Skip to main content

Thank you for visiting 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.

Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution


Human endogenous retroviruses (HERVs), which are remnants of past retroviral infections of the germline cells of our ancestors1, make up as much as 8% of the human genome and may even outnumber genes2,3. Most HERVs seem to have entered the genome between 10 and 50 million years ago, and they comprise over 200 distinct groups and subgroups1,4. Although repeated sequence elements such as HERVs have the potential to lead to chromosomal rearrangement through homologous recombination between distant loci, evidence for the generality of this process is lacking. To gain insight into the expansion of these elements in the genome during the course of primate evolution, we have identified 23 new members of the HERV-K (HML-2) group, which is thought to contain the most recently active members. Here we show, by phylogenetic and sequence analysis, that at least 16% of these elements have undergone apparent rearrangements that may have resulted in large-scale deletions, duplications and chromosome reshuffling during the evolution of the human genome.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: Example of the synthesis and integration of a HERV-K provirus into a repetitive element.
Figure 2: Neighbor-joining tree containing the 5′ and 3′ LTRs of all full-length HERV-K elements identified in the human genome sequence.


  1. Boeke, J.D. & Stoye, J.P. in Retroviruses (eds Coffin, J.M., Hughes, S.H. & Varmus, H.) 343–436 (Cold Spring Harbor Laboratory Press, Plainview, NY, 1997).

    Google Scholar 

  2. Lander, E.S. et al. Initial sequencing and analysis of the human genome. Nature 409, 860–921 (2001).

    CAS  Article  Google Scholar 

  3. Venter, J.C. et al. The sequence of the human genome. Science 291, 1304–1351 (2001).

    CAS  Article  Google Scholar 

  4. Jurka, J. Repbase update: a database and an electronic journal of repetitive elements. Trends Genet. 16, 418–420 (2000).

    CAS  Article  Google Scholar 

  5. Barbulescu, M. et al. Many human endogenous retrovirus K (HERV-K) proviruses are unique to humans. Curr. Biol. 9, 861–868 (1999).

    CAS  Article  Google Scholar 

  6. Sugimoto, J. et al. Transcriptionally active herv-k genes: identification, isolation, and chromosomal mapping. Genomics 72, 137–144 (2001).

    CAS  Article  Google Scholar 

  7. Ono, M. Molecular cloning and long terminal repeat sequences of human endogenous retrovirus genes related to types A and B retrovirus genes. J. Virol. 58, 937–944 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Blanco, P. et al. Divergent outcomes of intrachromosomal recombination on the human Y chromosome: male infertility and recurrent polymorphism. J. Med. Genet. 37, 752–758 (2000).

    CAS  Article  Google Scholar 

  9. Rearden, A., Magnet, A., Kudo, S. & Fukuda, M. Glycophorin B and glycophorin E genes arose from the glycophorin A ancestral gene via two duplications during primate evolution. J. Biol. Chem. 268, 2260–2267 (1993).

    CAS  PubMed  Google Scholar 

  10. Schwartz, A. et al. Reconstructing hominid Y evolution: X-homologous block, created by X–Y transposition, was disrupted by Yp inversion through LINE–LINE recombination. Hum. Mol. Genet. 7, 1–11 (1998).

    CAS  Article  Google Scholar 

  11. Johnson, W.E. & Coffin, J.M. Constructing primate phylogenies from ancient retrovirus sequences. Proc. Natl Acad. Sci. USA 96, 10254–10260 (1999).

    CAS  Article  Google Scholar 

  12. Kamp, C., Hirschmann, P., Voss, H., Huellen, K. & Vogt, P.H. Two long homologous retroviral sequence blocks in proximal Yq11 cause AZFa microdeletions as a result of intrachromosomal recombination events. Hum. Mol. Genet. 9, 2563–2572 (2000).

    CAS  Article  Google Scholar 

  13. Kulski, J.K., Gaudieri, S., Martin, A. & Dawkins, R.L. Coevolution of PERB11 (MIC) and HLA class I genes with HERV-16 and retroelements by extended genomic duplication. J. Mol. Evol. 49, 84–97 (1999).

    CAS  Article  Google Scholar 

  14. Costas, J. Evolutionary dynamics of the human endogenous retrovirus family herv-k inferred from full-length proviral genomes. J. Mol. Evol. 53, 237–243 (2001).

    CAS  Article  Google Scholar 

  15. Reus, K. et al. HERV-K(OLD): ancestor sequences of the human endogenous retrovirus family HERV-K(HML-2). J. Virol. 75, 8917–8926 (2001).

    CAS  Article  Google Scholar 

  16. Yoder, A.D. & Yang, Z. Estimation of primate speciation dates using local molecular clocks. Mol. Biol. Evol. 17, 1081–1090 (2000).

    CAS  Article  Google Scholar 

Download references


We thank N. Rosenberg for helpful advice. This work was supported by research grants R35 CA 44385 and R01 CA 89441 from the National Cancer Institute. J.M.C. was a Research Professor of the American Cancer Society and J.F.H. was supported in part by training grant CA5441 from the National Cancer Institute.

Author information

Authors and Affiliations


Corresponding author

Correspondence to John M. Coffin.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Hughes, J., Coffin, J. Evidence for genomic rearrangements mediated by human endogenous retroviruses during primate evolution. Nat Genet 29, 487–489 (2001).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


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