The researchers looked deeper into these observations, in hopes of gaining insight into the mechanisms underlying the high evolutionary rate and extraordinary immunologic plasticity of influenza HA. They probed in more detail the precise codons that are used by the virus to encode the influenza HA1 protein. The discriminated between codons on the basis of volatility. Each three-nucleotide codon is related by a single nucleotide change to nine 'mutational neighbours.' Of those nine mutations, some proportion change the codon to a synonymous codon and some change it to a nonsynonymous one, which directs the incorporation of a different amino acid into the protein. More volatile codons are those for which a larger proportion of those nine mutational neighbours encode an amino acid change. The use of particular codons in a gene at a frequency that is disproportionate to their random selection for encoding a chosen amino acid is termed codon bias. Such bias is common and is influenced by many factors, but here the collaborators found strong evidence for codon bias that was particular for and restricted to the amino acids making up the HA1 epitopes. Remarkably, they observed that influenza employs a disproportionate number of volatile codons in its epitope-coding sequences. There was a bias for the use of codons that had the fewest synonymous mutational neighbours. In other words, influenza HA1 appears to have optimized the speed with which it can change amino acids in its epitopes. Amino acid changes can arise from fewer mutational events. The antibody combining regions are optimized to use codons that have a greater likelihood to undergo nonsynonymous single nucleotide substitutions : they are optimized for rapid evolution.
Michael G Cordingley, Viruses: Agents of Evolutionary Invention
evolution, evolved-for-evolvability, influenza, volatile-codons, volatility