Principles of dengue virus evolvability derived from genotype-fitness maps in human and mosquito cells

  1. Patrick T Dolan
  2. Shuhei Taguwa
  3. Mauricio Aguilar Rangel
  4. Ashley Acevedo
  5. Tzachi Hagai
  6. Raul Andino  Is a corresponding author
  7. Judith Frydman  Is a corresponding author
  1. University of California, San Francisco, United States
  2. Stanford University, United States
  3. Tel Aviv University, Israel

Abstract

Dengue virus (DENV) cycles between mosquito and mammalian hosts. To examine how DENV populations adapt to these different host environments we used serial passage in human and mosquito cell lines and estimated fitness effects for all single-nucleotide variants in these populations using ultra-deep sequencing. This allowed us to determine the contributions of beneficial and deleterious mutations to the collective fitness of the population. Our analysis revealed that the continuous influx of a large burden of deleterious mutations counterbalances the effect of rare, host-specific beneficial mutations to shape the path of adaptation. Beneficial mutations preferentially map to intrinsically disordered domains in the viral proteome and cluster to defined regions in the genome. These phenotypically redundant adaptive alleles may facilitate host-specific DENV adaptation. Importantly, the evolutionary constraints described in our simple system mirror trends observed across DENV and Zika strains, indicating it recapitulates key biophysical and biological constraints shaping long-term viral evolution.

Data availability

- All data has been deposited and is available at the persistent URL: https://purl.stanford.edu/gv159td5450- All code for analysis and figure generation is deposited in GitHub: https://github.com/ptdolan/Dolan_Taguwa_Dengue_2020- Sequencing Data has been deposited as BioProject: PRJNA669406

The following data sets were generated

Article and author information

Author details

  1. Patrick T Dolan

    Microbiology and Immunology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4169-0058
  2. Shuhei Taguwa

    Biology, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Mauricio Aguilar Rangel

    Biology, Stanford University, Stanford, CA, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Ashley Acevedo

    Microbiology and Immunology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Tzachi Hagai

    George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Raul Andino

    Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States
    For correspondence
    raul.andino@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5503-9349
  7. Judith Frydman

    Department of Biology, Stanford University, Stanford, United States
    For correspondence
    jfrydman@stanford.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2302-6943

Funding

National Institutes of Health (AI127447,AI36178,AI091575,F32GM113483)

  • Patrick T Dolan
  • Raul Andino
  • Judith Frydman

Naito Foundation

  • Shuhei Taguwa

Uehara Memorial Foundation

  • Shuhei Taguwa

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

Copyright

© 2021, Dolan 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.

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  1. Patrick T Dolan
  2. Shuhei Taguwa
  3. Mauricio Aguilar Rangel
  4. Ashley Acevedo
  5. Tzachi Hagai
  6. Raul Andino
  7. Judith Frydman
(2021)
Principles of dengue virus evolvability derived from genotype-fitness maps in human and mosquito cells
eLife 10:e61921.
https://doi.org/10.7554/eLife.61921

Share this article

https://doi.org/10.7554/eLife.61921

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