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Proliferation of Endogenous Retroviruses in the Early Stages of a Host Germ Line Invasion

Yasuko Ishida,*,1 Kai Zhao,1 Alex D. Greenwood,2 and Alfred L. Roca*,1,3

1Department of Animal Sciences, University of Illinois at Urbana-Champaign

2Department of Wildlife Diseases, Leibniz Institute for Zoo and Wildlife Research, Berlin, Germany

3The Institute for Genomic Biology, University of Illinois at Urbana-Champaign

*Corresponding author: E-mail: ; . Associate editor: Emma Teeling


ABSTRACT

Endogenous retroviruses (ERVs) comprise 8% of the human genome and are common in all vertebrate genomes. The only retrovirus known to be currently transitioning from exogenous to endogenous form is the koala retrovirus (KoRV), making koalas (Phascolarctos cinereus) ideal for examining the early stages of retroviral endogenization. To distinguish endogenous from exogenous KoRV proviruses, we isolated koala genomic regions flanking KoRV integration sites. In three wild southern Australian koalas, there were fewer KoRV loci than in three captive Queensland koalas, consistent with reports that southern Australian koalas carry fewer KoRVs. Of 39 distinct KoRV proviral loci examined in a sire– dam–progeny triad, all proved to be vertically transmitted and endogenous; none was exogenous. Of the 39 endogenous KoRVs (enKoRVs), only one was present in the genomes of both the sire and the dam, suggesting that, at this early stage in the retroviral invasion of a host germ line, very large numbers of ERVs have proliferated at very low frequencies in the koala population. Sequence divergence between the 50- and 3 0-long terminal repeats (LTRs) of aproviruscan be used as a molecular clock. Within each of ten enKoRVs, the 50-LTR sequence was identical to the 30-LTR sequence, suggesting a maximum age for enKoRV invasion of the koala germ line of approximately 22,200–49,900 years ago, although a much younger age is possible. Across the ten proviruses, seven LTR haplotypes were detected, indicating that at least seven different retroviral sequences had entered the koala germ line. Key words: insertional polymorphisms, koala, koala retrovirus, long terminal repeats, sire–dam–progeny triad.

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