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Allelic Variation of HERV-K(HML-2) Endogenous Retroviral Elements in Human Populations

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Abstract

Human endogenous retroviruses (HERVs) are the remnants of ancient germ cell infection by exogenous retroviruses and occupy up to 8% of the human genome. It has been suggested that HERV sequences have contributed to primate evolution by regulating the expression of cellular genes and mediating chromosome rearrangements. After integration ∼28 million years ago, members of the HERV-K (HML-2) family have continued to amplify and recombine. To investigate the utility of HML-2 polymorphisms as markers for the study of more recent human evolution, we compiled a list of the structure and integration sites of sequences that are unique to humans and screened each insertion for polymorphism within the human genome databases. Of the total of 74 HML-2 sequences, 18 corresponded to complete or near-complete proviruses, 49 were solitary long terminal repeats (LTRs), 6 were incomplete LTRs, and 1 was a SVA retrotransposon. A number of different allelic configurations were identified including the alternation of a provirus and solitary LTR. We developed polymerase chain reaction-based assays for seven HML-2 loci and screened 109 human DNA samples from Africa, Europe, Asia, and Southeast Asia. Our results indicate that the diversity of HML-2 elements is higher in African than non-African populations, with population differentiation values ranging from 0.6 to 9.8%. These findings denote a recent expansion from Africa. We compare the phylogenetic relationships of HML-2 sequences that are unique to humans and consider whether these elements have played a role in the remodeling of the hominid genome.

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Acknowledgment

We would like to thank Alastair Macdonald, Rochelle Bleeker, Anna Meredith, Benjamin Searle, and Sonia Lee for their help with sample collection.

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  1. Center for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, Scotland, EH9 1QH, UK

    Catriona Macfarlane & Peter Simmonds

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  1. Catriona Macfarlane
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  2. Peter Simmonds
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Correspondence to Catriona Macfarlane.

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Reviewing Editor: Dr. Wen-Hsiung Li

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Macfarlane, C., Simmonds, P. Allelic Variation of HERV-K(HML-2) Endogenous Retroviral Elements in Human Populations. J Mol Evol 59, 642–656 (2004). https://doi.org/10.1007/s00239-004-2656-1

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