Yang Z, Nielsen R
Department of Integrative Biology, University of California, Berkeley, 94720-3140, USA.
J Mol Evol. 1998 Apr;46(4):409-18. doi: 10.1007/pl00006320.
A maximum likelihood approach was used to estimate the synonymous and nonsynonymous substitution rates in 48 nuclear genes from primates, artiodactyls, and rodents. A codon-substitution model was assumed, which accounts for the genetic code structure, transition/transversion bias, and base frequency biases at codon positions. Likelihood ratio tests were applied to test the constancy of nonsynonymous to synonymous rate ratios among branches (evolutionary lineages). It is found that at 22 of the 48 nuclear loci examined, the nonsynonymous/synonymous rate ratio varies significantly across branches of the tree. The result provides strong evidence against a strictly neutral model of molecular evolution. Our likelihood estimates of synonymous and nonsynonymous rates differ considerably from previous results obtained from approximate pairwise sequence comparisons. The differences between the methods are explored by detailed analyses of data from several genes. Transition/transversion rate bias and codon frequency biases are found to have significant effects on the estimation of synonymous and nonsynonymous rates, and approximate methods do not adequately account for those factors. The likelihood approach is preferable, even for pairwise sequence comparison, because more realistic models about the mutation and substitution processes can be incorporated in the analysis.
采用最大似然法估计灵长类动物、偶蹄目动物和啮齿动物48个核基因中的同义替换率和非同义替换率。假定了一种密码子替换模型，该模型考虑了遗传密码结构、转换/颠换偏差以及密码子位置的碱基频率偏差。应用似然比检验来检验各分支（进化谱系）间非同义替换率与同义替换率之比的恒定性。结果发现，在所检测的48个核基因座中的22个，非同义/同义率比在树的各分支间有显著差异。该结果为反对严格的分子进化中性模型提供了有力证据。我们对同义替换率和非同义替换率的似然估计与先前通过近似成对序列比较获得的结果有很大差异。通过对几个基因的数据进行详细分析，探讨了这些方法之间的差异。发现转换/颠换率偏差和密码子频率偏差对同义替换率和非同义替换率的估计有显著影响，而近似方法没有充分考虑这些因素。即使对于成对序列比较，似然法也是更可取的，因为在分析中可以纳入关于突变和替换过程的更现实的模型。
