Evolutionary interplay between structure, energy and epistasis in the coat protein of the fX174 phage family

R.A. Fernandes Redondo, H. Vladar, T. Włodarski, J.P. Bollback, Journal of the Royal Society Interface 14 (2017).

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Journal Article | Published | English
Abstract
Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the fX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima.
Publishing Year
Date Published
2017-01-04
Journal Title
Journal of the Royal Society Interface
Volume
14
Issue
126
Article Number
20160139
ISSN
IST-REx-ID

Cite this

Fernandes Redondo RA, Vladar H, Włodarski T, Bollback JP. Evolutionary interplay between structure, energy and epistasis in the coat protein of the fX174 phage family. Journal of the Royal Society Interface. 2017;14(126). doi:10.1098/rsif.2016.0139
Fernandes Redondo, R. A., Vladar, H., Włodarski, T., & Bollback, J. P. (2017). Evolutionary interplay between structure, energy and epistasis in the coat protein of the fX174 phage family. Journal of the Royal Society Interface, 14(126). https://doi.org/10.1098/rsif.2016.0139
Fernandes Redondo, Rodrigo A, Harold Vladar, Tomasz Włodarski, and Jonathan P Bollback. “Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the FX174 Phage Family.” Journal of the Royal Society Interface 14, no. 126 (2017). https://doi.org/10.1098/rsif.2016.0139.
R. A. Fernandes Redondo, H. Vladar, T. Włodarski, and J. P. Bollback, “Evolutionary interplay between structure, energy and epistasis in the coat protein of the fX174 phage family,” Journal of the Royal Society Interface, vol. 14, no. 126, 2017.
Fernandes Redondo RA, Vladar H, Włodarski T, Bollback JP. 2017. Evolutionary interplay between structure, energy and epistasis in the coat protein of the fX174 phage family. Journal of the Royal Society Interface. 14(126).
Fernandes Redondo, Rodrigo A., et al. “Evolutionary Interplay between Structure, Energy and Epistasis in the Coat Protein of the FX174 Phage Family.” Journal of the Royal Society Interface, vol. 14, no. 126, 20160139, Royal Society of London, 2017, doi:10.1098/rsif.2016.0139.
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