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. 2000 Jan;154(1):193–203. doi: 10.1093/genetics/154.1.193

NeSL-1, an ancient lineage of site-specific non-LTR retrotransposons from Caenorhabditis elegans.

H S Malik 1, T H Eickbush 1
PMCID: PMC1460889  PMID: 10628980

Abstract

Phylogenetic analyses of non-LTR retrotransposons suggest that all elements can be divided into 11 lineages. The 3 oldest lineages show target site specificity for unique locations in the genome and encode an endonuclease with an active site similar to certain restriction enzymes. The more "modern" non-LTR lineages possess an apurinic endonuclease-like domain and generally lack site specificity. The genome sequence of Caenorhabditis elegans reveals the presence of a non-LTR retrotransposon that resembles the older elements, in that it contains a single open reading frame with a carboxyl-terminal restriction-like endonuclease domain. Located near the N-terminal end of the ORF is a cysteine protease domain not found in any other non-LTR element. The N2 strain of C. elegans appears to contain only one full-length and several 5' truncated copies of this element. The elements specifically insert in the Spliced leader-1 genes; hence the element has been named NeSL-1 (Nematode Spliced Leader-1). Phylogenetic analysis confirms that NeSL-1 branches very early in the non-LTR lineage and that it represents a 12th lineage of non-LTR elements. The target specificity of NeSL-1 for the spliced leader exons and the similarity of its structure to that of R2 elements leads to a simple model for its expression and retrotransposition.

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Selected References

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  1. Agrawal A., Eastman Q. M., Schatz D. G. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature. 1998 Aug 20;394(6695):744–751. doi: 10.1038/29457. [DOI] [PubMed] [Google Scholar]
  2. Aksoy S., Williams S., Chang S., Richards F. F. SLACS retrotransposon from Trypanosoma brucei gambiense is similar to mammalian LINEs. Nucleic Acids Res. 1990 Feb 25;18(4):785–792. doi: 10.1093/nar/18.4.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bektesh S., Van Doren K., Hirsh D. Presence of the Caenorhabditis elegans spliced leader on different mRNAs and in different genera of nematodes. Genes Dev. 1988 Oct;2(10):1277–1283. doi: 10.1101/gad.2.10.1277. [DOI] [PubMed] [Google Scholar]
  5. Berg J. M., Shi Y. The galvanization of biology: a growing appreciation for the roles of zinc. Science. 1996 Feb 23;271(5252):1081–1085. doi: 10.1126/science.271.5252.1081. [DOI] [PubMed] [Google Scholar]
  6. Burke W. D., Malik H. S., Jones J. P., Eickbush T. H. The domain structure and retrotransposition mechanism of R2 elements are conserved throughout arthropods. Mol Biol Evol. 1999 Apr;16(4):502–511. doi: 10.1093/oxfordjournals.molbev.a026132. [DOI] [PubMed] [Google Scholar]
  7. Burke W. D., Malik H. S., Lathe W. C., 3rd, Eickbush T. H. Are retrotransposons long-term hitchhikers? Nature. 1998 Mar 12;392(6672):141–142. doi: 10.1038/32330. [DOI] [PubMed] [Google Scholar]
  8. Burke W. D., Müller F., Eickbush T. H. R4, a non-LTR retrotransposon specific to the large subunit rRNA genes of nematodes. Nucleic Acids Res. 1995 Nov 25;23(22):4628–4634. doi: 10.1093/nar/23.22.4628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. C. elegans Sequencing Consortium Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012–2018. doi: 10.1126/science.282.5396.2012. [DOI] [PubMed] [Google Scholar]
  10. Clark J. B., Maddison W. P., Kidwell M. G. Phylogenetic analysis supports horizontal transfer of P transposable elements. Mol Biol Evol. 1994 Jan;11(1):40–50. doi: 10.1093/oxfordjournals.molbev.a040091. [DOI] [PubMed] [Google Scholar]
  11. Davis R. E., Singh H., Botka C., Hardwick C., Ashraf el Meanawy M., Villanueva J. RNA trans-splicing in Fasciola hepatica. Identification of a spliced leader (SL) RNA and SL sequences on mRNAs. J Biol Chem. 1994 Aug 5;269(31):20026–20030. [PubMed] [Google Scholar]
  12. Eickbush D. G., Eickbush T. H. Vertical transmission of the retrotransposable elements R1 and R2 during the evolution of the Drosophila melanogaster species subgroup. Genetics. 1995 Feb;139(2):671–684. doi: 10.1093/genetics/139.2.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Evans D., Zorio D., MacMorris M., Winter C. E., Lea K., Blumenthal T. Operons and SL2 trans-splicing exist in nematodes outside the genus Caenorhabditis. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9751–9756. doi: 10.1073/pnas.94.18.9751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Feng Q., Moran J. V., Kazazian H. H., Jr, Boeke J. D. Human L1 retrotransposon encodes a conserved endonuclease required for retrotransposition. Cell. 1996 Nov 29;87(5):905–916. doi: 10.1016/s0092-8674(00)81997-2. [DOI] [PubMed] [Google Scholar]
  15. Gabriel A., Yen T. J., Schwartz D. C., Smith C. L., Boeke J. D., Sollner-Webb B., Cleveland D. W. A rapidly rearranging retrotransposon within the miniexon gene locus of Crithidia fasciculata. Mol Cell Biol. 1990 Feb;10(2):615–624. doi: 10.1128/mcb.10.2.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. George J. A., Eickbush T. H. Conserved features at the 5 end of Drosophila R2 retrotransposable elements: implications for transcription and translation. Insect Mol Biol. 1999 Feb;8(1):3–10. doi: 10.1046/j.1365-2583.1999.810003.x. [DOI] [PubMed] [Google Scholar]
  17. Gonzalez P., Lessios H. A. Evolution of sea urchin retroviral-like (SURL) elements: evidence from 40 echinoid species. Mol Biol Evol. 1999 Jul;16(7):938–952. doi: 10.1093/oxfordjournals.molbev.a026183. [DOI] [PubMed] [Google Scholar]
  18. Hartl D. L., Lohe A. R., Lozovskaya E. R. Modern thoughts on an ancyent marinere: function, evolution, regulation. Annu Rev Genet. 1997;31:337–358. doi: 10.1146/annurev.genet.31.1.337. [DOI] [PubMed] [Google Scholar]
  19. Jakubczak J. L., Zenni M. K., Woodruff R. C., Eickbush T. H. Turnover of R1 (type I) and R2 (type II) retrotransposable elements in the ribosomal DNA of Drosophila melanogaster. Genetics. 1992 May;131(1):129–142. doi: 10.1093/genetics/131.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kazazian H. H., Jr, Moran J. V. The impact of L1 retrotransposons on the human genome. Nat Genet. 1998 May;19(1):19–24. doi: 10.1038/ng0598-19. [DOI] [PubMed] [Google Scholar]
  21. Krause M., Hirsh D. A trans-spliced leader sequence on actin mRNA in C. elegans. Cell. 1987 Jun 19;49(6):753–761. doi: 10.1016/0092-8674(87)90613-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lathe W. C., 3rd, Burke W. D., Eickbush D. G., Eickbush T. H. Evolutionary stability of the R1 retrotransposable element in the genus Drosophila. Mol Biol Evol. 1995 Nov;12(6):1094–1105. doi: 10.1093/oxfordjournals.molbev.a040283. [DOI] [PubMed] [Google Scholar]
  23. Lathe W. C., 3rd, Eickbush T. H. A single lineage of r2 retrotransposable elements is an active, evolutionarily stable component of the Drosophila rDNA locus. Mol Biol Evol. 1997 Dec;14(12):1232–1241. doi: 10.1093/oxfordjournals.molbev.a025732. [DOI] [PubMed] [Google Scholar]
  24. Levis R. W., Ganesan R., Houtchens K., Tolar L. A., Sheen F. M. Transposons in place of telomeric repeats at a Drosophila telomere. Cell. 1993 Dec 17;75(6):1083–1093. doi: 10.1016/0092-8674(93)90318-k. [DOI] [PubMed] [Google Scholar]
  25. Li S. J., Hochstrasser M. A new protease required for cell-cycle progression in yeast. Nature. 1999 Mar 18;398(6724):246–251. doi: 10.1038/18457. [DOI] [PubMed] [Google Scholar]
  26. Liou R. F., Blumenthal T. trans-spliced Caenorhabditis elegans mRNAs retain trimethylguanosine caps. Mol Cell Biol. 1990 Apr;10(4):1764–1768. doi: 10.1128/mcb.10.4.1764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Luan D. D., Korman M. H., Jakubczak J. L., Eickbush T. H. Reverse transcription of R2Bm RNA is primed by a nick at the chromosomal target site: a mechanism for non-LTR retrotransposition. Cell. 1993 Feb 26;72(4):595–605. doi: 10.1016/0092-8674(93)90078-5. [DOI] [PubMed] [Google Scholar]
  28. Malik H. S., Eickbush T. H. The RTE class of non-LTR retrotransposons is widely distributed in animals and is the origin of many SINEs. Mol Biol Evol. 1998 Sep;15(9):1123–1134. doi: 10.1093/oxfordjournals.molbev.a026020. [DOI] [PubMed] [Google Scholar]
  29. Marín I., Plata-Rengifo P., Labrador M., Fontdevila A. Evolutionary relationships among the members of an ancient class of non-LTR retrotransposons found in the nematode Caenorhabditis elegans. Mol Biol Evol. 1998 Nov;15(11):1390–1402. doi: 10.1093/oxfordjournals.molbev.a025867. [DOI] [PubMed] [Google Scholar]
  30. Nakamura T. M., Morin G. B., Chapman K. B., Weinrich S. L., Andrews W. H., Lingner J., Harley C. B., Cech T. R. Telomerase catalytic subunit homologs from fission yeast and human. Science. 1997 Aug 15;277(5328):955–959. doi: 10.1126/science.277.5328.955. [DOI] [PubMed] [Google Scholar]
  31. Nelson D. W., Honda B. M. Genes coding for 5S ribosomal RNA of the nematode Caenorhabditis elegans. Gene. 1985;38(1-3):245–251. doi: 10.1016/0378-1119(85)90224-0. [DOI] [PubMed] [Google Scholar]
  32. Nilsen T. W., Shambaugh J., Denker J., Chubb G., Faser C., Putnam L., Bennett K. Characterization and expression of a spliced leader RNA in the parasitic nematode Ascaris lumbricoides var. suum. Mol Cell Biol. 1989 Aug;9(8):3543–3547. doi: 10.1128/mcb.9.8.3543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Pardue M. L., Danilevskaya O. N., Lowenhaupt K., Slot F., Traverse K. L. Drosophila telomeres: new views on chromosome evolution. Trends Genet. 1996 Feb;12(2):48–52. doi: 10.1016/0168-9525(96)81399-0. [DOI] [PubMed] [Google Scholar]
  34. Pardue M. L., Danilevskaya O. N., Lowenhaupt K., Slot F., Traverse K. L. Drosophila telomeres: new views on chromosome evolution. Trends Genet. 1996 Feb;12(2):48–52. doi: 10.1016/0168-9525(96)81399-0. [DOI] [PubMed] [Google Scholar]
  35. Rajkovic A., Davis R. E., Simonsen J. N., Rottman F. M. A spliced leader is present on a subset of mRNAs from the human parasite Schistosoma mansoni. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8879–8883. doi: 10.1073/pnas.87.22.8879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Robertson H. M. Multiple Mariner transposons in flatworms and hydras are related to those of insects. J Hered. 1997 May-Jun;88(3):195–201. doi: 10.1093/oxfordjournals.jhered.a023088. [DOI] [PubMed] [Google Scholar]
  37. Ross L. H., Freedman J. H., Rubin C. S. Structure and expression of novel spliced leader RNA genes in Caenorhabditis elegans. J Biol Chem. 1995 Sep 15;270(37):22066–22075. doi: 10.1074/jbc.270.37.22066. [DOI] [PubMed] [Google Scholar]
  38. Saitou N., Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. doi: 10.1093/oxfordjournals.molbev.a040454. [DOI] [PubMed] [Google Scholar]
  39. Song S. U., Gerasimova T., Kurkulos M., Boeke J. D., Corces V. G. An env-like protein encoded by a Drosophila retroelement: evidence that gypsy is an infectious retrovirus. Genes Dev. 1994 Sep 1;8(17):2046–2057. doi: 10.1101/gad.8.17.2046. [DOI] [PubMed] [Google Scholar]
  40. Springer M. S., Britten R. J. Phylogenetic relationships of reverse transcriptase and RNase H sequences and aspects of genome structure in the gypsy group of retrotransposons. Mol Biol Evol. 1993 Nov;10(6):1370–1379. doi: 10.1093/oxfordjournals.molbev.a040065. [DOI] [PubMed] [Google Scholar]
  41. Tessier L. H., Keller M., Chan R. L., Fournier R., Weil J. H., Imbault P. Short leader sequences may be transferred from small RNAs to pre-mature mRNAs by trans-splicing in Euglena. EMBO J. 1991 Sep;10(9):2621–2625. doi: 10.1002/j.1460-2075.1991.tb07804.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Thompson J. D., Gibson T. J., Plewniak F., Jeanmougin F., Higgins D. G. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 1997 Dec 15;25(24):4876–4882. doi: 10.1093/nar/25.24.4876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Villanueva M. S., Williams S. P., Beard C. B., Richards F. F., Aksoy S. A new member of a family of site-specific retrotransposons is present in the spliced leader RNA genes of Trypanosoma cruzi. Mol Cell Biol. 1991 Dec;11(12):6139–6148. doi: 10.1128/mcb.11.12.6139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wah D. A., Hirsch J. A., Dorner L. F., Schildkraut I., Aggarwal A. K. Structure of the multimodular endonuclease FokI bound to DNA. Nature. 1997 Jul 3;388(6637):97–100. doi: 10.1038/40446. [DOI] [PubMed] [Google Scholar]
  45. Waugh D. S., Sauer R. T. Single amino acid substitutions uncouple the DNA binding and strand scission activities of Fok I endonuclease. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9596–9600. doi: 10.1073/pnas.90.20.9596. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Winkler F. K., Banner D. W., Oefner C., Tsernoglou D., Brown R. S., Heathman S. P., Bryan R. K., Martin P. D., Petratos K., Wilson K. S. The crystal structure of EcoRV endonuclease and of its complexes with cognate and non-cognate DNA fragments. EMBO J. 1993 May;12(5):1781–1795. doi: 10.2210/pdb4rve/pdb. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Xie H., Bain O., Williams S. A. Molecular phylogenetic studies on filarial parasites based on 5S ribosomal spacer sequences. Parasite. 1994 Jun;1(2):141–151. doi: 10.1051/parasite/1994012141. [DOI] [PubMed] [Google Scholar]
  48. Xiong Y. E., Eickbush T. H. Functional expression of a sequence-specific endonuclease encoded by the retrotransposon R2Bm. Cell. 1988 Oct 21;55(2):235–246. doi: 10.1016/0092-8674(88)90046-3. [DOI] [PubMed] [Google Scholar]
  49. Xiong Y., Burke W. D., Jakubczak J. L., Eickbush T. H. Ribosomal DNA insertion elements R1Bm and R2Bm can transpose in a sequence specific manner to locations outside the 28S genes. Nucleic Acids Res. 1988 Nov 25;16(22):10561–10573. doi: 10.1093/nar/16.22.10561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Xiong Y., Eickbush T. H. Dong, a non-long terminal repeat (non-LTR) retrotransposable element from Bombyx mori. Nucleic Acids Res. 1993 Mar 11;21(5):1318–1318. doi: 10.1093/nar/21.5.1318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Zorio D. A., Cheng N. N., Blumenthal T., Spieth J. Operons as a common form of chromosomal organization in C. elegans. Nature. 1994 Nov 17;372(6503):270–272. doi: 10.1038/372270a0. [DOI] [PubMed] [Google Scholar]

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