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.

Reviewing Editor

  1. Rafael Sanjuan, Universitat de Valencia

Publication history

  1. Received: August 8, 2020
  2. Accepted: January 24, 2021
  3. Accepted Manuscript published: January 25, 2021 (version 1)
  4. Version of Record published: February 12, 2021 (version 2)

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.

Metrics

  • 2,001
    Page views
  • 295
    Downloads
  • 5
    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. 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
  1. Further reading

Further reading

    1. Evolutionary Biology
    Thodoris Argyriou et al.
    Research Article

    The actinopterygian crown group (comprising all living ray-finned fishes) originated by the end of the Carboniferous. However, most late Paleozoic taxa are stem actinopterygians, and broadly resemble stratigraphically older taxa. The early Permian †Brachydegma caelatum is notable for its three-dimensional preservation and past phylogenetic interpretations as a nested member of the neopterygian crown. Here, we use computed microtomography to redescribe †Brachydegma, uncovering an unanticipated combination of primitive (e.g., aortic canal; immobile maxilla) and derived (e.g., differentiated occipital ossifications; posterior stem of parasphenoid; two accessory hyoidean ossifications; double jaw joint) dermal and endoskeletal features relative to most other Paleozoic actinopterygians. Some of these features were previously thought to be restricted to the neopterygian crown. The precise phylogenetic position of †Brachydegma is unclear, with placements either on the polypterid stem, or as an early-diverging stem neopterygian. However, our analyses decisively reject previous placements of †Brachydegma in the neopterygian crown. Critically, we demonstrate that key-endoskeletal components of the hyoid portion of the suspensorium of crown neopterygians appeared deeper in the tree than previously thought.

    1. Evolutionary Biology
    Jia Jia et al.
    Research Article

    Ecological preferences and life history strategies have enormous impacts on the evolution and phenotypic diversity of salamanders, but the yet established reliable ecological indicators from bony skeletons hinder investigations into the paleobiology of early salamanders. Here we statistically demonstrate, by using time-calibrated cladograms and geometric morphometric analysis on 71 specimens in 36 species, that both the shape of the palate and many non-shape covariates particularly associated with vomerine teeth are ecologically informative in early stem- and basal crown-group salamanders. Disparity patterns within the morphospace of the palate in ecological preferences, life history strategies and taxonomic affiliations were analyzed in detail, and evolutionary rates and ancestral states of the palate were reconstructed. Our results show that the palate is heavily impacted by convergence constrained by feeding mechanisms and also exhibits clear stepwise evolutionary patterns with alternative phenotypic configurations to cope with similar functional demand. Salamanders are diversified ecologically before the Middle Jurassic and achieved all their present ecological preferences in the Early Cretaceous. Our results reveal that the last common ancestor of all salamanders shares with other modern amphibians a unified biphasic ecological preference, and metamorphosis is significant in the expansion of ecomorphospace of the palate in early salamanders.