon diversity">{{Cite journal|vauthors= Havecker ER, Gao X, Voytas DF|title=The diversity of LTR retrotransposons |journal= Genome Biology|volume = 5 | issue = 225| date = 18 May 2004 |page=225 |doi= 10.1186/gb-2004-5-6-225|pmid=15186483 |pmc=463057 |doi-access=free }}</ref> Many vertebrate genes were formed from retroviruses and LTR retrotransposons. One endogenous retrovirus or LTR retrotransposon has the same function and genomic locations in different species, suggesting their role in evolution.<ref name="vertebrate new genes">{{Cite journal|vauthors= Naville M, Warren IA, Haftek-Terreau Z, Chalopin D, Brunet F, Levin P, Galiana D, Volff JN|title= Not so bad after all: retroviruses and long terminal repeat retrotransposons as a source of new genes in vertebrates |journal= Clinical Microbiology and Infection|volume = 22 | issue = 4|pages= 312–323|date= 17 February 2016|doi= 10.1016/j.cmi.2016.02.001|pmid= 26899828 |doi-access= free}}</ref>
-====Ty1-''copia'' retrotransposons====
+==Non-LTR retrotransposons==
+Like LTR retrotransposons, non-LTR retrotransposons contain genes for reverse transcriptase, RNA-binding protein,  nuclease,  and sometimes ribonuclease H domain<ref>{{cite journal | vauthors = Yadav VP, Mandal PK, Rao DN, Bhattacharya S | title = Characterization of the restriction enzyme-like endonuclease encoded by the Entamoeba histolytica non-long terminal repeat retrotransposon EhLINE1 | journal = The FEBS Journal | volume = 276 | issue = 23 | pages = 7070–82 | date = December 2009 | pmid = 19878305 | doi = 10.1111/j.1742-4658.2009.07419.x | s2cid = 30791213 }}</ref> but they lack the long terminal repeats. RNA-binding proteins bind the RNA-transposition intermediate and nucleases are enzymes that break phosphodiester bonds between nucleotides in nucleic acids. Instead of LTRs, non-LTR retrotransposons have short repeats that can have an inverted order of bases next to each other aside from [[direct repeat]]s found in LTR retrotransposons that is just one sequence of bases repeating itself.
+Although they are retrotransposons, they cannot carry out reverse transcription using an RNA transposition intermediate in the same way as LTR retrotransposons. Those two key components of the retrotransposon are still necessary but the way they are incorporated into the chemical reactions is different. This is because unlike LTR retrotransposons, non-LTR retrotransposons do not contain sequences that bind tRNA.
-Ty1-''copia'' retrotransposons are abundant in species ranging from single-cell [[algae]] to [[bryophytes]], [[gymnosperms]], and [[angiosperms]]. They encode four protein domains in the following order: [[protease]], [[integrase]], [[reverse transcriptase]], and [[ribonuclease H]].
+They mostly fall into two types – LINEs (Long interspersed nuclear elements) and SINEs (Short interspersed nuclear elements). SVA elements are the exception between the two as they share similarities with both LINEs and SINEs, containing Alu elements and different numbers of the same repeat. SVAs are shorter than LINEs but longer than SINEs.
-At least two classification systems exist for the subdivision of Ty1-''copia'' retrotransposons into five lineages:<ref>{{cite journal|last1=Wicker|first1=T|last2=Keller|first2=B|title=Genome-wide comparative analysis of copia retrotransposons in Triticeae, rice, and Arabidopsis reveals conserved ancient evolutionary lineages and distinct dynamics of individual copia families.|journal=Genome Research|date=July 2007|volume=17|issue=7|pages=1072–81|pmid=17556529|doi=10.1101/gr.6214107|pmc=1899118}}</ref><ref>{{cite journal|last1=Llorens|first1=C|last2=Muñoz-Pomer|first2=A|last3=Bernad|first3=L|last4=Botella|first4=H|last5=Moya|first5=A|title=Network dynamics of eukaryotic LTR retroelements beyond phylogenetic trees.|journal=Biology Direct|date=2 November 2009|volume=4|pages=41|pmid=19883502|doi=10.1186/1745-6150-4-41|pmc=2774666}}</ref> ''Sireviruses''/Maximus, Oryco/Ivana, Retrofit/Ale, TORK (subdivided in Angela/Sto, TAR/Fourf, GMR/Tork), and Bianca.
+While historically viewed as "junk DNA", research suggests in some cases, both LINEs and SINEs were incorporated into novel genes to form new functions.<ref name="Santangelo">{{cite journal | vauthors = Santangelo AM, de Souza FS, Franchini LF, Bumaschny VF, Low MJ, Rubinstein M | title = Ancient exaptation of a CORE-SINE retroposon into a highly conserved mammalian neuronal enhancer of the proopiomelanocortin gene | journal = PLOS Genetics | volume = 3 | issue = 10 | pages = 1813–26 | date = October 2007 | pmid = 17922573 | pmc = 2000970 | doi = 10.1371/journal.pgen.0030166 | doi-access = free }}</ref>
-''Sireviruses''/Maximus retrotransposons contain an additional putative envelope gene. This lineage is named for the founder element SIRE1 in the ''[[Soybean|Glycine max]]'' genome,<ref>{{cite journal|last1=Laten|first1=HM|last2=Majumdar|first2=A|last3=Gaucher|first3=EA|title=SIRE-1, a copia/Ty1-like retroelement from soybean, encodes a retroviral envelope-like protein.|journal=Proceedings of the National Academy of Sciences of the United States of America|date=9 June 1998|volume=95|issue=12|pages=6897–902|pmid=9618510|doi=10.1073/pnas.95.12.6897|pmc=22677}}</ref> and was later described in many species such as ''[[Maize|Zea mays]]'',<ref>{{cite journal|last1=Bousios|first1=A|last2=Kourmpetis|first2=YA|last3=Pavlidis|first3=P|last4=Minga|first4=E|last5=Tsaftaris|first5=A|last6=Darzentas|first6=N|title=The turbulent life of Sirevirus retrotransposons and the evolution of the maize genome: more than ten thousand elements tell the story.|journal=The Plant journal|date=February 2012|volume=69|issue=3|pages=475–88|pmid=21967390|doi=10.1111/j.1365-313x.2011.04806.x}}</ref> ''[[Arabidopsis thaliana]]'',<ref>{{cite journal|last1=Kapitonov|first1=VV|last2=Jurka|first2=J|title=Molecular paleontology of transposable elements from Arabidopsis thaliana.|journal=Genetica|date=1999|volume=107|issue=1–3|pages=27–37|pmid=10952195}}</ref> ''[[Beta vulgaris]]'',<ref>{{cite journal|last1=Weber|first1=B|last2=Wenke|first2=T|last3=Frömmel|first3=U|last4=Schmidt|first4=T|last5=Heitkam|first5=T|title=The Ty1-copia families SALIRE and Cotzilla populating the Beta vulgaris genome show remarkable differences in abundance, chromosomal distribution, and age.|journal=Chromosome Research|date=February 2010|volume=18|issue=2|pages=247–63|pmid=20039119|doi=10.1007/s10577-009-9104-4}}</ref> and ''[[Pinus pinaster]]''.<ref>{{cite journal|last1=Miguel|first1=C|last2=Simões|first2=M|last3=Oliveira|first3=MM|last4=Rocheta|first4=M|title=Envelope-like retrotransposons in the plant kingdom: evidence of their presence in gymnosperms (Pinus pinaster).|journal=Journal of Molecular Evolution|date=November 2008|volume=67|issue=5|pages=517–25|pmid=18925379|doi=10.1007/s00239-008-9168-3}}</ref> Plant ''Sireviruses'' of many sequenced plant genomes are summarized at the MASIVEdb ''Sirevirus'' database.<ref>{{cite journal|last1=Bousios|first1=A|last2=Minga|first2=E|last3=Kalitsou|first3=N|last4=Pantermali|first4=M|last5=Tsaballa|first5=A|last6=Darzentas|first6=N|title=MASiVEdb: the Sirevirus Plant Retrotransposon Database.|journal=BMC Genomics|date=30 April 2012|volume=13|pages=158|pmid=22545773|doi=10.1186/1471-2164-13-158|pmc=3414828}}</ref>
+===LINEs===
-====Ty3-''gypsy'' retrotransposons====
+{{Main article | Long interspersed nuclear element}}
+When a LINE is transcribed, the transcript contains an RNA polymerase II promoter that ensures LINEs can be copied into whichever location it inserts itself into.  RNA polymerase II is the enzyme that transcribes genes into mRNA transcripts. The ends of LINE transcripts are rich in multiple adenines,<ref name="Liang2013">{{cite journal | vauthors = Liang KH, Yeh CT | title = A gene expression restriction network mediated by sense and antisense Alu sequences located on protein-coding messenger RNAs | journal = BMC Genomics| volume = 14 | pages = 325 | date = May 2013 | pmid = 23663499 | pmc = 3655826 | doi = 10.1186/1471-2164-14-325 | doi-access = free }}</ref> the bases that are added at the end of transcription so that LINE transcripts would not be degraded. This transcript is the RNA transposition intermediate.
-Ty3-''gypsy'' retrotransposons (''Metaviridae'') are widely distributed in the plant kingdom, including both [[gymnosperm]]s and [[Flowering plant|angiosperms]]. They encode at least four protein domains in the order: [[protease]], [[reverse transcriptase]], [[ribonuclease H]], and [[integrase]]. Based on structure, presence/absence of specific protein domains, and conserved protein sequence motifs, they can be subdivided into several lineages:
+The RNA transposition intermediate moves from the nucleus into the cytoplasm for translation. This gives the two coding regions of a LINE that in turn binds back to the RNA it is transcribed from. The LINE RNA then moves back into the nucleus to insert into the eukaryotic genome.
-''Errantiviruses'' contain an additional defective envelope ORF with similarities to the retroviral envelope gene. First described as Athila-elements in ''[[Arabidopsis thaliana]]'',<ref>{{cite journal|last1=Pélissier|first1=T|last2=Tutois|first2=S|last3=Deragon|first3=JM|last4=Tourmente|first4=S|last5=Genestier|first5=S|last6=Picard|first6=G|title=Athila, a new retroelement from Arabidopsis thaliana.|journal=Plant Molecular Biology|date=November 1995|volume=29|issue=3|pages=441–52|pmid=8534844|doi=10.1007/bf00020976}}</ref><ref>{{cite journal|last1=Wright|first1=DA|last2=Voytas|first2=DF|title=Potential retroviruses in plants: Tat1 is related to a group of Arabidopsis thaliana Ty3/gypsy retrotransposons that encode envelope-like proteins.|journal=Genetics|date=June 1998|volume=149|issue=2|pages=703–15|pmid=9611185|pmc=1460185}}</ref> they have been later identified in many species, such as ''[[Soybean|Glycine max]]''<ref>{{cite journal|last1=Wright|first1=DA|last2=Voytas|first2=DF|title=Athila4 of Arabidopsis and Calypso of soybean define a lineage of endogenous plant retroviruses.|journal=Genome Research|date=January 2002|volume=12|issue=1|pages=122–31|pmid=11779837|doi=10.1101/gr.196001|pmc=155253}}</ref> and ''[[Beta vulgaris]]''.<ref>{{cite journal|last1=Wollrab|first1=C|last2=Heitkam|first2=T|last3=Holtgräwe|first3=D|last4=Weisshaar|first4=B|last5=Minoche|first5=AE|last6=Dohm|first6=JC|last7=Himmelbauer|first7=H|last8=Schmidt|first8=T|title=Evolutionary reshuffling in the Errantivirus lineage Elbe within the Beta vulgaris genome.|journal=The Plant Journal|date=November 2012|volume=72|issue=4|pages=636–51|pmid=22804913|doi=10.1111/j.1365-313x.2012.05107.x}}</ref>
+LINEs insert themselves into regions of the eukaryotic genome that are rich in bases AT. At AT regions LINE uses its nuclease to cut one strand of the eukaryotic double-stranded DNA. The adenine-rich sequence in LINE transcript base pairs with the cut strand to flag where the LINE will be inserted with hydroxyl groups. Reverse transcriptase recognises these hydroxyl groups to synthesise LINE retrotransposon where the DNA is cut. Like with LTR retrotransposons, this new inserted LINE contains eukaryotic genome information so it can be copied and pasted into other genomic regions easily. The information sequences are longer and more variable than those in LTR retrotransposons.
-''Chromoviruses'' contain an additional chromodomain (<u>chr</u>omatin <u>o</u>rganization <u>mo</u>difier domain) at the C-terminus of their integrase protein.<ref>{{cite journal|last1=Marín|first1=I|last2=Lloréns|first2=C|title=Ty3/Gypsy retrotransposons: description of new Arabidopsis thaliana elements and evolutionary perspectives derived from comparative genomic data.|journal=Molecular Biology and Evolution|date=July 2000|volume=17|issue=7|pages=1040–9|pmid=10889217|doi=10.1093/oxfordjournals.molbev.a026385}}</ref><ref>{{cite journal|last1=Gorinsek|first1=B|last2=Gubensek|first2=F|last3=Kordis|first3=D|title=Evolutionary genomics of chromoviruses in eukaryotes.|journal=Molecular Biology and Evolution|date=May 2004|volume=21|issue=5|pages=781–98|pmid=14739248|doi=10.1093/molbev/msh057}}</ref> They are widespread in plants and fungi, probably retaining protein domains during evolution of these two kingdoms.<ref>{{cite journal|last1=Novikova|first1=O|last2=Smyshlyaev|first2=G|last3=Blinov|first3=A|title=Evolutionary genomics revealed interkingdom distribution of Tcn1-like chromodomain-containing Gypsy LTR retrotransposons among fungi and plants.|journal=BMC Genomics|date=8 April 2010|volume=11|pages=231|pmid=20377908|doi=10.1186/1471-2164-11-231|pmc=2864245}}</ref> It is thought that the chromodomain directs retrotransposon integration to specific target sites.<ref>{{cite journal|last1=Gao|first1=X|last2=Hou|first2=Y|last3=Ebina|first3=H|last4=Levin|first4=HL|last5=Voytas|first5=DF|title=Chromodomains direct integration of retrotransposons to heterochromatin.|journal=Genome Research|date=March 2008|volume=18|issue=3|pages=359–69|pmid=18256242|doi=10.1101/gr.7146408|pmc=2259100}}</ref> According to sequence and structure of the chromodomain, chromoviruses are subdivided into the four clades CRM, Tekay, Reina and Galadriel. Chromoviruses from each clade show distinctive integration patterns, e.g. into centromeres or into the rRNA genes.<ref>{{cite journal|last1=Neumann|first1=P|last2=Navrátilová|first2=A|last3=Koblížková|first3=A|last4=Kejnovský|first4=E|last5=Hřibová|first5=E|last6=Hobza|first6=R|last7=Widmer|first7=A|last8=Doležel|first8=J|last9=Macas|first9=J|title=Plant centromeric retrotransposons: a structural and cytogenetic perspective.|journal=Mobile DNA|date=3 March 2011|volume=2|issue=1|pages=4|pmid=21371312|doi=10.1186/1759-8753-2-4|pmc=3059260}}</ref><ref>{{cite journal|last1=Weber|first1=B|last2=Heitkam|first2=T|last3=Holtgräwe|first3=D|last4=Weisshaar|first4=B|last5=Minoche|first5=AE|last6=Dohm|first6=JC|last7=Himmelbauer|first7=H|last8=Schmidt|first8=T|title=Highly diverse chromoviruses of Beta vulgaris are classified by chromodomains and chromosomal integration.|journal=Mobile DNA|date=1 March 2013|volume=4|issue=1|pages=8|pmid=23448600|doi=10.1186/1759-8753-4-8|pmc=3605345}}</ref>
+Most LINE copies have variable length at the start because reverse transcription usually stops before DNA synthesis is complete. In some cases this causes RNA polymerase II promoter to be lost so LINEs cannot transpose further.<ref name=Singer>{{cite journal | vauthors = Singer MF | s2cid = 22129236 | title = SINEs and LINEs: highly repeated short and long interspersed sequences in mammalian genomes | journal = Cell | volume = 28 | issue = 3 | pages = 433–4 | date = March 1982 | pmid = 6280868 | doi = 10.1016/0092-8674(82)90194-5 }}</ref>
-Ogre-elements are gigantic Ty3-''gypsy'' retrotransposons reaching lengths up to 25 kb.<ref>{{cite journal|last1=Macas|first1=J|last2=Neumann|first2=P|title=Ogre elements--a distinct group of plant Ty3/gypsy-like retrotransposons.|journal=Gene|date=1 April 2007|volume=390|issue=1–2|pages=108–16|pmid=17052864|doi=10.1016/j.gene.2006.08.007}}</ref>  Ogre elements have been first described in ''[[Pea|Pisum sativum]]''.<ref>{{cite journal|last1=Neumann|first1=P|last2=Pozárková|first2=D|last3=Macas|first3=J|title=Highly abundant pea LTR retrotransposon Ogre is constitutively transcribed and partially spliced.|journal=Plant Molecular Biology|date=October 2003|volume=53|issue=3|pages=399–410|pmid=14750527|doi=10.1023/b:plan.0000006945.77043.ce}}</ref>
+[[File:LINE1s and SINEs.png|thumb|400x400px|Genetic structure of murine LINE1 and SINEs. Bottom: proposed structure of L1 RNA-protein (RNP) complexes. ORF1 proteins form trimers, exhibiting RNA binding and nucleic acid chaperone activity.<ref name=":0">{{Cite journal|title=Transposon regulation upon dynamic loss of DNA methylation (PDF Download Available)|journal=ResearchGate|language=en|doi=10.13140/rg.2.2.18747.21286| vauthors = Walter M |year=2015}}</ref>]]
+====Human L1====
-''Metaviruses'' describe conventional Ty3-''gypsy'' retrotransposons that do not contain additional domains or ORFs.
+{{Main article | LINE1}}
+LINE-1 (L1) retrotransposons make up a significant portion of the human genome, with an estimated 500,000 copies per genome. Genes encoding for human LINE1 usually have their transcription inhibited by methyl groups binding to its DNA carried out by PIWI proteins and enzymes DNA methyltransferases. L1 retrotransposition can disrupt the nature of genes transcribed by pasting themselves inside or near genes which could in turn lead to human disease. LINE1s can only retrotranspose in some cases to form different chromosome structures contributing to differences in genetics between individuals.<ref>{{cite journal | vauthors = Chueh AC, Northrop EL, Brettingham-Moore KH, Choo KH, Wong LH | title = LINE retrotransposon RNA is an essential structural and functional epigenetic component of a core neocentromeric chromatin | journal = PLOS Genetics | volume = 5 | issue = 1 | pages = e1000354 | date = January 2009 | pmid = 19180186 | pmc = 2625447 | doi = 10.1371/journal.pgen.1000354 | veditors = Bickmore WA | doi-access = free }}</ref> There is an estimate of 80–100 active L1s in the reference genome of the Human Genome Project, and an even smaller number of L1s within those active L1s retrotranspose often. L1 insertions have been associated with [[tumorigenesis]] by activating cancer-related genes oncogenes and diminishing tumor suppressor genes.
+Each human LINE1 contains two regions from which gene products can be encoded. The first coding region contains a leucine zipper protein involved in protein-protein interactions and a protein that binds to the terminus of nucleic acids. The second coding region has a purine/pyrimidine nuclease, reverse transcriptase and protein rich in amino acids cysteines and histidines. The end of the human LINE1, as with other retrotransposons is adenine-rich.<ref name="pmid20949108">{{cite journal | vauthors = Doucet AJ, Hulme AE, Sahinovic E, Kulpa DA, Moldovan JB, Kopera HC, Athanikar JN, Hasnaoui M, Bucheton A, Moran JV, Gilbert N | title = Characterization of LINE-1 ribonucleoprotein particles | journal = PLOS Genetics | volume = 6 | issue = 10 | pages = e1001150 | date = October 2010 | pmid = 20949108 | pmc = 2951350 | doi = 10.1371/journal.pgen.1001150 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Denli AM, Narvaiza I, Kerman BE, Pena M, Benner C, Marchetto MC, Diedrich JK, Aslanian A, Ma J, Moresco JJ, Moore L, Hunter T, Saghatelian A, Gage FH | s2cid = 10525450 | title = Primate-specific ORF0 contributes to retrotransposon-mediated diversity | journal = Cell | volume = 163 | issue = 3 | pages = 583–93 | date = October 2015 | pmid = 26496605 | doi = 10.1016/j.cell.2015.09.025 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ohshima K, Okada N | s2cid = 42841487 | title = SINEs and LINEs: symbionts of eukaryotic genomes with a common tail | journal = Cytogenetic and Genome Research | volume = 110 | issue = 1–4 | pages = 475–90 | year = 2005 | pmid = 16093701 | doi = 10.1159/000084981 }}</ref>
-====Endogenous retroviruses (ERV)====
-{{Main article | Endogenous retrovirus}}
-Endogenous retroviruses are the most important LTR retrotransposons in mammals, including humans where the Human ERVs make up 8% of the genome.
+Human L1 actively retrotransposes in the human genome. A recent study identified 1,708 somatic L1 retrotransposition events, especially in colorectal epithelial cells. These events occur from early embryogenesis and retrotransposition rate is substantially increased during colorectal tumourigenesis.<ref>{{Cite journal |last1=Nam |first1=Chang Hyun |last2=Youk |first2=Jeonghwan |last3=Kim |first3=Jeong Yeon |last4=Lim |first4=Joonoh |last5=Park |first5=Jung Woo |last6=Oh |first6=Soo A |last7=Lee |first7=Hyun Jung |last8=Park |first8=Ji Won |last9=Won |first9=Hyein |last10=Lee |first10=Yunah |last11=Jeong |first11=Seung-Yong |last12=Lee |first12=Dong-Sung |last13=Oh |first13=Ji Won |last14=Han |first14=Jinju |last15=Lee |first15=Junehawk |date=2023-05-18 |title=Widespread somatic L1 retrotransposition in normal colorectal epithelium |journal=Nature |language=en |volume=617 |issue=7961 |pages=540–547 |doi=10.1038/s41586-023-06046-z |pmid=37165195 |pmc=10191854 |bibcode=2023Natur.617..540N |issn=0028-0836|doi-access=free }}</ref>
-===Non-LTR retrotransposons===
-Non-LTR retrotransposons consist of two sub-types, long interspersed elements (LINEs) and short interspersed elements (SINEs). They can also be found in high copy numbers, as shown in the plant species.<ref>{{Cite journal|title = LINEs, SINEs and repetitive DNA: non-LTR retrotransposons in plant genomes|url = http://link.springer.com/article/10.1023/A%3A1006212929794|journal = Plant Molecular Biology|date = 1999-08-01|issn = 0167-4412|pages = 903–910|volume = 40|issue = 6|doi = 10.1023/A:1006212929794|first = Thomas|last = Schmidt}}</ref> Non-long terminal repeat (LTR) retroposons are widespread in eukaryotic genomes. LINEs possess two [[Open reading frame|ORF]]s, which encode all the functions needed for retrotransposition. These functions include reverse transcriptase and endonuclease activities, in addition to a nucleic acid-binding property needed to form a ribonucleoprotein particle.<ref>{{cite journal|last=Yadav|first=VP |author2=Mandal, PK |author3=Rao, DN |author4=Bhattacharya, S|title=Characterization of the restriction enzyme-like endonuclease encoded by the Entamoeba histolytica non-long terminal repeat retroposon EhLINE1|journal=The FEBS Journal|date=December 2009|volume=276|issue=23|pages=7070–82|pmid=19878305|doi=10.1111/j.1742-4658.2009.07419.x}}</ref> SINEs, on the other hand, co-opt the LINE machinery and function as nonautonomous retroelements. While historically viewed as "junk DNA", recent research suggests that, in some rare cases, both LINEs and SINEs were incorporated into novel genes so as to evolve new functionality.<ref name="Santangelo">{{cite journal |vauthors=Santangelo AM, de Souza FS, Franchini LF, Bumaschny VF, Low MJ, Rubinstein M |title = Ancient Exaptation of a CORE-SINE Retroposon into a Highly Conserved Mammalian Neuronal Enhancer of the Proopiomelanocortin Gene| journal = PLoS Genetics | volume =3 | issue = 10|publisher = Public Library of Science| date = October 2007 |pmid = 17922573|url = http://genetics.plosjournals.org/perlserv/?request=get-document&doi=10.1371%2Fjournal.pgen.0030166 |pmc = 2000970 | doi = 10.1371/journal.pgen.0030166 | accessdate = 2007-12-31 |pages = 1813–26}}</ref><ref name="Liang2013">{{cite journal |last = Liang| first = Kung-Hao |author2=Yeh, Chau-Ting|title = A gene expression restriction network mediated by sense and antisense Alu sequences located on protein-coding messenger RNAs.| journal = BMC Genomics |pmid = 23663499|url = http://www.biomedcentral.com/1471-2164/14/325 |pmc = 3655826 | doi = 10.1186/1471-2164-14-325 | accessdate = 2013-05-11 | volume=14 | year=2013 | pages=325}}</ref>
-====LINEs====
+===SINEs===
-{{Main article | Long interspersed nuclear element}}
+{{Main article |Short interspersed nuclear element}}
+<!-- see Talk page for explanation why not "Short Interspersed Nuclear Elements" -->
-'''Long INterspersed Elements'''<ref name=Singer>{{cite journal |author=Singer MF |title=SINEs and LINEs: highly repeated short and long interspersed sequences in mammalian genomes |journal=Cell |volume=28 |issue=3 |pages=433–4 |date=March 1982 |pmid=6280868 |url=http://linkinghub.elsevier.com/retrieve/pii/0092-8674(82)90194-5 |doi=10.1016/0092-8674(82)90194-5}}</ref> ('''LINE''') are a group of genetic elements that are found in large numbers in eukaryotic genomes, comprising 17% of the human genome (99.9% of which is no longer capable of retrotransposition, and therefore considered "dead" or inactive).<ref name="pmid20949108">{{cite journal |vauthors=Doucet AJ, Hulme AE, Sahinovic E, Kulpa DA, Moldovan JB, Kopera HC, Athanikar JN, Hasnaoui M, Bucheton A, Moran JV, Gilbert N | title=Characterization of LINE-1 ribonucleoprotein particles | journal=[[PLOS Genetics]]  | volume=6 | issue=10 | date=October 7, 2010 | pages=e1001150  | url = http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1001150 | doi = 10.1371/journal.pgen.1001150 | pmc = 2951350 | id= | pmid=20949108}}</ref> Among the LINE, there are several subgroups, such as L1, L2 and L3. Human coding&nbsp;L1 begin with an untranslated region&nbsp;(UTR) that includes an [[RNA polymerase II]] promoter, two non-overlapping [[open reading frame]]s (ORF1 and ORF2), and ends with another UTR.<ref name="pmid20949108" /> Recently, a new open reading frame in the 5' end of the LINE elements has been identified in the reverse strand. It is shown to be transcribed and endogenous proteins are observed. The name ORF0 is coined due to its position with respect to ORF1 and ORF2.<ref>{{cite journal|last1=Denli|first1=AM|last2=Narvaiza|first2=I|last3=Kerman|first3=BE|last4=Pena|first4=M|last5=Benner|first5=C|last6=Marchetto|first6=MC|last7=Diedrich|first7=JK|last8=Aslanian|first8=A|last9=Ma|first9=J|last10=Moresco|first10=JJ|last11=Moore|first11=L|last12=Hunter|first12=T|last13=Saghatelian|first13=A|last14=Gage|first14=FH|title=Primate-Specific ORF0 Contributes to Retrotransposon-Mediated Diversity.|journal=Cell|date=22 October 2015|volume=163|issue=3|pages=583–93|pmid=26496605|doi=10.1016/j.cell.2015.09.025}}</ref>  ORF1 encodes an RNA binding protein and ORF2 encodes a protein having an [[endonuclease]] (e.g. [[RNase H]]) as well as a [[reverse transcriptase]]. The reverse transcriptase has a higher specificity for the LINE RNA than other RNA, and makes a DNA copy of the RNA that can be integrated into the genome at a new site.<ref>{{cite journal |vauthors=Ohshima K, Okada N |title=SINEs and LINEs: symbionts of eukaryotic genomes with a common tail |journal=Cytogenet. Genome Res. |volume=110 |issue=1–4 |pages=475–90 |year=2005 |pmid=16093701 |doi=10.1159/000084981}}</ref> The endonuclease encoded by non-LTR retroposons may be AP (Apurinic/Pyrimidinic) type or REL (Restriction Endonuclease Like) type. Elements in the R2 group have REL type endonuclease, which shows site specificity in insertion.<ref>{{cite journal|last=Yadav|first=VP |author2=Mandal, PK |author3=Rao, DN |author4=Bhattacharya, S|title=Characterization of the restriction enzyme-like endonuclease encoded by the Entamoeba histolytica non-long terminal repeat retrotransposon EhLINE1|journal=The FEBS Journal|date=December 2009|volume=276|issue=23|pages=7070–82|pmid=19878305|doi=10.1111/j.1742-4658.2009.07419.x}}</ref>
+SINEs are much shorter (300bp) than LINEs.<ref name="Dictionary">{{cite book|title=A dictionary of genetics| vauthors = Stansfield WD, King RC |publisher=Oxford University Press|year=1997|isbn=978-0-19-509441-1|edition=5th|location=Oxford [Oxfordshire]}}</ref> They share similarity with genes transcribed by RNA polymerase II, the enzyme that transcribes genes into mRNA transcripts, and the initiation sequence of RNA polymerase III, the enzyme that transcribes genes into ribosomal RNA, tRNA and other small RNA molecules.<ref>{{cite book | vauthors = Kramerov DA, Vassetzky NS | title = Short retroposons in eukaryotic genomes | series = International Review of Cytology | volume = 247 | pages = 165–221 | year = 2005 | pmid = 16344113 | doi = 10.1016/s0074-7696(05)47004-7 }}</ref> SINEs such as mammalian MIR elements have tRNA gene at the start and adenine-rich at the end like in LINEs.
+SINEs do not encode a functional reverse transcriptase protein and rely on other mobile transposons, especially [[Long interspersed nuclear element|LINEs]].<ref>{{cite journal | vauthors = Dewannieux M, Esnault C, Heidmann T | s2cid = 32151696 | title = LINE-mediated retrotransposition of marked Alu sequences | journal = Nature Genetics | volume = 35 | issue = 1 | pages = 41–8 | date = September 2003 | pmid = 12897783 | doi = 10.1038/ng1223 }}</ref> SINEs exploit LINE transposition components despite LINE-binding proteins prefer binding to LINE RNA. SINEs cannot transpose by themselves because they cannot encode SINE transcripts. They usually consist of parts derived from tRNA and LINEs. The tRNA portion contains an RNA polymerase III promoter which the same kind of enzyme as RNA polymerase II. This makes sure the LINE copies would be transcribed into RNA for further transposition. The LINE component remains so LINE-binding proteins can recognise the LINE part of the SINE.
+====Alu elements====
+{{Main article |Alu element}}
+[[Alu element|''Alu'']]s are the most common SINE in primates. They are approximately 350 base pairs long, do not encode proteins and can be recognized by the [[restriction enzyme]] [[List of restriction enzyme cutting sites: A#Whole list navigation|AluI]] (hence the name). Their distribution may be important in some genetic diseases and cancers. Copy and pasting Alu RNA requires the Alu's adenine-rich end and the rest of the sequence bound to a signal. The signal-bound Alu can then associate with ribosomes. LINE RNA associates on the same ribosomes as the Alu. Binding to the same ribosome allows Alus of SINEs to interact with LINE. This simultaneous translation of Alu element and LINE allows SINE copy and pasting.
+===SVA elements===
+SVA elements are present at lower levels than SINES and LINEs in humans. The starts of SVA and Alu elements are similar, followed by repeats and an end similar to endogenous retrovirus. LINEs bind to sites flanking SVA elements to transpose them. SVA are one of the youngest transposons in great apes genome and among the most active and polymorphic in the human population. SVA was created by a fusion between an Alu element, a VNTR (variable number tandem repeat), and an LTR fragment.<ref name="pmid32955944">{{cite journal |last1=Wells |first1=JN |last2=Feschotte |first2=C |title=A Field Guide to Eukaryotic Transposable Elements. |journal=Annual Review of Genetics |date=23 November 2020 |volume=54 |pages=539–561 |doi=10.1146/annurev-genet-040620-022145 |pmid=32955944 |pmc=8293684}}</ref>
+==Role in human disease==
+Retrotransposons ensure they are not lost by chance by occurring only in cell genetics that can be passed on from one generation to the next from parent gametes. However, LINEs can transpose into the human embryo cells that eventually develop into the nervous system, raising the question whether this LINE retrotransposition affects brain function. LINE retrotransposition is also a feature of several cancers, but it is unclear whether retrotransposition itself causes cancer instead of just a symptom. Uncontrolled retrotransposition is bad for both the host organism and retrotransposons themselves so they have to be regulated. Retrotransposons are regulated by [[RNA interference]]. RNA interference is carried out by a bunch of short [[non-coding RNA]]s. The short non-coding RNA interacts with protein Argonaute to degrade retrotransposon transcripts and change their DNA histone structure to reduce their transcription.
+==Role in evolution==
+LTR retrotransposons came about later than non-LTR retrotransposons, possibly from an ancestral non-LTR retrotransposon acquiring an integrase from a DNA transposon. Retroviruses gained additional properties to their virus envelopes by taking the relevant genes from other viruses using the power of LTR retrotransposon.
+Due to their retrotransposition mechanism, retrotransposons amplify in number quickly, composing 40% of the human genome. The insertion rates for LINE1, Alu and SVA elements are 1/200 – 1/20, 1/20 and 1/900 respectively. The LINE1 insertion rates have varied a lot over the past 35 million years, so they indicate points in genome evolution.
-The 5' [[Untranslated region|UTR]] contains the promoter sequence, while the 3' UTR contains a polyadenylation signal (AATAAA) and a [[poly-A]] tail.<ref name=Paper>{{cite journal |vauthors=Deininger PL, Batzer MA |title=Mammalian retroelements |journal=Genome Res. |volume=12 |issue=10 |pages=1455–65 |date=October 2002 |pmid=12368238 |doi=10.1101/gr.282402 }}</ref> Because LINEs (and other class I transposons, e.g. LTR retrotransposons and SINEs) move by copying themselves (instead of moving by a cut and paste like mechanism, as class II [[transposons]] do), they enlarge the genome. The human genome, for example, contains about 500,000 LINEs, which is roughly 17% of the genome.<ref name=Cordaux>{{cite journal |author1=Richard Cordaux |author2=Mark Batzer |title=The impact of retrotransposons on human genome evolution |journal=Nature Reviews Genetics |volume=10 |issue=10 |pages=691–703 |date=October 2009 |pmid=19763152 |url=http://www.nature.com/nrg/journal/v10/n10/full/nrg2640.html |pmc=2884099 |doi=10.1038/nrg2640}}</ref> Of these, approximately 7,000 are full-length, a small subset of which are capable of retrotransposition.<ref name=Griffiths>{{cite book |author=Griffiths, Anthony J. |title=Introduction to genetic analysis |publisher=W.H. Freeman |location=New York |year=2008 |page=505 |edition=9th |isbn=0-7167-6887-9 }}</ref><ref>{{cite journal |vauthors=Rangwala S, Kazazian HH |title=Many LINE1 elements contribute to the transcriptome of human somatic cells |journal=Genome Biology |volume=10 |issue=9 |pages=R100 |year=2009 |pmid=19772661 |pmc=2768975 |doi=10.1186/gb-2009-10-9-r100}}</ref>
+Notably a large number of 100 kilobases in the maize genome show variety due to the presence or absence of retrotransposons. However since maize is unusual genetically as compared to other plants it cannot be used to predict retrotransposition in other plants.
-Interestingly, it was recently found that specific LINE-1 retroposons in the human genome are actively transcribed and the associated LINE-1 RNAs are tightly bound to nucleosomes and essential in the establishment of local [[chromatin]] environment.<ref>{{cite journal|last=Chueh|first=A.C.|title=LINE Retrotransposon RNA Is an Essential Structural and Functional Epigenetic Component of a Core Neocentromeric Chromatin|journal=PLoS Genetics|date=Jan 2009|volume=5|issue=1|pages=e1000354|pmid=19180186|doi=10.1371/journal.pgen.1000354|pmc=2625447|editor1-last=Bickmore|editor1-first=Wendy A.|last2=Northrop|first2=Emma L.|last3=Brettingham-Moore|first3=Kate H.|last4=Choo|first4=K. H. Andy|last5=Wong|first5=Lee H.}}</ref>
+Mutations caused by retrotransposons include:
-====SINEs====
+* Gene inactivation
-'''Short INterspersed Elements'''<ref name=Singer/> are short DNA sequences (<500 bases<ref name=Dictionary>{{cite book |author1=Stansfield, William D. |author2=King, Robert C. |title=A dictionary of genetics |publisher=Oxford University Press |location=Oxford [Oxfordshire] |year=1997 |edition=5th |isbn=0-19-509441-7 }}</ref>) that represent reverse-transcribed RNA molecules originally transcribed by [[RNA polymerase III]] into [[transfer RNA]], [[5S ribosomal RNA]], and other small nuclear RNAs. The mechanism of retrotransposition of these elements is more complicated than LINEs, and less dependent solely on the actual elements that they encode. SINEs do not encode a functional reverse transcriptase protein and rely on other mobile elements for transposition. In some cases they may have their own [[endonuclease]] that will allow them to cleave their way into the genome, but the majority of SINEs integrate at chromosomal breaks by using random DNA breaks to prime reverse transcriptase.<ref name=Singer/> With about 1,500,000 copies, SINEs make up about 11% of the human genome.<ref name="Cordaux" />
+* Changing gene regulation
+* Changing gene products
+* Acting as DNA repair sites
+==Role in biotechnology==
-===== ''Alu'' =====
-{{Main article|Alu element}}
+{{Empty section|date=January 2021}}
-The most common SINE in primates is [[Alu element|''Alu'']]. ''Alu'' elements are approximately 350 base pairs long, do not contain any coding sequences, and can be recognized by the [[restriction enzyme]] [[List of restriction enzyme cutting sites: A#Whole list navigation|AluI]] (hence the name). The distribution of these elements has been implicated in some genetic diseases and cancers.<ref>{{cite journal|last1=Chénais|first1=Benoît|title=Transposable elements and human cancer: A causal relationship?|journal=Biochimica et Biophysica Acta (BBA) - Reviews on Cancer|date=January 2013|volume=1835|issue=1|pages=28–35|doi=10.1016/j.bbcan.2012.09.001|pmid=22982062}}</ref>
-==See also==
+== See also ==
+* [[Copy-number variation]]
-*[[Transposon]]
-*[[Endogenous retrovirus]]
+* [[Genomic organization]]
+* [[Insertion sequences]]
-*[[Paleogenetics]]
+* [[Interspersed repeat]]
-*[[Paleovirology]]
+* [[Paleogenetics]]
-*[[Insertion sequences]]
+* [[Paleovirology]]
-*[[Copy-number variation]]
+* [[RetrOryza]]
-*[[Genomic organization]]
+* [[Retrotransposon marker]]s, a powerful method of reconstructing phylogenies.
-*[[Interspersed repeat]]
+* [[Tn3 transposon]]
-*[[Retrotransposon marker]]s, a powerful method of reconstructing phylogenies.
-*[[RetrOryza]]
+* [[Transposon]]
+* [[Retron]]
-==References==
+== References ==
-{{Reflist|2}}
+{{Reflist|30em}}
 {{Repeated sequence}}
+{{Self-replicating organic structures}}
 [[Category:Mobile genetic elements]]
 [[Category:Molecular biology]]
+[[Category:Non-coding DNA]]