Abstract
The human genome contains a large number of repetitive elements derived from transposable elements (TEs). In addition to active Alu and long interspersed element (LINE or L1) interspersed repeats, the human genome comprises a large number of ancient TEs. These include fossil germ-line insertions of DNA transposons, fossil short interspersed elements (SINEs), L2, and L3 LINEs. Processed pseudogenes and human endogenous retroviruses (HERVs) have amplified more recently in evolutionary history and some of them are still well preserved. Copies of some of the recently extinct TEs continue to contribute to genomic rearrangements by homologous recombination. In this chapter, we review ancient SINE and LINE repeats, processed pseudogenes, HERVs, and DNA transposons. We briefly introduce the genomic structure and replication strategy of these elements, their expression competence, and focus on the contribution of these repeats to human diseases. We also discuss some of the TE-derived genes and regulatory elements.
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References
Temin HM, Mizutani S. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 1970;226:1211–1213.
Baltimore D. RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 1970;226: 1209–1211.
International Human Genome Sequencing Consortium. Initial sequencing and analysis of the human genome. Nature 2001;409:860–921.
Jurka J. Repbase update: a database and an electronic journal of repetitive elements. Trends Genet 2000;16:418–420.
Kapitonov VV, Jurka J. The esterase and PHD domains in CR1-like non-LTR retrotransposons. Mol Biol Evol 2003;20:38–46.
Kapitonov VV, Pavlicek A, Jurka J. Anthology of Human Repetitive DNA. In: Encyclopedia of Molecular Cell Biology and Molecular Medicine, vol. 1 (Meyers RA, ed.). Weinheim, Germany: Wiley-VCH 2004; pp 251–306.
Luan DD, Korman MH, Jakubczak JL, Eickbush TH. Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell 1993;72:595–605.
Smit AF, Riggs AD. MIRs are classic, tRNA-derived SINEs that amplified before the mammalian radiation. Nucleic Acids Res 1995;23:98–102.
Okada N, Hamada M, Ogiwara I, Ohshima K. SINEs and LINEs sharecommon3′ sequences: areview. Gene 1997;205:229–243.
Jacq C, Miller JR, Brownlee GG. Apseudogene structure in 5S DNAof Xenopus laevis. Cell 1997;12:109–120.
Vanin EF. Processed pseudogenes: characteristics and evolution. Annu Rev Genet 1985;19:253–272.
Weiner AM, Deininger PL, Efstratiadis A. Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu Rev Biochem 1986;55:631–661.
Jurka J. S equence patterns indicate an enzymatic involvement in integration of mammalian retroposons. Proc Natl Acad Sci USA 1997;94:1872–1877.
Tchenio T, Segal-Bendirdjian E, Heidmann T. Generation of processed pseudogenes in murine cells. EMBO J 1993;12:1487–1497.
Maestre J, Tchenio T, Dhellin O, Heidmann T. mRNA retroposition in human cells: processed pseudogene formation. EMBO J 1995;14:6333–6338.
Dhellin O, Maestre J, Heidmann T. Functional differences between the human LINE retrotransposon and retroviral reverse transcriptases for in vivo mRNA reverse transcription. EMBO J 1997;16:6590–6602.
Esnault C, Maestre J, Heidmann T. Human LINE retrotransposons generate processed pseudogenes. Nat Genet 2000;24:363–367.
Wei W, Gilbert N, Ooi SL, et al. Human L1 retrotransposition: cis preference versus trans complementation. Mol Cell Biol 2001;21:1429–1439.
Ohshima K, Hattori M, Yada T, Gojobori T, Sakaki Y, Okada N. Whole-genome screening indicates a possible burst of formation of processed pseudogenes and Alu repeats by particular L1 subfamilies in ancestral primates. Genome Biol 2003;4:R74.
Zhang Z, Harrison PM, Liu Y, Gerstein M. Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome. Genome Res 2003;13:2541–2558.
Pavlicek A, Jabbari K, Paces J, Paces V, Hejnar J, Bernardi G. Similar integration but different stability of Alus and LINEs in the human genome. Gene 2001;276:39–45.
Zhang Z, Harrison P, Gerstein M. Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome. Genome Res 2002; 12:1466–1482.
Pavlicek A, Paces J, Zika R, Hejnar J. Length distribution of long interspersed nucleotide elements (LINEs) and processed pseudogenes of human endogenous retroviruses: implications for retrotransposition and pseudogene detection. Gene 2002;300:189–194.
Zhang Z, Gerstein M. Identification and characterization of over 100 mitochondrial ribosomal protein pseudogenes in the human genome. Genomics 2003;81:468–480.
Strichman-Almashanu LZ, Bustin M, Landsman D. Retroposed copies of the HMG genes: a window to genome dynamics. Genome Res 2003;13:800–812.
Jamain S, Girondot M, Leroy P, et al. Transduction of the human gene FAM8A1 by endogenous retrovirus during primate evolution. Genomics 2001;78:38–45.
Goncalves I, Duret L, Mouchiroud D. Nature and structure of human genes that generate retropseudogenes. Genome Res 2000; 10:672–678.
Torrents D, Suyama M, Zdobnov E, Bork P. A genome-wide survey of human pseudogenes. Genome Res 2003;13:2559-2567.
Harrison PM, Hegyi H, Balasubramanian S, et al. Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22. Genome Res 2002;12:272–280.
Pavlicek A, Paces J, Elleder D, Hejnar J. Processed pseudogenes of human endogenous retroviruses generated by LINEs: their integration, stability, and distribution. Genome Res 2002;12:391–399.
Ejima Y, Yang L. Trans mobilization of genomic DNA as a mechanism for retrotransposon-mediated exon shuffling. Hum Mol Genet 2003;12:1321–1328.
Goodchild NL, Freeman JD, Mager DL. Spliced HERV-H endogenous retroviral sequences in human genomic DNA: evidence for amplification via retrotransposition. Virology 1995;206:164–173.
Costas J. Characterization of the intragenomic spread of the human endogenous retrovirus family HERV-W. Mol Biol Evol 2002;19:526–533.
Boeke JD. LINEs and Alus: the polyA connection. Nat Genet 1997;16:6–7.
Brosius J. RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements. Gene 1999;238:115–134.
Gentles AJ, Karlin S. Why are human G-protein-coupled receptors predominantly intronless? Trends Genet 1999; 15:47–49.
Harrison PM, Gerstein M. Studying genomes through the aeons: protein families, pseudogenes and proteome evolution. J Mol Biol 2002;318:1155–1174.
McCarrey JR, Kumari M, Aivaliotis MJ, et al. Analysis of the cDNA and encoded protein of the human testis-specific PGK-2 gene. Dev Genet 1996;19:321–332.
Fujii GH, Morimoto AM, Berson AE, Bolen JB. Transcriptional analysis of the PTEN/MMAC1 pseudogene, psiPTEN. Oncogene 1999;18:1765–1769.
Olsen MA, Schechter LE. Cloning, mRNA localization and evolutionary conservation of a human 5-HT7 receptor pseudogene. Gene 1999;227:63–69.
Reyes A, Mezzina M, Gadaleta G. Human mitochondrial transcription factor A (mtTFA): gene structure and characterization of related pseudogenes. Gene 2002;291:223–232.
Yano Y, Saito R, Yoshida N, et al. A new role for expressed pseudogenes as ncRNA: regulation of mRNA stability of its homologous coding gene. J Mol Med 2004;82:414–422.
McCarrey JR, Thomas K. Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene. Nature 1987;326:501–505.
Ashworth A, Skene B, Swift S, Lovell-Badge R. Zfa is an expressed retroposon derived from an alternative transcript of the Zfx gene. EMBO J 1990:9:1529–1534.
Dahl HH, Brown RM, Hutchison WM, Maragos C, Brown GK. A testis-specific form of the human pyruvate dehydrogenase E1 alpha subunit is coded for by an intronless gene on chromosome 4. Genomics 1990;8: 225–232.
Mardon G, Luoh SW, Simpson EM, Gill G, Brown LG, Page DC. Mouse Zfx protein is similar to Zfy-2: each contains an acidic activating domain and 13 zinc fingers. Mol Cell Biol 1990;10:681–688.
Sargent CA, Young C, Marsh S, Ferguson-Smith MA, Affara NA. The glycerol kinase gene family: structure of the Xp gene, and related intronless retroposons. Hum Mol Genet 1994;3:1317–1324.
Hendriksen PJ, Hoogerbrugge JW, Baarends WM, et al. Testis-specific expression of a functional retroposon encoding glucose-6-phosphate dehydrogenase in the mouse. Genomics 1997;41:350–359.
Sedlacek Z, Munstermann E, Dhorne-Pollet S, et al. Human and mouse XAP-5 and XAP-5-like (X5L) genes: identification of an ancient functional retroposon differentially expressed in testis. Genomics 1999;61: 125–132.
Elliott DJ, Venables JP, Newton CS, et al. An evolutionarily conserved germ cell-specific hnRNP is encoded by a retrotransposed gene. Hum Mol Genet 2000;9:2117–2124.
Dass B, McMahon KW, Jenkins NA, Gilbert DJ, Copeland NG, MacDonald CC. The gene for a variant form of the polyadenylation protein CstF-64 is on chromosome 19 and is expressed in pachytene spermatocytes in mice. J Biol Chem 2001;276:8044–8050.
Wang PJ, Page DC. Functional substitution for TAF(II)250 by a retroposed homolog that is expressed in human spermatogenesis. Hum Mol Genet 2002;11:2341–2346.
Emerson JJ, Kaessmann H, Betran E, Long M. Extensive gene traffic on the mammalian X chromosome. Science 2004;303:537–540.
Bradley J, Baltus A, Skaletsky H, Royce-Tolland M, Dewar K, Page DC. An X-to-autosome retrogene is required for spermatogenesis in mice. Nat Genet 2004;36:872–876.
Dupuy D, Duperat VG, Arveiler B. SCAN domain-containing 2 gene (SCAND2) is a novel nuclear protein derived from the zinc finger family by exon shuffling. Gene 2002;289:1–6.
Hirotsune S, Yoshida N, Chen A, et al. An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Nature 2003;423:91–96.
Ostertag EM, Kazazian HH Jr. Biology of mammalian L1 retrotransposons. Annu Rev Genet 2001;35: 501–538.
Scherrer K. Control of gene expression in animal cells: the cascade regulation hypothesis revisited. Adv Exp Med Biol 1974;44:169–219.
Coffin JM, Hughes SH, Varmus HE. Retroviruses. Cold Spring Harbor Laboratory Press, New York, NY, 1997.
Cianciolo GJ, Copeland TD, Oroszlan S, Snyderman R. Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins. Science 1985;230:453–455.
Sonigo P, Barker C, Hunter E, Wain-Hobson S. Nucleotide sequence of Mason-Pfizer monkey virus: an immunosuppressive D-type retrovirus. Cell 1986;45:375–385.
Bukreyev A, Volchkov VE, Blinov VM, Netesov SV. The GP-protein of Marburg virus contains the region similar to the’ immunosuppressive domain’ of oncogenic retrovirus P15E proteins. FEBS Lett 1993;323: 183–187.
Benit L, Lallemand JB, Casella JF, Philippe H, Heidmann T. ERV-L elements: a family of endogenous retrovirus-like elements active throughout the evolution of mammals. J Virol 1999;73:3301–3308.
Yin H, Medstrand P, Kristofferson A, Dietrich U, Aman P, Blomberg J. Characterization of human MMTV-like (HML) elements similar to a sequence that was highly expressed in a human breast cancer: further definition of the HML-6 group. Virology 1999;256:22–35.
Magin C, Lower R, Lower J. cORF and RcRE, the Rev/Rex and RRE/RxRE homologues of the human endogenous retrovirus family HTDV/HERV-K. J Virol 1999;73:9496–9507.
Yang J, Bogerd HP, Peng S, Wiegand H, Truant R, Cullen BR. An ancient family of human endogenous retro viruses encodes a functional homolog of the HIV-1 Rev protein. Proc Natl Acad Sci USA 1999;96:13,404–13,408.
Martin MA, Bryan T, Rasheed S, Khan AS. Identification and cloning of endogenous retroviral sequences present in human DNA. Proc Natl Acad Sci USA 1981;78:4892–4896.
Paces J, Pavlicek A, Zika R, Kapitonov VV, Jurka J, Paces V. HERVd: the Human Endogenous Retro Viruses Database: update. Nucleic Acids Res 2004;32:D50.
Wilkinson DA, Mager DL, Leong JC. Endogenous human retro viruses. In: The Retroviridae (Levy, J. A., ed.). New York, NY: Plenum Press, 1994; pp 465–535.
Zhang J, Temin HM. Rate and mechanism of nonhomologous recombination during a single cycle of retro viral replication. Science 1993;259:234–238.
Cordonnier A, Casella JF, Heidmann T. Isolation of novel human endogenous retro virus-like elements with foamy virus-related pol sequence. J Virol 1995;69:5890–5897.
Charlier C, Segers K, Wagenaar D, et al. Human-ovine comparative sequencing of a 250-kb imprinted domain encompassing the callipyge (clpg) locus and identification of six imprinted transcripts: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8. Genome Res 2001;11:850–862.
Ono R, Kobayashi S, Wagatsuma H, et al. A retrotransposon-derived gene, PEG10, is a novel imprinted gene located on human chromosome 7q21. Genomics 2001;73:232–237.
Lynch C, Tristem M. A co-opted gypsy-type LTR-retrotransposon is conserved in the genomes of humans, sheep, mice, and rats. Curr Biol 2003;13:1518–1523.
Dewannieux M, Dupressoir A, Harper F, Pierron G, Heidmann T. Identification of autonomous IAP LTR retrotransposons mobile in mammalian cells. Nat Genet 2004;36:534–539.
Cohen M, Powers M, O’ Connell C, Kato N. The nucleotide sequence of the env gene from the human provirus ERV3 and isolation and characterization of an ERV3-specific cDNA. Virology 1985;147:449–458.
Blond JL, Beseme F, Duret L, et al. Molecular characterization and placental expression of HERV-W, a new human endogenous retrovirus family. J Virol 1999;73:1175–1185.
Kjellman C, Sjogren HO, Salford LG, Widegren B. HERV-F (XA34) is a full-length human endogenous retrovirus expressed in placental and fetal tissues. Gene 1999;239:99–107.
Lindeskog M, Mager DL, Blomberg J. Isolation of a human endogenous retroviral HERV-H element with an open env reading frame. Virology 1999;258:441–450.
Benit L, Dessen P, Heidmann T. Identification, phylogeny, and evolution of retroviral elements based on their envelope genes. J Virol 2001;75:11,709–11,719.
Mouse Genome Sequencing Consortium. Initial sequencing and comparative analysis of the mouse genome. Nature 2002;420:520–562.
Rat Genome Sequencing Project Consortium. Genome sequence of the Brown Norway rat yields insights into mammalian evolution. Nature 2004;428:493–521.
Medstrand P, Mager DL. Human-specific integrations of the HERV-K endogenous retrovirus family. J Virol 1998;72:9782–9787.
Barbulescu M, Turner G, Seaman MI, Deinard AS, Kidd KK, Lenz J. Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans. Curr Biol 1999;9:861–868.
Mayer J, Sauter M, Racz A, Scherer D, Mueller-Lantzsch N, Meese E. An almost-intact human endogenous retrovirus K on human chromosome 7. Nat Genet 1999;21:257–258.
Turner G, Barbulescu M, Su M, Jensen-Seaman MI, Kidd KK, Lenz J. Insertional polymorphisms of full-length endogenous retroviruses in humans. Curr Biol 2001;11:1531–1535.
Elleder D, Pavlicek A, Paces J, Hejnar J. Preferential integration of human immunodeficiency virus type 1 into genes, cytogenetic R bands and GC-rich DNA regions: insight from the human genome sequence. FEBS Lett 2002;517:285–286.
Schroder AR, Shinn P, Chen H, Berry C, Ecker JR, Bushman F. HIV-1 integration in the human genome favors active genes and local hotspots. Cell 2002; 110:521–529.
Wu X, Li Y, Crise B, Burgess SM. Transcription start regions in the human genome are favored targets for MLV integration. Science 2003;300:1749–1751.
Smit AF. Interspersed repeats and other mementos of transposable elements in mammalian genomes. Curr Opin Genet Dev 1999;9:657–663.
Mager DL, Goodchild NL. Homologous recombination between the LTRs of a human retrovirus-like element causes a 5-kb deletion in two siblings. Am J Hum Genet 1989;45:848–854.
Erlandsson R, Wilson JF, Paabo S. Sex chromosomal transposable element accumulation and male-driven substitutional evolution in humans. Mol Biol Evol 2000;17:804–812.
Medstrand P, van de Lagemaat LN, Mager DL. Retroelement distributions in the human genome: variations associated with age and proximity to genes. Genome Res 2002; 12:1483–1495.
Blanco P, Shlumukova M, Sargent CA, Jobling MA, Affara N, Hurles ME. Divergent outcomes of intrachromosomal recombination on the human Y chromosome: male infertility and recurrent polymorphism. J Med Genet 2000;37:752–758.
Sun C, Skaletsky H, Rozen S, et al. Deletion of azoospermia factor a (AZFa) region of human Y chromosome caused by recombination between HERV15 proviruses. Hum Mol Genet 2000;9:2291–2296.
Kamp C, Hirschmann P, Voss H, Huellen K, Vogt PH. Two long homologous retroviral sequence blocks in proximal Yq 11 cause AZFa microdeletions as a result of intrachromosomal recombination events. Hum Mol Genet 2000;9:2563–2572.
Kamp C, Huellen K, Fernandes S, et al. High deletion frequency of the complete AZFa sequence in men with Sertoli-cell-only syndrome. Mol Hum Reprod 2001;7:987–994.
Kambhu S, Falldorf P, Lee JS. Endogenous retroviral long terminal repeats within the HLA-DQ locus. Proc Natl Acad Sci USA 1990;87:4927–4931.
Kulski JK, Gaudieri S, Martin A, Dawkins RL. Coevolution of PERB11 (MIC) and HLA class I genes with HERV-16 and retroelements by extended genomic duplication. J Mol Evol 1999;49:84–97.
Nakagawa K, Harrison LC. The potential roles of endogenous retroviruses in autoimmunity. Immunol Rev 1996;152:193–236.
Lower R. The pathogenic potential of endogenous retroviruses: facts and fantasies. Trends Microbiol 1999;7:350–356.
Nelson PN, Carnegie PR, Martin J, et al. Demystified. Human endogenous retroviruses. Mol Pathol 2003;56:11–18.
Perl A. Role of endogenous retroviruses in autoimmune diseases. Rheum Dis Clin North Am 2003;29:123–143.
Garson JA, Tuke PW, Giraud P, Paranhos-Baccala G, Perron H. Detection of virion-associated MSRV-RNA in serum of patients with multiple sclerosis. Lancet 1998;351:33.
Poser CM. Virion-associated MSRV-RNA in multiple sclerosis. Lancet 1998;351:755.
Lower R. Response from Lower. Trends Microbiol 1999;7:431–432.
Mager DL. Human endogenous retroviruses and pathogenicity: genomic considerations. Trends Microbiol 1999;7:431.
Stoye JP. The pathogenic potential of endogenous retroviruses: a sceptical view. Trends Microbiol 1999;7:430.
Sverdlov ED. Retroviruses and primate evolution. Bioessays 2000;22:161–171.
Landry JR, Mager DL, Wilhelm BT. Complex controls: the role of alternative promoters in mammalian genomes. Trends Genet 2003;19:640–648.
van de Lagemaat LN, Landry JR, Mager DL, Medstrand P. Transposable elements in mammals promote regulatory variation and diversification of genes with specialized functions. Trends Genet 2003;19:530–536.
Samuelson LC, Wiebauer K, Snow CM, Meisler MH. Retroviral and pseudogene insertion sites reveal the lineage of human salivary and pancreatic amylase genes from a single gene during primate evolution. Mol Cell Biol 1990;10:2513–2520.
Ting CN, Rosenberg MP, Snow CM, Samuelson LC, Meisler MH. Endogenous retroviral sequences are required for tissue-specific expression of a human salivary amylase gene. Genes Dev 1992;6:1457–1465.
Blond JL, Lavillette D, Cheynet V, et al. An envelope glycoprotein of the human endogenous retrovirus HERV-W is expressed in the human placenta and fuses cells expressing the type D mammalian retrovirus receptor. J Virol 2000;74:3321–3329.
Mi S, Lee X, Li X, et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 2000;403:785–789.
Blaise S, de Parseval N, Benit L, Heidmann T. Genomewide screening for fusogenic human endogenous retro virus envelopes identifies syncytin 2, a gene conserved on primate evolution. Proc Natl Acad Sci USA 2003;100:13,013–13,018.
Smit AF, Riggs AD. Tiggers and DNA transposon fossils in the human genome. Proc Natl Acad Sci USA 1996;93:1443–1448.
Reiter LT, Murakami T, Koeuth T, et al. A recombination hotspot responsible for two inherited peripheral neuropathies is located near a mariner transposon-like element. Nat Genet 1996;12:288–297.
Reiter LT, Liehr T, Rautenstrauss B, Robertson HM, Lupski JR. Localization of mariner DNA transposons in the human genome by PRINS. Genome Res 1999;9:839–843.
Kapitonov VV, Jurka J. RAG1 core and V(D)J recombination signal sequences were derived from Transib transposons. PLoS Biol 2005;3:e181.
Kapitonov VV, Jurka J. MER53, a non-autonomous DNA transposon associated with a variety of functionally related defense genes in the human genome. DNA Seq 1998;8:277–288.
Jurka J, Kapitonov VV. Sectorial mutagenesis by transposable elements. Genetica 1999; 107:239–248.
Kapitonov VV, Jurka J. Harbinger transposons and an ancient HARBI1 gene derived from a transposase. DNA Cell Biol 2004;23:311–324.
Lee GS, Neiditch MB, Salus SS, Roth DB. RAG proteins shepherd double-strand breaks to a specific pathway, suppressing error-prone repair, but RAG nicking initiates homologous recombination. Cell 2004;117:171–184.
Raghavan SC, Swanson PC, Wu X, Hsieh CL, Lieber MR. A non-B-DNA structure at the Bcl-2 major breakpoint region is cleaved by the RAG complex. Nature 2004;428:88–93.
Ivics Z, Hackett PB, Plasterk RH, Izsvak Z. Molecular reconstruction of Sleeping Beauty, a Tc1-like transposon from fish, and its transposition in human cells. Cell 1997;91:501–510.
Yant SR, Meuse L, Chiu W, Ivics Z, Izsvak Z, Kay MA. Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system. Nat Genet 2000;25:35–41.
Jurka J. Repeats in genomic DNA: mining and meaning. Curr Opin Struct Biol 1998;8:333–337.
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Pavlicek, A., Jurka, J. (2006). Ancient Transposable Elements, Processed Pseudogenes, and Endogenous Retroviruses. In: Lupski, J.R., Stankiewicz, P. (eds) Genomic Disorders. Humana Press. https://doi.org/10.1007/978-1-59745-039-3_4
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