Codovirevol
Fidelity during information transfer is essential for life, but it pays to be unfaithful if it provides an evolutionary advantage.
The immune system continuously generates diversity to put up with recurrent pathogen challenges, and many viruses, in its turn, have evolved mechanisms to generate diversity to evade immune restrictions, even at the cost of enduring high mutation rates.
Synonymous codons are not used at random and are not translated with similar efficiency. A large proportion of viruses infecting humans, especially those causing chronic infections, display a poor adaptation to the codon usage preferences of their host. This observation is a paradox, as viral genes completely depend upon the cellular translation machinery for protein synthesis.
We propose here that maladaptation of codon usage preferences in human viruses may have an adaptative value as it reduces protein synthesis, decreases translational fidelity, results in the synthesis of an ill-defined population of viral proteins and provides globally with way to escape immune surveillance.
We propose here that maladaptation of codon usage preferences in human viruses may have an adaptative value as it reduces protein synthesis, decreases translational fidelity, results in the synthesis of an ill-defined population of viral proteins and provides globally with way to escape immune surveillance.
We address the fitness of codon usage bias at the cellular and molecular levels; we apply experimental evolution to analyse genotypic changes by means of next generation sequencing, and monitor phenotypic changes through real-time cell monitoring techniques and comparative proteomics.
Our results will help solve the evolutionary puzzle of codon usage bias for viruses causing chronic infections, and will have implications for the development of mathematical models of virus-host interaction, and for the design of therapeutic vaccines to guide the immune response towards the identification and targeting of the main protein species.
Contributors
Antonin Demange, Marion Picard, Fiona Leblay, Fanni Borveto, Laura Byk, Ignacio Bravo
