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. 1997 Jun;146(2):641–654. doi: 10.1093/genetics/146.2.641

Recombination Creates Novel L1 (Line-1) Elements in Rattus Norvegicus

B E Hayward 1, M Zavanelli 1, A V Furano 1
PMCID: PMC1208004  PMID: 9178013

Abstract

Mammalian L1 (long interspersed repeated DNA, LINE-1) retrotransposons consist of a 5' untranslated region (UTR) with regulatory properties, two protein encoding regions (ORF I, ORF II, which encodes a reverse transcriptase) and a 3' UTR. L1 elements have been evolving in mammals for >100 million years and this process continues to generate novel L1 subfamilies in modern species. Here we characterized the youngest known subfamily in Rattus norvegicus, L1(mlvi2), and unexpectedly found that this element has a dual ancestry. While its 3' UTR shares the same lineage as its nearest chronologically antecedent subfamilies, L1(3) and L1(4), its ORF I sequence does not. The L1(mlvi2) ORF I was derived from an ancestral ORF I sequence that was the evolutionary precursor of the L1(3) and L1(4) ORF I. We suggest that an ancestral ORF I sequence was recruited into the modern L1(mlvi2) subfamily by recombination that possibly could have resulted from template strand switching by the reverse transcriptase during L1 replication. This mechanism could also account for some of the structural features of rodent L1 5' UTR and ORF I sequences including one of the more dramatic features of L1 evolution in mammals, namely the repeated acquisition of novel 5' UTRs.

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Selected References

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  1. Adey N. B., Schichman S. A., Graham D. K., Peterson S. N., Edgell M. H., Hutchison C. A., 3rd Rodent L1 evolution has been driven by a single dominant lineage that has repeatedly acquired new transcriptional regulatory sequences. Mol Biol Evol. 1994 Sep;11(5):778–789. doi: 10.1093/oxfordjournals.molbev.a040158. [DOI] [PubMed] [Google Scholar]
  2. Adey N. B., Schichman S. A., Hutchison C. A., 3rd, Edgell M. H. Composite of A and F-type 5' terminal sequences defines a subfamily of mouse LINE-1 elements. J Mol Biol. 1991 Sep 20;221(2):367–373. doi: 10.1016/0022-2836(91)80057-2. [DOI] [PubMed] [Google Scholar]
  3. Bellis M., Jubier-Maurin V., Dod B., Vanlerberghe F., Laurent A. M., Senglat C., Bonhomme F., Roizès G. Distributions of two recently inserted long interspersed elements of the L1 repetitive family at the Alb and beta h3 loci in wild mice populations. Mol Biol Evol. 1987 Jul;4(4):351–363. doi: 10.1093/oxfordjournals.molbev.a040449. [DOI] [PubMed] [Google Scholar]
  4. Casavant N. C., Hardies S. C., Funk F. D., Comer M. B., Edgell M. H., Hutchison C. A., 3rd Extensive movement of LINES ONE sequences in beta-globin loci of Mus caroli and Mus domesticus. Mol Cell Biol. 1988 Nov;8(11):4669–4674. doi: 10.1128/mcb.8.11.4669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Casavant N. C., Hardies S. C. Shared sequence variants of Mus spretus LINE-1 elements tracing dispersal to within the last 1 million years. Genetics. 1994 Jun;137(2):565–572. doi: 10.1093/genetics/137.2.565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Casavant N. C., Hardies S. C. The dynamics of murine LINE-1 subfamily amplification. J Mol Biol. 1994 Aug 19;241(3):390–397. doi: 10.1006/jmbi.1994.1515. [DOI] [PubMed] [Google Scholar]
  7. Demers G. W., Matunis M. J., Hardison R. C. The L1 family of long interspersed repetitive DNA in rabbits: sequence, copy number, conserved open reading frames, and similarity to keratin. J Mol Evol. 1989 Jul;29(1):3–19. doi: 10.1007/BF02106177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Deragon J. M., Sinnett D., Labuda D. Reverse transcriptase activity from human embryonal carcinoma cells NTera2D1. EMBO J. 1990 Oct;9(10):3363–3368. doi: 10.1002/j.1460-2075.1990.tb07537.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dombroski B. A., Scott A. F., Kazazian H. H., Jr Two additional potential retrotransposons isolated from a human L1 subfamily that contains an active retrotransposable element. Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6513–6517. doi: 10.1073/pnas.90.14.6513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Economou-Pachnis A., Lohse M. A., Furano A. V., Tsichlis P. N. Insertion of long interspersed repeated elements at the Igh (immunoglobulin heavy chain) and Mlvi-2 (Moloney leukemia virus integration 2) loci of rats. Proc Natl Acad Sci U S A. 1985 May;82(9):2857–2861. doi: 10.1073/pnas.82.9.2857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fanning T. G. Size and structure of the highly repetitive BAM HI element in mice. Nucleic Acids Res. 1983 Aug 11;11(15):5073–5091. doi: 10.1093/nar/11.15.5073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Furano A. V., Hayward B. E., Chevret P., Catzeflis F., Usdin K. Amplification of the ancient murine Lx family of long interspersed repeated DNA occurred during the murine radiation. J Mol Evol. 1994 Jan;38(1):18–27. doi: 10.1007/BF00175491. [DOI] [PubMed] [Google Scholar]
  13. Furano A. V., Robb S. M., Robb F. T. The structure of the regulatory region of the rat L1 (L1Rn, long interspersed repeated) DNA family of transposable elements. Nucleic Acids Res. 1988 Oct 11;16(19):9215–9231. doi: 10.1093/nar/16.19.9215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hajjar A. M., Linial M. L. A model system for nonhomologous recombination between retroviral and cellular RNA. J Virol. 1993 Jul;67(7):3845–3853. doi: 10.1128/jvi.67.7.3845-3853.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hardison R., Miller W. Use of long sequence alignments to study the evolution and regulation of mammalian globin gene clusters. Mol Biol Evol. 1993 Jan;10(1):73–102. doi: 10.1093/oxfordjournals.molbev.a039991. [DOI] [PubMed] [Google Scholar]
  16. Holmes S. E., Dombroski B. A., Krebs C. M., Boehm C. D., Kazazian H. H., Jr A new retrotransposable human L1 element from the LRE2 locus on chromosome 1q produces a chimaeric insertion. Nat Genet. 1994 Jun;7(2):143–148. doi: 10.1038/ng0694-143. [DOI] [PubMed] [Google Scholar]
  17. Jubier-Maurin V., Cuny G., Laurent A. M., Paquereau L., Roizes G. A new 5' sequence associated with mouse L1 elements is representative of a major class of L1 termini. Mol Biol Evol. 1992 Jan;9(1):41–55. doi: 10.1093/oxfordjournals.molbev.a040707. [DOI] [PubMed] [Google Scholar]
  18. Kameda T., Akahori A., Sonobe M. H., Suzuki T., Endo T., Iba H. JunD mutants with spontaneously acquired transforming potential have enhanced transactivating activity in combination with Fra-2. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9369–9373. doi: 10.1073/pnas.90.20.9369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kazazian H. H., Jr, Wong C., Youssoufian H., Scott A. F., Phillips D. G., Antonarakis S. E. Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Nature. 1988 Mar 10;332(6160):164–166. doi: 10.1038/332164a0. [DOI] [PubMed] [Google Scholar]
  20. Kolosha V. O., Martin S. L. Polymorphic sequences encoding the first open reading frame protein from LINE-1 ribonucleoprotein particles. J Biol Chem. 1995 Feb 10;270(6):2868–2873. doi: 10.1074/jbc.270.6.2868. [DOI] [PubMed] [Google Scholar]
  21. Kozak M. An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res. 1987 Oct 26;15(20):8125–8148. doi: 10.1093/nar/15.20.8125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kurose K., Hata K., Hattori M., Sakaki Y. RNA polymerase III dependence of the human L1 promoter and possible participation of the RNA polymerase II factor YY1 in the RNA polymerase III transcription system. Nucleic Acids Res. 1995 Sep 25;23(18):3704–3709. doi: 10.1093/nar/23.18.3704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lakshmikumaran M. S., D'Ambrosio E., Laimins L. A., Lin D. T., Furano A. V. Long interspersed repeated DNA (LINE) causes polymorphism at the rat insulin 1 locus. Mol Cell Biol. 1985 Sep;5(9):2197–2203. doi: 10.1128/mcb.5.9.2197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Luan D. D., Eickbush T. H. RNA template requirements for target DNA-primed reverse transcription by the R2 retrotransposable element. Mol Cell Biol. 1995 Jul;15(7):3882–3891. doi: 10.1128/mcb.15.7.3882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Martin S. L. Ribonucleoprotein particles with LINE-1 RNA in mouse embryonal carcinoma cells. Mol Cell Biol. 1991 Sep;11(9):4804–4807. doi: 10.1128/mcb.11.9.4804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mathias S. L., Scott A. F., Kazazian H. H., Jr, Boeke J. D., Gabriel A. Reverse transcriptase encoded by a human transposable element. Science. 1991 Dec 20;254(5039):1808–1810. doi: 10.1126/science.1722352. [DOI] [PubMed] [Google Scholar]
  27. Miki Y., Nishisho I., Horii A., Miyoshi Y., Utsunomiya J., Kinzler K. W., Vogelstein B., Nakamura Y. Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer. Cancer Res. 1992 Feb 1;52(3):643–645. [PubMed] [Google Scholar]
  28. Minakami R., Kurose K., Etoh K., Furuhata Y., Hattori M., Sakaki Y. Identification of an internal cis-element essential for the human L1 transcription and a nuclear factor(s) binding to the element. Nucleic Acids Res. 1992 Jun 25;20(12):3139–3145. doi: 10.1093/nar/20.12.3139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nur I., Pascale E., Furano A. V. The left end of rat L1 (L1Rn, long interspersed repeated) DNA which is a CpG island can function as a promoter. Nucleic Acids Res. 1988 Oct 11;16(19):9233–9251. doi: 10.1093/nar/16.19.9233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Padgett R. W., Hutchison C. A., 3rd, Edgell M. H. The F-type 5' motif of mouse L1 elements: a major class of L1 termini similar to the A-type in organization but unrelated in sequence. Nucleic Acids Res. 1988 Jan 25;16(2):739–749. doi: 10.1093/nar/16.2.739. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pascale E., Valle E., Furano A. V. Amplification of an ancestral mammalian L1 family of long interspersed repeated DNA occurred just before the murine radiation. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9481–9485. doi: 10.1073/pnas.87.23.9481. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schichman S. A., Severynse D. M., Edgell M. H., Hutchison C. A., 3rd Strand-specific LINE-1 transcription in mouse F9 cells originates from the youngest phylogenetic subgroup of LINE-1 elements. J Mol Biol. 1992 Apr 5;224(3):559–574. doi: 10.1016/0022-2836(92)90544-t. [DOI] [PubMed] [Google Scholar]
  33. Scott A. F., Schmeckpeper B. J., Abdelrazik M., Comey C. T., O'Hara B., Rossiter J. P., Cooley T., Heath P., Smith K. D., Margolet L. Origin of the human L1 elements: proposed progenitor genes deduced from a consensus DNA sequence. Genomics. 1987 Oct;1(2):113–125. doi: 10.1016/0888-7543(87)90003-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Severynse D. M., Hutchison C. A., 3rd, Edgell M. H. Identification of transcriptional regulatory activity within the 5' A-type monomer sequence of the mouse LINE-1 retroposon. Mamm Genome. 1992;2(1):41–50. doi: 10.1007/BF00570439. [DOI] [PubMed] [Google Scholar]
  35. Smit A. F., Tóth G., Riggs A. D., Jurka J. Ancestral, mammalian-wide subfamilies of LINE-1 repetitive sequences. J Mol Biol. 1995 Feb 24;246(3):401–417. doi: 10.1006/jmbi.1994.0095. [DOI] [PubMed] [Google Scholar]
  36. Soares M. B., Schon E., Efstratiadis A. Rat LINE1: the origin and evolution of a family of long interspersed middle repetitive DNA elements. J Mol Evol. 1985;22(2):117–133. doi: 10.1007/BF02101690. [DOI] [PubMed] [Google Scholar]
  37. Usdin K., Chevret P., Catzeflis F. M., Verona R., Furano A. V. L1 (LINE-1) retrotransposable elements provide a "fossil" record of the phylogenetic history of murid rodents. Mol Biol Evol. 1995 Jan;12(1):73–82. doi: 10.1093/oxfordjournals.molbev.a040192. [DOI] [PubMed] [Google Scholar]
  38. Usdin K., Furano A. V. Rat L (long interspersed repeated DNA) elements contain guanine-rich homopurine sequences that induce unpairing of contiguous duplex DNA. Proc Natl Acad Sci U S A. 1988 Jun;85(12):4416–4420. doi: 10.1073/pnas.85.12.4416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Usdin K., Furano A. V. The structure of the guanine-rich polypurine:polypyrimidine sequence at the right end of the rat L1 (LINE) element. J Biol Chem. 1989 Sep 15;264(26):15681–15687. [PubMed] [Google Scholar]
  40. Voliva C. F., Jahn C. L., Comer M. B., Hutchison C. A., 3rd, Edgell M. H. The L1Md long interspersed repeat family in the mouse: almost all examples are truncated at one end. Nucleic Acids Res. 1983 Dec 20;11(24):8847–8859. doi: 10.1093/nar/11.24.8847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Voliva C. F., Martin S. L., Hutchison C. A., 3rd, Edgell M. H. Dispersal process associated with the L1 family of interspersed repetitive DNA sequences. J Mol Biol. 1984 Oct 5;178(4):795–813. doi: 10.1016/0022-2836(84)90312-7. [DOI] [PubMed] [Google Scholar]
  42. Wincker P., Jubier-Maurin V., Roizès G. Unrelated sequences at the 5' end of mouse LINE-1 repeated elements define two distinct subfamilies. Nucleic Acids Res. 1987 Nov 11;15(21):8593–8606. doi: 10.1093/nar/15.21.8593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Zhang J., Temin H. M. Rate and mechanism of nonhomologous recombination during a single cycle of retroviral replication. Science. 1993 Jan 8;259(5092):234–238. doi: 10.1126/science.8421784. [DOI] [PubMed] [Google Scholar]

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