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Journal of Virology, October 2005, p. 12507-12514, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12507-12514.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Genomewide Screening Reveals High Levels of Insertional Polymorphism in the Human Endogenous Retrovirus Family HERV-K(HML2): Implications for Present-Day Activity{dagger}

Robert Belshaw,1* Anna L. A. Dawson,1 John Woolven-Allen,1,2 Joanna Redding,1 Austin Burt,1 and Michael Tristem1

Department of Biological Sciences, Imperial College, Silwood Park Campus, Ascot, Berks SL5 7PY, United Kingdom,1 Plymouth Marine Laboratory, Prospect Place, The Hoe, Plymouth PL1 3DH, United Kingdom2

Received 27 April 2005/ Accepted 1 July 2005

The published human genome sequence contains many thousands of endogenous retroviruses (HERVs) but all are defective, containing nonsense mutations or major deletions. Only the HERV-K(HML2) family has been active since the divergence of humans and chimpanzees; it contains many members that are human specific, as well as several that are insertionally polymorphic (an inserted element present only in some human individuals). Here we perform a genomewide survey of insertional polymorphism levels in this family by using the published human genome sequence and a diverse sample of 19 humans. We find that there are 113 human-specific HERV-K(HML2) elements in the human genome sequence, 8 of which are insertionally polymorphic (11 if we extrapolate to those within regions of the genome that were not suitable for amplification). The average rate of accumulation since the divergence with chimpanzees is thus approximately 3.8 x 10–4 per haploid genome per generation. Furthermore, we find that the number of polymorphic elements is not significantly different from that predicted by a standard population genetic model that assumes constant activity of the family until the present. This suggests to us that the HERV-K(HML2) family may be active in present-day humans. Active (replication-competent) elements are likely to have inserted very recently and to be present at low allele frequencies, and they may be causing disease in the individuals carrying them. This view of the family from a population perspective rather than a genome perspective will inform the current debate about a possible role of HERV-K(HML2) in human disease.

* Corresponding author. Mailing address: Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, United Kingdom. Phone: 44 (0)1865 281997. Fax: 44 (0)1865 271249. E-mail: robert.belshaw{at}zoo.ox.ac.uk.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, October 2005, p. 12507-12514, Vol. 79, No. 19
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.19.12507-12514.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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