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.
- 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
Principles of dengue virus evolvability derived from genotype-fitness maps in human and mosquito cells. https://doi.org/10.1101/2020.02.05.936195 Dolan, PT and Taguwa, S and Aguilar Rangel, M and Acevedo, A and Hagai, T and Andino, R and Frydman, J. (2020). Principles of dengue virus evolvability derived from genotype-fitness maps in human and mosquito cells.doi:10.1101/2020.02.05.936195.
- Patrick T Dolan
- Raul Andino
- Judith Frydman
- Shuhei Taguwa
- Shuhei Taguwa
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Rafael Sanjuan, Universitat de Valencia
© 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.
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.
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.