Poxviruses capture host genes by LINE-1 retrotransposition

  1. Sarah M Fixsen
  2. Kelsey R Cone
  3. Stephen A Goldstein
  4. Thomas A Sasani
  5. Aaron R Quinlan
  6. Stefan Rothenburg
  7. Nels C Elde  Is a corresponding author
  1. University of Utah, United States
  2. University of California, Davis, United States

Abstract

Horizontal gene transfer (HGT) provides a major source of genetic variation. Many viruses, including poxviruses, encode genes with crucial functions directly gained by gene transfer from hosts. The mechanism of transfer to poxvirus genomes is unknown. Using genome analysis and experimental screens of infected cells, we discovered a central role for Long Interspersed Nuclear Element-1 (LINE-1) retrotransposition in HGT to virus genomes. The process recapitulates processed pseudogene generation, but with host messenger RNA directed into virus genomes. Intriguingly, hallmark features of retrotransposition appear to favor virus adaption through rapid duplication of captured host genes on arrival. Our study reveals a previously unrecognized conduit of genetic traffic with fundamental implications for the evolution of many virus classes and their hosts.

Data availability

Sequencing data have been deposited in the NCBI SRA database under project code PRJNA614958.All data generated or analyses during this study are included in the manuscript and supplemental files.

The following data sets were generated

Article and author information

Author details

  1. Sarah M Fixsen

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  2. Kelsey R Cone

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4547-7174
  3. Stephen A Goldstein

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  4. Thomas A Sasani

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2317-1374
  5. Aaron R Quinlan

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    Competing interests
    No competing interests declared.
  6. Stefan Rothenburg

    Department of Medical Microbiology and Immunology, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2525-8230
  7. Nels C Elde

    Department of Human Genetics, University of Utah, Salt Lake City, United States
    For correspondence
    nelde@genetics.utah.edu
    Competing interests
    Nels C Elde, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0426-1377

Funding

National Institutes of Health (R35GM134936)

  • Nels C Elde

National Institutes of Health (T32GM007464)

  • Sarah M Fixsen
  • Thomas A Sasani

National Institutes of Health (T32AI055434)

  • Kelsey R Cone

Burroughs Wellcome Fund (1015462)

  • Nels C Elde

University of Utah (HA and Edna Benning Presidential Endowed Chair)

  • Nels C Elde

National Institutes of Health (R01AI146915)

  • Stefan Rothenburg

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Karla Kirkegaard, Stanford University School of Medicine, United States

Publication history

  1. Received: September 22, 2020
  2. Preprint posted: October 27, 2020 (view preprint)
  3. Accepted: September 6, 2022
  4. Accepted Manuscript published: September 7, 2022 (version 1)

Copyright

© 2022, Fixsen et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 467
    Page views
  • 215
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Sarah M Fixsen
  2. Kelsey R Cone
  3. Stephen A Goldstein
  4. Thomas A Sasani
  5. Aaron R Quinlan
  6. Stefan Rothenburg
  7. Nels C Elde
(2022)
Poxviruses capture host genes by LINE-1 retrotransposition
eLife 11:e63332.
https://doi.org/10.7554/eLife.63332

Further reading

    1. Epidemiology and Global Health
    2. Evolutionary Biology
    Erin Brintnell, Art Poon
    Insight

    Combining clinical and genetic data can improve the effectiveness of virus tracking with the aim of reducing the number of HIV cases by 2030.

    1. Evolutionary Biology
    Julian M Wagner, C Jaco Klok ... Jon F Harrison
    Research Article Updated

    The scaling of respiratory structures has been hypothesized to be a major driving factor in the evolution of many aspects of animal physiology. Here, we provide the first assessment of the scaling of the spiracles in insects using 10 scarab beetle species differing 180× in mass, including some of the most massive extant insect species. Using X-ray microtomography, we measured the cross-sectional area and depth of all eight spiracles, enabling the calculation of their diffusive and advective capacities. Each of these metrics scaled with geometric isometry. Because diffusive capacities scale with lower slopes than metabolic rates, the largest beetles measured require 10-fold higher PO2 gradients across the spiracles to sustain metabolism by diffusion compared to the smallest species. Large beetles can exchange sufficient oxygen for resting metabolism by diffusion across the spiracles, but not during flight. In contrast, spiracular advective capacities scale similarly or more steeply than metabolic rates, so spiracular advective capacities should match or exceed respiratory demands in the largest beetles. These data illustrate a general principle of gas exchange: scaling of respiratory transport structures with geometric isometry diminishes the potential for diffusive gas exchange but enhances advective capacities; combining such structural scaling with muscle-driven ventilation allows larger animals to achieve high metabolic rates when active.