Principles of dengue virus evolvability derived from genotype-fitness maps in human and mosquito cells
- University of California, San Francisco, United States
- Stanford University, United States
- 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
Article and author information
Author details
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
- Rafael Sanjuan, Universitat de Valencia
Publication history
- Received: August 8, 2020
- Accepted: January 24, 2021
- Accepted Manuscript published: January 25, 2021 (version 1)
- 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.
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