Genetic code synonym quotas and amino acid complexity: Cutting the cost of proteins?

The synonym quotas within the genetic code for the 20 common amino acids are examined in relation to the ways in which these amino acids can be marshalled into different sets on the basis of shared physico-chemical properties. This reveals which shared properties are encouraged or discouraged during the course of protein evolution by the arrangement of the code. A dominant theme is that the synonym quotas are allocated in favour of small and chemically uncomplicated residues, and to the disadvantage of large and chemically prominent ones. From amongst the various measurements that can be considered to quantitatively express aspects of amino acid residue ''size and complexity'' (e.g. side chain volume, bulkness and formula weight), formula weight has the highest correlation with the synonym quota for each amino acid. However, the correlation is weak. A specially derived ''size/complexity'' scale for the amino acids based on their relative atomic composition improved the correlation only marginally. The existance of another weak correlation between the synonym quotas and the general amino acid composition of proteins prompted an investigation of the correlations between this composition and the previously considered amino acid properties. Again, the highest correlations are with amino acid formula weight and ''size/complexity'', but in this instance the correlations are high enough to be truly significant. It is suggested that the biased synonym quotas in the genetic code are intended to ensure that proteins as a whole maintain a certain amino acid composition, even to the extent that the quotas include compensatory biases to counter opposing influences upon this composition caused by the processes of natural selection for protein function. It is the need for these compensatory biases that prevents a simple correlation between the quotas and measures of amino acid complexity. The final outcome, in which amino acids are deployed in functional proteins in approximate proportion to their chemical complexity may serve both as a means of minimising the negative consequences of random genetic mutation (by reducing the chance appearance of the more ''disruptive'' types of side chain in proteins) and as a means of ensuring the most economic use of biosynthetic resources. According to this reasoning, the code is not a ''frozen accident''; it is universally appropriate because it provides the best compromise that can be achieved between biosynthetic cost and biological return in respect of the rate of protein evolution. (C) 1997 Academic Press Limited.