Fitch W M
J Mol Evol. 1981;18(1):60-7. doi: 10.1007/BF01733212.
In response to criticism of REH theory (Fitch 1980), Holmquist and Jukes (1981) have mostly avoided the criticism or misunderstood it. Since they themselves state in their response that "Amino acid sequence data alone cannot be used to estimate total nucleotide substitutions," they agree with the criticism. Most of their paper treats the newer theory (here designated as the REHN theory) which attempts to use the nucleotide sequences encoding proteins to better estimate total nucleotide substitutions (Holmquist and Pearl 1980). Since I made no criticism of REHN theory, their comments are frequently beside the point of my original criticism of REH theory. Nevertheless, it is shown here that REHN theory is also unsatisfactory in that: One, the varions are now more clearly defined but in such a way as to preclude the same codon from suffering a nucleotide substitution in more than one evolutionary interval. Two, the set of codons that accepts silent substitutions is identical to the set that accepts amino acid changing nucleotide substitutions. Three, the uncertainty in the REH estimate is considerable in that alternative excellent fits to the same observational data may give alternative REH values that differ significantly even before stochastic variation and selective bias are considered. Four, the fit of their model to data is an irrelevancy where there are zero degrees of freedom.
针对对REH理论的批评（菲奇，1980年），霍尔姆奎斯特和朱克斯（1981年）大多回避了批评或误解了它。由于他们自己在回应中指出“仅氨基酸序列数据不能用于估计总的核苷酸替换数”，他们认同这一批评。他们论文的大部分内容探讨的是更新的理论（这里称为REHN理论），该理论试图利用编码蛋白质的核苷酸序列来更好地估计总的核苷酸替换数（霍尔姆奎斯特和珀尔，1980年）。由于我没有批评REHN理论，他们的评论常常偏离了我最初对REH理论的批评要点。然而，这里表明REHN理论也不令人满意，原因如下：其一，现在对变异体的定义更清晰了，但以这样一种方式，即同一个密码子在多个进化间隔中不能发生核苷酸替换。其二，接受沉默替换的密码子集合与接受改变氨基酸的核苷酸替换的密码子集合相同。其三，REH估计中的不确定性相当大，因为对相同观测数据的其他极佳拟合可能给出不同的REH值，即使在考虑随机变异和选择偏差之前，这些值也可能有显著差异。其四，在自由度为零的情况下，他们的模型与数据的拟合是无关紧要的。
