Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Rapid amplification of a retrotransposon subfamily is evolving the mouse genome

Abstract

Retrotransposition affects genome structure by increasing repetition and producing insertional mutations1,2. Dispersion of the retrotransposon L1 throughout mammalian genomes suggests that L1 activity might be an important evolutionary force1. Here we report that L1 retrotransposition contributes to rapid genome evolution in the mouse, because a number of L1 sequences from the TF subfamily are retrotransposition competent. We show that the TF subfamily is large, young and expanding, containing approximately 4,800 full-length members in strain 129. Eleven randomly isolated, full-length TF elements averaged 99.8% sequence identity to each other, and seven of these retrotransposed in cultured cells. Thus, we estimate that the mouse genome contains approximately 3,000 active TF elements, 75 times the estimated number of active human L1s. Moreover, as TF elements are polymorphic among closely related mice, they have retrotransposed recently, implying rapid amplification of the subfamily to yield genomes with different patterns of interspersed repetition. Our data show that mice and humans differ considerably in the number of active L1s, and probably differ in the contribution of retrotransposition to ongoing sequence evolution.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Eleven randomly cloned TF elements are nearly identical to each other.
Figure 2: TF elements are recent insertions.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Hutchison, C.A. III, Hardies, S.C., Loeb, D.D., Shehee, W.R. & Edgell, M.H. LINEs and related retrotransposons: long interspersed repeated sequences in the eucaryotic genome. in Mobile DNA (eds Berg, D.E. & Howe, M.H.) 593–617 (Amer. Soc. Microbiol., Washington, DC, 1989).

  2. Kazazian, H.H. & Moran, J.V. The impact of L1 retrotransposons on the human genome. Nature Genet. 19, 19–24 (1998).

    Article  CAS  Google Scholar 

  3. Fanning, T.G. Size and structure of the highly-repetitive BamHI element in mice. Nucleic Acids Res. 11, 5073– 5091 (1983).

    Article  CAS  Google Scholar 

  4. Loeb, D.D. et al. The sequence of a large L1Md element reveals a tandemly repeated 5' end and several features found in retrotransposons . Mol. Cell. Biol. 6, 168–182 (1986).

    Article  CAS  Google Scholar 

  5. Padgett, R.W., Hutchison, C.A. III & 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. 16, 739–749 (1988).

    Article  CAS  Google Scholar 

  6. 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. 9, 41–55 (1992).

    CAS  PubMed  Google Scholar 

  7. Naas, T.P. et al. An actively-retrotransposing, novel subfamily of mouse L1 elements. EMBO J. 17, 590– 597 (1998).

    Article  CAS  Google Scholar 

  8. Adey, N.B. et al. Rodent L1 evolution has been driven by a single dominant lineage that has repeatedly acquired new transcriptional regulatory sequences . Mol. Biol. Evol. 11, 778– 789 (1994).

    CAS  PubMed  Google Scholar 

  9. Schichman, S.A., Severynse, D.M., Edgell, M.H. & Hutchison, C.A. III. Strand-specific LINE-1 transcription in mouse F9 cells originates from the youngest phylogenetic subgroup of LINE-1 elements. J. Mol. Biol. 224, 559– 574 (1992).

    Article  CAS  Google Scholar 

  10. Wincker, P., Jubier-Maurin, V. & Roizes, G. Unrelated sequences at the 5' end of mouse LINE-1 repeated elements define two distinct subfamilies. Nucleic Acids Res. 15, 8593–8606 (1987).

    Article  CAS  Google Scholar 

  11. Shehee, W.R. et al. Determination of a functional ancestral sequence and definition of the 5' end of A-type mouse L1 elements. J. Mol. Biol. 196, 757–767 (1987).

    Article  CAS  Google Scholar 

  12. Kingsmore, S.F. et al. Glycine receptor ß subunit gene mutation in spastic mouse associated with LINE-1 element insertion. Nature Genet. 7, 136–142 (1994).

    Article  CAS  Google Scholar 

  13. Mulhardt, C. et al. The spastic mouse: aberrant splicing of glycine receptor ß subunit mRNA caused by intronic insertion of L1 element. Neuron 13, 1003–1015 (1994).

    Article  CAS  Google Scholar 

  14. Takahara, T. et al. Dysfunction of the Orleans reeler gene arising from exon skipping due to transposition of a full-length copy of an active L1 sequence into the skipped exon. Hum. Mol. Genet. 5, 989–993 (1996).

    Article  CAS  Google Scholar 

  15. Saxton, J.A. & Martin, S.L. Recombination between subtypes creates a mosaic lineage of LINE-1 that is expressed and actively-retrotransposing in the mouse genome. J. Mol. Biol. 280, 611–622 (1998).

    Article  CAS  Google Scholar 

  16. DeBerardinis, R.J. Retrotransposition and Evolution of Mammalian L1 Elements. PhD Thesis, Univ. Penn. (1998).

  17. Moran, J.V. et al. High frequency retrotransposition in cultured mammalian cells. Cell 87, 917–927 (1996).

    Article  CAS  Google Scholar 

  18. Skowronski, J., Fanning, T.G. & Singer, M.F. Unit-length LINE-1 transcripts in human teratocarcinoma cells. Mol. Cell. Biol. 8, 1385– 1397 (1988).

    Article  CAS  Google Scholar 

  19. Sassaman, D.M. et al. Many human L1 elements are capable of retrotransposition. Nature Genet. 16, 37–43 (1997).

    Article  CAS  Google Scholar 

  20. She, J.X., Bonhomme, F., Boursot, P., Thaler, L. & Catzeflis, F. Molecular phylogenies in the genus Mus: comparative analysis of electrophoretic, scnDNS, and mtDNA RFLP data. Biol. J. Linnean Soc. 41, 83– 103 (1990).

    Article  Google Scholar 

  21. Sambrook, J., Fritsch, E.F. & Maniatis, T. Molecular Cloning: A Laboratory Manual (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York, 1989).

  22. Thaler, L. Origin and evolution of mice: an appraisal of fossil evidence and morphological traits. Curr. Top. Microbiol. Immunol. 127, 3–11 (1986).

    CAS  PubMed  Google Scholar 

  23. Lundrigan, B.L. & Tucker, P.K. Tracing paternal ancestry in mice, using the Y-linked, sex-determining locus, Sry. Mol. Biol. Evol. 11, 483–492 (1994).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank K. Kaestner for providing the E14TG2a genomic library, C. Hutchison and M. Edgell for providing an A-monomer probe and D. Gasser, W. Silvers and B. Taylor for helpful discussions. We also thank J. Moran, E. Luning Prak and B. Dombroski for critical reading of the manuscript, and the DNA sequencing core at the University of Pennsylvania School of Medicine. H.H.K. was supported by an NIH grant.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Haig H. Kazazian Jr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

DeBerardinis, R., Goodier, J., Ostertag, E. et al. Rapid amplification of a retrotransposon subfamily is evolving the mouse genome. Nat Genet 20, 288–290 (1998). https://doi.org/10.1038/3104

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/3104

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing