Dufton M J
Department of Pure and Applied Chemsitry, University of Strathclyde, 295 Cathedral Street, Glasgow, G1 1XL, U.K.
J Theor Biol. 1997 Jul 21;187(2):165-73. doi: 10.1006/jtbi.1997.0443.
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 existence 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.
研究了遗传密码中20种常见氨基酸的同义密码子配额，这些氨基酸可根据其共享的物理化学性质被归为不同的类别。这揭示了在蛋白质进化过程中，密码子的排列对哪些共享性质起到了促进或抑制作用。一个主要的趋势是，同义密码子配额的分配有利于小分子和化学结构简单的残基，而不利于大分子和化学性质突出的残基。在各种可被视为定量表达氨基酸残基“大小和复杂性”的测量方法中（例如侧链体积、体积和分子量），分子量与每种氨基酸的同义密码子配额相关性最高。然而，这种相关性较弱。基于氨基酸相对原子组成专门推导的“大小/复杂性”量表，仅略微提高了相关性。同义密码子配额与蛋白质的一般氨基酸组成之间存在另一种弱相关性，这促使人们研究这种组成与先前考虑的氨基酸性质之间的相关性。同样，相关性最高的是氨基酸分子量和“大小/复杂性”，但在这种情况下，相关性高到足以具有真正的显著性。有人认为，遗传密码中偏向的同义密码子配额旨在确保蛋白质整体维持一定的氨基酸组成，甚至在配额中包括补偿性偏差，以抵消蛋白质功能自然选择过程对这种组成产生的相反影响。正是对这些补偿性偏差的需求，阻止了配额与氨基酸复杂性测量之间的简单相关性。最终结果是，氨基酸在功能蛋白中的分布与其化学复杂性大致成比例，这既可以作为一种将随机基因突变的负面影响降至最低的手段（通过减少蛋白质中更“破坏性”类型侧链出现的机会），也可以作为一种确保最经济地利用生物合成资源的手段。根据这种推理，密码子不是一个“冻结的意外”；它具有普遍适用性，因为它在生物合成成本和蛋白质进化速率方面的生物学回报之间提供了能够实现的最佳折衷方案。
