Frömmel C, Holzhütter H G
J Mol Evol. 1984;21(3):233-57. doi: 10.1007/BF02102357.
We outline a method for estimating quantitatively the influence of point mutations and selection on the frequencies of codons and amino acids. We show how the mutation rate, i.e., the rate of amino acid replacement due to point mutation, can be affected by the codon usage as well as by the rates of the involved base exchanges. A comparison of the mutation rates calculated from reliable values of codon usage and base exchange probabilities with those that would be expected on the basis of chance reveals a notable suppression of replacements leading to tryptophan, glutamate, lysine, and methionine, and particularly of those leading to the termination codons. If selection constraints are neglected and only mutations are taken into account, the best agreement between expected and observed frequencies of both codons and amino acids is obtained for alpha = 1.13-1.15, where (Formula: see text). The "selection values" of codons and amino acids derived by our method show a pattern that partially deviates from others in the literature. For example, the selection pressure on methionine and cysteine turns out to be much more pronounced than expected if only the discrepancies between their observed and expected occurrences in proteins are considered. To estimate to what extent randomly occurring amino acid replacements are accepted by selection, we constructed an "acceptability matrix" from the well-established matrix of accepted point mutations. On the basis of this matrix "acceptability values" of the amino acids can be defined that correlate with their selection values. We also examine the significance of mutations and selection of amino acids with respect to their physicochemical properties and functions in proteins. The conservatism of amino acid replacements with respect to certain properties such as polarity can be brought about by the mutational process alone, whereas the conservatism with respect to other relevant properties--among them all measures of bulkiness--obviously is the result of additional selectional constraints on the evolution of protein structures.
我们概述了一种定量估计点突变和选择对密码子及氨基酸频率影响的方法。我们展示了突变率，即由于点突变导致的氨基酸替换率，如何受到密码子使用情况以及所涉及碱基交换率的影响。将根据可靠的密码子使用值和碱基交换概率计算出的突变率与基于随机情况预期的突变率进行比较，结果显示导致色氨酸、谷氨酸、赖氨酸和甲硫氨酸的替换，尤其是导致终止密码子的替换受到显著抑制。如果忽略选择限制而仅考虑突变，对于α = 1.13 - 1.15（公式：见正文），密码子和氨基酸的预期频率与观察频率之间能获得最佳拟合。我们的方法得出的密码子和氨基酸的“选择值”呈现出一种模式，部分偏离了文献中的其他模式。例如，如果仅考虑甲硫氨酸和半胱氨酸在蛋白质中的观察到的和预期的出现频率差异，那么对它们的选择压力比预期的要明显得多。为了估计随机发生的氨基酸替换在多大程度上被选择所接受，我们从已确立的接受点突变矩阵构建了一个“可接受性矩阵”。基于这个矩阵，可以定义与氨基酸选择值相关的氨基酸“可接受性值”。我们还研究了氨基酸突变和选择在其物理化学性质及蛋白质功能方面的意义。氨基酸替换在某些性质（如极性）方面的保守性可能仅由突变过程导致，而在其他相关性质（包括所有体积大小的度量）方面的保守性显然是对蛋白质结构进化的额外选择限制的结果。
