Miyata T, Miyazawa S, Yasunaga T
J Mol Evol. 1979 Mar 15;12(3):219-36. doi: 10.1007/BF01732340.
The frequency of amino acid substitutions, relative to the frequency expected by chance, decreases linearly with the increase in physico-chemical differences between amino acid pairs involved in a substitution. This correlation does not apply to abnormal human hemoglobins. Since abnormal hemoglobins mostly reflect the process of mutation rather than selection, the correlation manifest during protein evolution between substitution frequency and physico-chemical difference in amino acids can be attributed to natural selection. Outside of 'abnormal' proteins, the correlation also does not apply to certain regions of proteins characterized by rapid rates of substitution. In these cases again, except for the largest physico-chemical differences between amino acid pairs, the substitution frequencies seem to be independent of the physico-chemical parameters. The limination of the substituents involving the largest physico-chemical differences can once more be attributed to natural selection. For smaller physico-chemical differences, natural selection, if it is operating in the polypeptide regions, must be based on parameters other than those examined.
相对于偶然预期的频率，氨基酸替换的频率随着参与替换的氨基酸对之间物理化学差异的增加而呈线性下降。这种相关性不适用于异常人类血红蛋白。由于异常血红蛋白大多反映突变过程而非选择过程，因此在蛋白质进化过程中替换频率与氨基酸物理化学差异之间表现出的相关性可归因于自然选择。在“异常”蛋白质之外，这种相关性也不适用于以快速替换率为特征的蛋白质的某些区域。在这些情况下，同样除了氨基酸对之间最大的物理化学差异外，替换频率似乎与物理化学参数无关。涉及最大物理化学差异的取代基的消除再次可归因于自然选择。对于较小的物理化学差异，如果自然选择在多肽区域起作用，那么它必须基于所研究参数以外的其他参数。
