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Retroviral integrations contribute to elevated host cancer rates during germline invasion

Author

Listed:
  • Gayle K. McEwen

    (Leibniz Institute for Zoo and Wildlife Research)

  • David E. Alquezar-Planas

    (Leibniz Institute for Zoo and Wildlife Research
    Australian Museum)

  • Anisha Dayaram

    (Leibniz Institute for Zoo and Wildlife Research
    Charité-Universitätsmedizin Berlin)

  • Amber Gillett

    (Australia Zoo Wildlife Hospital)

  • Rachael Tarlinton

    (University of Nottingham)

  • Nigel Mongan

    (University of Nottingham)

  • Keith J. Chappell

    (University of Queensland)

  • Joerg Henning

    (University of Queensland)

  • Milton Tan

    (University of Illinois at Urbana–Champaign)

  • Peter Timms

    (University of the Sunshine Coast)

  • Paul R. Young

    (University of Queensland)

  • Alfred L. Roca

    (University of Illinois at Urbana–Champaign)

  • Alex D. Greenwood

    (Leibniz Institute for Zoo and Wildlife Research
    Freie Universität)

Abstract

Repeated retroviral infections of vertebrate germlines have made endogenous retroviruses ubiquitous features of mammalian genomes. However, millions of years of evolution obscure many of the immediate repercussions of retroviral endogenisation on host health. Here we examine retroviral endogenisation during its earliest stages in the koala (Phascolarctos cinereus), a species undergoing germline invasion by koala retrovirus (KoRV) and affected by high cancer prevalence. We characterise KoRV integration sites (IS) in tumour and healthy tissues from 10 koalas, detecting 1002 unique IS, with hotspots of integration occurring in the vicinity of known cancer genes. We find that tumours accumulate novel IS, with proximate genes over-represented for cancer associations. We detect dysregulation of genes containing IS and identify a highly-expressed transduced oncogene. Our data provide insights into the tremendous mutational load suffered by the host during active retroviral germline invasion, a process repeatedly experienced and overcome during the evolution of vertebrate lineages.

Suggested Citation

  • Gayle K. McEwen & David E. Alquezar-Planas & Anisha Dayaram & Amber Gillett & Rachael Tarlinton & Nigel Mongan & Keith J. Chappell & Joerg Henning & Milton Tan & Peter Timms & Paul R. Young & Alfred L, 2021. "Retroviral integrations contribute to elevated host cancer rates during germline invasion," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21612-7
    DOI: 10.1038/s41467-021-21612-7
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    Cited by:

    1. Jianhua Wang & Guan-Zhu Han, 2023. "Genome mining shows that retroviruses are pervasively invading vertebrate genomes," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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