TY - JOUR
T1 - The Critical Role of Codon Composition on the Translation Efficiency Robustness of the Hepatitis A Virus Capsid
AU - D'Andrea, Lucía
AU - Pérez-Rodríguez, Francisco Javier
AU - De Castellarnau, Montserrat
AU - Guix, Susana
AU - Ribes, Enric
AU - Quer, Josep
AU - Gregori, Josep
AU - Bosch, Albert
AU - Pintó, Rosa M.
N1 - Funding Information:
This work was supported by Spanish Ministry of Economy grants BIO2014-53285-R, BIO2017-83191-R, and PI16/ 00337, the last two cofinanced by the European Regional Development Fund; and by the Generalitat de Catalunya Biotechnology Reference Network. F.J.P., L.dA., and M.dC. were recipients of fellowships from the Spanish Ministry of Science and Innovation; Spanish Ministry of External Affairs and Cooperation; and Spanish Ministry of Economy, respectively.
Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
PY - 2019/7/22
Y1 - 2019/7/22
N2 - Hepatoviruses show an intriguing deviated codon usage, suggesting an evolutionary signature. Abundant and rare codons in the cellular genome are scarce in the human hepatitis A virus (HAV) genome, while intermediately abundant host codons are abundant in the virus. Genotype-phenotype maps, or fitness landscapes, are a means of representing a genotype position in sequence space and uncovering how genotype relates to phenotype and fitness. Using genotype-phenotype maps of the translation efficiency, we have shown the critical role of the HAV capsid codon composition in regulating translation and determining its robustness. Adaptation to an environmental perturbation such as the artificial induction of cellular shutoff - not naturally occurring in HAV infection - involved movements in the sequence space and dramatic changes of the translation efficiency. Capsid rare codons, including abundant and rare codons of the cellular genome, slowed down the translation efficiency in conditions of no cellular shutoff. In contrast, rare capsid codons that are abundant in the cellular genome were efficiently translated in conditions of shutoff. Capsid regions very rich in slowly translated codons adapt to shutoff through sequence space movements from positions with highly robust translation to others with diminished translation robustness. These movements paralleled decreases of the capsid physical and biological robustness, and resulted in the diversification of capsid phenotypes. The deviated codon usage of extant hepatoviruses compared with that of their hosts may suggest the occurrence of a virus ancestor with an optimized codon usage with respect to an unknown ancient host.
AB - Hepatoviruses show an intriguing deviated codon usage, suggesting an evolutionary signature. Abundant and rare codons in the cellular genome are scarce in the human hepatitis A virus (HAV) genome, while intermediately abundant host codons are abundant in the virus. Genotype-phenotype maps, or fitness landscapes, are a means of representing a genotype position in sequence space and uncovering how genotype relates to phenotype and fitness. Using genotype-phenotype maps of the translation efficiency, we have shown the critical role of the HAV capsid codon composition in regulating translation and determining its robustness. Adaptation to an environmental perturbation such as the artificial induction of cellular shutoff - not naturally occurring in HAV infection - involved movements in the sequence space and dramatic changes of the translation efficiency. Capsid rare codons, including abundant and rare codons of the cellular genome, slowed down the translation efficiency in conditions of no cellular shutoff. In contrast, rare capsid codons that are abundant in the cellular genome were efficiently translated in conditions of shutoff. Capsid regions very rich in slowly translated codons adapt to shutoff through sequence space movements from positions with highly robust translation to others with diminished translation robustness. These movements paralleled decreases of the capsid physical and biological robustness, and resulted in the diversification of capsid phenotypes. The deviated codon usage of extant hepatoviruses compared with that of their hosts may suggest the occurrence of a virus ancestor with an optimized codon usage with respect to an unknown ancient host.
KW - Codon usage
KW - Translation efficiency
KW - Sequence space
KW - Fitness landscape
KW - Genotype–phenotype maps
KW - Codon usage
KW - Translation efficiency
KW - Sequence space
KW - Fitness landscape
KW - Genotype–phenotype maps
KW - Codon usage
KW - Translation efficiency
KW - Sequence space
KW - Fitness landscape
KW - Genotype–phenotype maps
UR - http://www.scopus.com/inward/record.url?scp=85071897551&partnerID=8YFLogxK
U2 - 10.1093/gbe/evz146
DO - 10.1093/gbe/evz146
M3 - Article
C2 - 31290967
AN - SCOPUS:85071897551
SN - 1759-6653
VL - 11
SP - 2439
EP - 2456
JO - Genome Biology and Evolution
JF - Genome Biology and Evolution
IS - 9
ER -