Tzeng Yun-Huei, Pan Runsun, Li Wen-Hsiung
Department of Ecology and Evolution, University of Chicago, USA.
Mol Biol Evol. 2004 Dec;21(12):2290-8. doi: 10.1093/molbev/msh242. Epub 2004 Aug 25.
Three frequently used methods for estimating the synonymous and nonsynonymous substitution rates (Ks and Ka) were evaluated and compared for their accuracies; these methods are denoted by LWL85, LPB93, and GY94, respectively. For this purpose, we used a codon-evolution model to obtain the expected Ka and Ks values for the above three methods and compared the values with those obtained by the three methods. We also proposed some modifications of LWL85 and LPB93 to increase their accuracies. Our computer simulations under the codon-evolution model showed that for sequences < or =300 codons, the performance of GY94 may not be reliable. For longer sequences, GY94 is more accurate for estimating the Ka/Ks ratio than the modified LPB93 and LWL85 in the majority of the cases studied. This is particularly so when k > or = 3, which is the transition/transversion (mutation) rate ratio. However, when k is approximately 2 and when the sequence divergence is relatively large, the modified LWL85 performed better than GY94 and the modified LPB93. The inferiority of LPB93 to LWL85 is surprising because LPB93 was intended to improve LWL85. Also, it has been thought that the codon-based method of GY94 is better than the heuristic method of LWL85, but our simulation results showed that in many cases, the opposite was true, even though our simulation was based on the codon-evolution model.
我们评估并比较了三种常用的估计同义替换率和非同义替换率（Ks和Ka）的方法的准确性；这三种方法分别用LWL85、LPB93和GY94表示。为此，我们使用密码子进化模型来获得上述三种方法的预期Ka和Ks值，并将这些值与三种方法得到的值进行比较。我们还对LWL85和LPB93提出了一些改进措施以提高其准确性。我们在密码子进化模型下进行的计算机模拟表明，对于长度小于或等于300个密码子的序列，GY94的性能可能不可靠。对于更长的序列，在大多数研究案例中,GY94在估计Ka/Ks比率方面比改进后的LPB93和LWL85更准确。当k大于或等于3（即转换/颠换（突变）率比率）时尤其如此。然而，当k约为2且序列分歧相对较大时，改进后的LWL85比GY94和改进后的LPB93表现更好。LPB93比LWL85差，这很令人惊讶，因为LPB93旨在改进LWL85。此外，人们一直认为基于密码子的GY94方法比LWL85的启发式方法更好，但我们的模拟结果表明，在许多情况下，情况恰恰相反，尽管我们的模拟是基于密码子进化模型的。
