Journal Mobile Options
Table of Contents
Vol. 110, No. 1-4, 2005
Issue release date: 2005
Cytogenet Genome Res 110:108–116 (2005)

How repeated retroelements format genome function

von Sternberg R. · Shapiro J.A.
aNational Center for Biotechnology Information, National Institutes of Health, Bethesda, MD and Department of Systematic Biology, National Museum of Natural History, Smithsonian Institution, Washington, DC; bDepartment of Biochemistry and Molecular Biology, University of Chicago, Chicago, IL (USA)

Individual Users: Register with Karger Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in


Genomes operate as sophisticated information storage systems. Generic repeated signals in the DNA format expression of coding sequence files and organize additional functions essential for genome replication and accurate transmission to progeny cells. Retroelements comprise a major fraction of many genomes and contain a surprising diversity of functional signals. In this article, we summarize some features of the taxonomic distribution of retroelements, especially mammalian SINEs, tabulate functional roles documented for different classes of retroelements, and discuss their potential roles as genome organizers. In particular, the fact that certain retroelements serve as boundaries for heterochromatin domains and provide a significant fraction of scaffolding/matrix attachment regions (S/MARs) suggests that the reversed transcribed component of the genome plays a major architectonic role in higher order physical structuring. Employing an information science model, the “functionalist” perspective on repetitive DNA leads to new ways of thinking about the systemic organization of cellular genomes and provides several novel possibilities involving retroelements in evolutionarily significant genome reorganization.    

Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.


  1. Allen E, Horvath S, Tong F, Spiteri E, Riggs AD, Marahrens Y: High concentrations of long interspersed nuclear element sequence distinguish monoallelically expressed genes. Proc Natl Acad Sci USA 100:9940–9945 (2003).
  2. Ananiev EV, Phillips RL, Rines HW: Complex structure of knob DNA on maize chromosome 9: retrotransposon invasion into heterochromatin. Genetics 149:2025–2037 (1998a).
  3. Ananiev EV, Phillips RL, Rines HW: Chromosome-specific molecular organization of maize (Zea mays L.) centromeric regions. Proc Natl Acad Sci USA 95:13073–13078 (1998b).
  4. Aragon-Alcaide L, Miller T, Schwarzacher T, Reader S, Moore G: A cereal centromeric sequence. Chromosoma 105:261–268 (1996).
  5. Arkhipova IR, Morrison HG: Three retrotransposon families in the genome of Giardia lamblia: two telomeric, one dead. Proc Natl Acad Sci USA 98:14497–14502 (2001).
  6. Babich V, Aksenov N, Alexeenko V, Oei SL, Buchlow G, Tomilin N: Association of some potential hormone response elements in human genes with Alu family repeats. Gene 239:341–349 (1999).
  7. Bailey JA, Carrel L, Chakravarti A, Eichler EE: Molecular evidence for a relationship between LINE-1 elements and X chromosome inactivation: The Lyon repeat hypothesis. Proc Natl Acad Sci USA 97:6634–6639 (2000).
  8. Bailey JA, Liu G, Eichler EE: An Alu transposition model for the origin and expansion of human segmental duplications. Am J Hum Genet 73:823–834 (2003).
  9. Becker KG, Swergold GD, Ozata K, Thayer RE: Binding of the ubiquitous nuclear transcription factor YY1 to a cis regulatory sequence in the human LINE-1 transposable element. Hum Mol Genet 2:1697–1702 (1993).
  10. Bennett MD: Plant genome values: how much do we know? Proc Natl Acad Sci USA 95:2011–2016 (1998).
  11. Bennetzen JL: Transposable elements contributions to plant gene and genome evolution. Plant Mol Biol 42:251–269 (2000).
  12. Blackburn EH: The end of the (DNA) line. Nat Struct Biol 7:847–850 (2000).
  13. Borodulina OR, Kramerov DA: Short interspersed elements (SINEs) from insectivores. Two classes of mammalian SINEs distinguished by A-rich tail structure. Mammal Genome 12:779–786 (2001).
  14. Britten RJ: DNA sequence insertion and evolutionary variation in gene regulation. Proc Natl Acad Sci USA 93:9374–9377 (1996).
  15. Britten RJ, Davidson EH: Repetitive and non-repetitive DNA sequences and a speculation on the origins of evolutionary novelty. Quart Rev Biol 46:111–138 (1971).
  16. Brosius J: RNAs from all categories generate retrosequences that may be exapted as novel genes or regulatory elements. Gene 238:115–134 (1999).
  17. Byrd K, Corces VG: Visualization of chromatin domains created by the gypsy insulator of Drosophila. J Cell Biol 162:565–574 (2003).
  18. Cavalier-Smith T: The evolution of genome size (John Wiley & Sons Ltd., Chichester 1985).
  19. Chen D, Kunlin J, Kawaguchi K, Nakayama M, Zhou X, Xiong Z, Zhou A, Mao XO, Greenberg DA, Graham SH, Simon RP: Ero1-L, an ischemia-inducible gene from rat brain with homology to global ischemia-induced gene 11 (Giig11), is localized to neuronal dendrites by a dispersed identifier (ID) element-dependent mechanism. J Neurochem 85:670–679 (2003).
  20. Chen S, Corces VG: The gypsy insulator of Drosophila affects chromatin structure in a directional manner. Genetics 159:1649–1658 (2001).
  21. Cheng ZF, Dong T, Langdon S, Ouyang CR, Buell FR, Blattner F, Jiang J: Functional rice centromeres are marked by a satellite repeat and a centromere-specific retrotransposon. Plant Cell 14:1691–1704 (2002).
  22. Cheng Z-J, Murata M: A centromeric tandem repeat family originating from a part of Ty3/gypsy-retroelement in wheat and its relatives. Genetics 164:665–672 (2003).
  23. Chimera JA, Musich PR: The association of the interspersed repetitive KpnI sequences with the nuclear matrix. J Biol Chem 260:9373–9379 (1985).
  24. Chong S, Whitelaw E: Murine metastable alleles and transgenerational epigenetic inheritance. Cytogenet Genome Res 105:311–315 (2004).

    External Resources

  25. Chureau C, Prissette M, Bourdet A, Barbe V, Cattolico L, Jones L, Eggen A, Avner P, Duret L: Comparative sequence analysis of the X-inactivation center region in mouse, human, and bovine. Genome Res 12:894–908 (2002).
  26. Cryderman DE, Cuaycong MH, Elgin SCR, Wallrath LL: Characterization of sequences associated with position-effect variegation at pericentric sites in Drosophila heterochromatin. Chromosoma 107:277–285(1998).
  27. Deininger PL, Moran JV, Batzer MA, Kazazian HH: Mobile elements and mammalian genome evolution. Curr Opin Genet Devel 13:651–658 (2003).
  28. Dimitri P, Junakovic N: Revising the selfish DNA hypothesis: new evidence on accumulation of transposable elements in heterochromatin. Trends Genet 15:123–124 (1999).
  29. Eichler EE: Recent duplication, domain accretion and the dynamic mutation of the human genome. Trends Genet 17:661–669 (2001).
  30. Ferrigno O, Virolle T, Djabari Z, Ortonne JP, White RJ, Aberdam D: Transposable B2 SINE elements can provide mobile RNA polymerase II promoters. Nat Genet 28:77–81 (2001).
  31. Figueiredo LM, Pirrit LA, Scherf A: Genomic organisation and chromatin structure of Plasmodium falciparum chromosome ends. Mol Biochem Parasitol 106:169–174 (2000).
  32. Figeuiredo LM, Freitas-Junior LH, Bottius E, Olivo-Martin J-C, Schert A: A central role for Plasmodium falciparum subtelomeric regions in spatial positioning and telomere length regulation. EMBO J 21:815–824 (2002).
  33. Gerasimova TI, Byrd K, Corces VG: A chromatin insulator determines the nuclear localizations of DNA. Mol Cell 6:1025–1035 (2000).
  34. Gilbert N, Labuda D: CORE-SINEs: Eukaryotic short interspersed retroposing elements with common sequence motifs. Proc Natl Acad Sci USA 96:2869–2874 (1999).
  35. Han JS, Szak ST, Boeke JD: Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes. Nature 429:268–274 (2004).
  36. Hoskins RA, Smith CD, Carlson JW, Carvalho AB, Halpern A, Kaminker JS, Kennedy C, Mungall CJ, Sullivan BA, Sutton GG, Yasuhara JC, Wakimoto BT, Myers EW, Celniker SE, Rubin GM, Karpen GH: Heterochromatic sequences in a Drosophila whole-genome shotgun assembly. Genome Biol 3:0085.1–0085.16 (2002).
  37. Jordan IK, Rogozin IB, Glazko GV, Koonin EV: Origin of a substantial fraction of human regulatory sequences from transposable elements. Trends Genet 19:68–72 (2003).
  38. Jurka J, Zietkiewicz E, Labuda D: Ubiquitous mammalian-wide interspersed repeats (MIR) are molecular fossils from the Mesozoic era. Nucleic Acids Res 23:170–175 (1995).
  39. Kass DH, Kim J, Deininger PL: Sporadic amplification of ID elements in rodents. J Mol Evol 42:7–14 (1996).
  40. Kawai K, Nikaido M, Harada M, Matsumura S, Lim L-K, Wu Y, Hasegawa M, Okada N: Intra- and interfamily relationships of Vespertilionidae inferred by various molecular markers including SINE insertion data. J Mol Evol 55:284–301 (2002).
  41. Kazazian HH: L1 retrotransposons shape the mammalian genome. Science 289:1152–1153 (2000).
  42. Khodarev NN, Bennett T, Shearing N, Sokolova I, Koudelik J, Walter S, Villalobos M, Vaughn ATM: LINE L1 retrotransposable element is targeted during the initial stages of apoptotic DNA fragmentation. J Cell Biochem 79:486–495 (2000).
  43. Kramerov D, Vassetzky N, Serdobova I: The evolutionary position of dormice (Gliridae) in Rodentia determined by a novel short retroposon. Mol Biol Evol 16:715–717 (1999).
  44. Krane DE, Clark AG, Cheng J-F, Hardison R: Subfamily relationships and clustering of rabbit C repeats. Mol Biol Evol 8:1–30 (1991).
  45. Labrador M, Corces VG: Setting the boundaries of chromatin domains and nuclear organization. Cell 111:151–154 (2002).
  46. Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J, Reik W: Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35:88–93 (2003).
  47. Levanon EY, Eisenberg E, Yelin R, Nemzer S, Hallegger M, Shemesh R, Fligelman ZY, Shoshan A, Pollock SR, Sztybel D, Olshansky M, Rechavi G, Jantsch MF: Systematic identification of abundant A-to-I editing sites in the human transcriptome. Nat Biotechnol 22:1001–1005 (2004).
  48. Lin Z, Nomura O, Hayashi T, Wada Y, Yasue H: Characterization of a SINE species from vicuna and its distribution in animal species including the family Camelidae. Mamm Genome 12:305–308 (2001).
  49. Lippman Z, Gendrel A-V, Black M, Vaughn MW, Dedhia N, McCombie WR, Lavine K, Mittal V, May B, Kasschau KD, Carrington JC, Doerge RW, Colot V, Martienssen R: Role of transposable elements in heterochromatin and epigenetic control. Nature 430:471–476 (2004).
  50. Lyon MF: LINE-1 elements and X chromosome inactivation: a function for “junk” DNA? Proc Natl Acad Sci USA 97:6248–6249 (2000).
  51. Mallet F, Bouton O, Prudhomme S, Cheynet V, Oriol G, Bonnaud B, Lucotte G, Duret L, Mandrand B: The endogenous retroviral locus ERVWE1 is a bona fide gene involved in hominoid placental physiology. Proc Natl Acad Sci USA 101:1731–1736 (2004).
  52. Mayorov VI, Rogozin IB, Elisaphenko EA, Adkison LR: B2 elements are present in the human genome. Mamm Genome 11:177–179 (2000).
  53. Meyers BC, Tingey SV, Morgante M: Abundance, distribution, and transcriptional activity of repetitive elements in the maize genome. Genome Res 11:1660–1676 (2001).
  54. Miller JT, Dong F, Jackson SA, Song J, Jiang J: Retrotransposon-related DNA sequences in the centromeres of grass chromosomes. Genetics 150:1615–1623 (1998).
  55. Moran JV, DeBerardinis RJ, Kazazian HH: Exon shuffling by L1 retrotransposition. Science 283:1530–1534 (1999).
  56. Mozer BA, Benzer S: Ingrowth by photoreceptor axons induces transcription of a retrotransposon in the developing Drosophila brain. Development 120:1049–1058 (1994).
  57. Nabirochkin S, Ossokina M, Heidmann T: A nuclear matrix/scaffold attachment region co-localizes with the gypsy retrotransposon insulator sequence. J Biol Chem 273:2473–2479 (1998).
  58. Nagaki K, Song J, Stupar RM, Parokonny AS, Yuan Q, Ouyang S, Liu J, Hsiao J, Jones KM, Dawe RK, Buell CR, Jiang J: Molecular and cytological analyses of large tracks of centromeric DNA reveal the structure and evolutionary dynamics of maize centromeres. Genetics 163:759–770 (2003).
  59. Nekrutenko A, Li W-H: Transposable elements are found in a large number of human protein coding regions. Trends Genet 17:619–625 (2001).
  60. Nigumann P, Redik K, Matlik K, Speek M: Many human genes are transcribed from the antisense promoter of L1 retrotransposon. Genomics 79:628–634 (2002).
  61. Nikaido M, Matsuno F, Abe H, Shimamura M, Hamilton H, Matsubayashi H, Okada N: Evolution of CHR-2 SINEs in cetartiodactyl genomes: possible evidence for the monophyletic origin of toothed whales. Mamm Genome 12:909–915 (2001).
  62. Nikaido M, Nishihara H, Hukumoto Y, Okada N: Ancient SINEs from African endemic mammals. Mol Biol Evol 20:522–527 (2003).
  63. Norris J, Fan D, Aleman C, Marks JR, Futreal PA, Wiseman RW, Inglehart JD, Deininger PL, McDonnell DP: Identification of a new subclass of Alu DNA repeats which can function as estrogen receptor-dependent transcriptional enhancers. J Biol Chem 270:22777–22782 (1995).
  64. Pardue ML, DeBaryshe PG: Retrotransposons provide an evolutionarily robust non-telomerase mechanism to maintain telomeres. Ann Rev Genet 37:485–511 (2003).
  65. Parish DA, Vise P, Wichman HA, Bull JJ, Baker RJ: Distribution of LINEs and other repetitive elements in the karyotype of the bat Carollia: implications for X-chromosome inactivation. Cytogenet Genome Res 96:191–197 (2002).
  66. Pelissier T, Tutois S, Tourmente S, Deragon JM, Picard G: DNA regions flanking the major Arabidopsis thaliana satellite are principally enriched in Athila retroelement sequences. Genetica 97:141–151 (1996).
  67. Petrov DA: Evolution of genome size: new approaches to an old problem. Trends Genet 17:23–28 (2001).
  68. Pimpinelli S, Berloco M, Fanti L, Dimitri P, Bonaccorsi S, Marchetti E, Caizzi R, Caggese C, Gatti M: Transposable elements are stable structural components of Drosophila melanogaster heterochromatin. Proc Natl Acad Sci USA 92:3804–3808 (1995).
  69. Piskurek O, Nikaido M, Boeadi, Baba M, Okada N: Unique mammalian tRNA-derived repetitive elements in dermopterans: the t-SINE family and its retrotransposition through multiple sources. Mol Biol Evol 20:1659–1668 (2003).
  70. Rollini P, Namciu SJ, Marsden MD, Fournier REK: Identification and characterization of nuclear matrix-attachment regions in the human serpin gene cluster at 14q32.1. Nucleic Acids Res 27:3779–3791 (1999).
  71. Rubin CM, Kimura RH, Schmid CW: Selective stimulation of translational expression by Alu RNA. Nucleic Acids Res 30:3253–3261 (2002).
  72. Sakagami M, Hiromura K, Chemnick LG, Ryder OA: Distribution of the ERE-1 family in Perissodactyla. Mamm Genome 10:930–933 (1999).
  73. Schmid C: Alu: structure, origin, evolution, significance, and function of one-tenth of human DNA. Prog Nucl Acids Res Mol Biol 53:283–319 (1996).
  74. Scholes DT, Kenny AE, Gamache ER, Mou Z, Curcio MJ: Activation of an LTR-retrotransposon by telomere erosion. Proc Natl Acad Sci USA 100:15736–15741 (2003).
  75. Shapiro JA: Genome system architecture and natural genetic engineering in evolution. Ann NY Acad Sci 870:23–35 (1999).
  76. Shapiro JA: Genome organization and reorganization in evolution: formatting for computation and function. Ann NY Acad Sci 981:111–134 (2002).
  77. Shapiro JA, Sternberg RV: Why repetitive DNA is essential for genome function. Biol Rev (in press 2004).
  78. Shimamura M, Abe H, Nikaido M, Ohshima K, Okada N: Genealogy of families of SINEs in cetaceans and artiodactyls: the presence of a huge superfamily of tRNA(Glu)-derived families of SINEs. Mol Biol Evol 16:1046–1060 (1999).
  79. Silva JC, Shabalina SA, Harris DG, Spouge JL, Kondrashovi AS: Conserved fragments of transposable elements in intergenic regions: evidence for widespread recruitment of MIR- and L2-derived sequences within the mouse and human genomes. Genet Res 82:1–18 (2003).
  80. Skyrabin BV, Kremerskothen J, Vassilacopoulou D, Disotell TR, Kapatinov VV, Jorka J, Brosius J: The BC200 RNA gene and its neural expression are conserved in Anthropoidea (primates). J Mol Evol 47:677–685 (1998).
  81. Song X, Sui A, Garen A: Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: Effects on steroidogenesis and oncogenesis. Proc Natl Acad Sci USA 101:621–626 (2004).
  82. Speek M: Antisense promoter of human L1 retrotransposon drives transcription of adjacent cellular genes. Mol Cell Biol 21:1973–1985 (2001).
  83. Sternberg RV: The role of constrained self-organization in genome structural evolution. Acta Biotheor 44:95–118 (1996).
  84. Sternberg RV: Genomes and form. The case for teleomorphic recursivity. Ann NY Acad Sci 901:224–236 (2000).
  85. Sternberg RV: On the roles of repetitive DNA elements in the context of a unified genomic-epigenetic system. Ann NY Acad Sci 981:154–188 (2002).
  86. Tchénio T, Casella J-F, Heidmann T: Members of the SRY family regulate the human LINE retrotransposons. Nucleic Acids Res 28:411–415 (2000).
  87. van Driel R, Fransz PF, Verschure PJ: The eukaryotic genome: a system regulated at different hierarchical levels. J Cell Sci 116:4067–4075 (2003).
  88. Vansant G, Reynolds WF: The consensus sequence of a major Alu subfamily contains a functional retinoic acid response element. Proc Natl Acad Sci USA 92:8229–8233 (1995).
  89. Vassetzky NS, Kramerov DA: CAN – a pan-carnivore SINE family. Mamm Genome 13:50–57 (2002).
  90. Vassetzky NS, Ten OA, Kramerov DA: B1 and related SINEs in mammalian genomes. Gene 319:149–160 (2003).
  91. Watson JB, Sutcliffe JG: Primate brain-specific cytoplasmic transcript of the Alu repeat family. Mol Cell Biol 7:3324–3327 (1987).
  92. Wyrick JJ, Aparicio JG, Chen T, Barnett JD, Jennings EG, Young RA, Bell SP, Aparicio OM: Genome-wide distribution of ORC and MCM proteins in S. cerevisiae: high-resolution mapping of replication origins. Science 14:2357–2360 (2001).
  93. Yang Z, Bofelli D, Boonmark N, Schwartz K, Lawn R: Apolipoprotein(a) gene enhancer resides within a LINE element. J Biol Chem 273:891–897 (1998).
  94. Yates PA, Burman RW, Mummaneni P, Krussel S, Turker MS: Tandem B1 elements located in a mouse methylation center provide a target for de novo DNA methylation. J Biol Chem 274:36357–36361 (1999).
  95. Zaiss DMW, Kloetzel P-M: A second gene encoding the mouse proteosome activator b subunit is part of a LINE1 element and is driven by a LINE1 promoter. J Mol Biol 287:829–835 (1999).
  96. Zehr SM, Nedbal MA, Flynn JJ: Tempo and mode of evolution in an orthologous Can SINE. Mamm Genome 12:38–44 (2001).
  97. Zhang X, Wessler SR: Genome-wide comparative analysis of the transposable elements in the related species Arabidopsis thaliana and Brassica oleracea. Proc Natl Acad Sci USA 101:5589–5594 (2004).
  98. Zhong CX, Marshall JB, Topp C, Mroczek R, Kato A, Nagaki K, Birchler JA, Jiang J, Dawe RK: Centromeric retroelements and satellites interact with maize kinetochore protein CENH3. Plant Cell 14:2825–2836 (2002).
  99. Zhou Y-H, Zheng JB, Gu X, Li W-H, Saunders GF: A novel Pax-6 binding site in rodent B1 repetitive elements: coevolution between developmental regulation and repeated elements? Gene 245:319–328 (2000).
  100. Zhou Y-H, Zheng JB, Gu X, Saunders GF, Yung W-KA: Novel Pax6 binding sites in the human genome and the role of repetitive elements in the evolution of gene regulation. Genome Res 12:1716–1722 (2002).
  101. Zhu L, Swergold GD, Seldin MF: Examination of sequence homology between human chromosome 20 and the mouse genome: intense conservation of many genomic elements. Hum Genet 113:60–70 (2003).
  102. Zuckerkandl E: Why so many noncoding nucleotides? The eukaryote genome as an epigenetic machine. Genetica 115:105–129 (2002).

Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50