Bielawski J P, Dunn K A, Yang Z
Department of Biology, University College London, London NW1 2HE, United Kingdom.
Genetics. 2000 Nov;156(3):1299-308. doi: 10.1093/genetics/156.3.1299.
Rates and patterns of synonymous and nonsynonymous substitutions have important implications for the origin and maintenance of mammalian isochores and the effectiveness of selection at synonymous sites. Previous studies of mammalian nuclear genes largely employed approximate methods to estimate rates of nonsynonymous and synonymous substitutions. Because these methods did not account for major features of DNA sequence evolution such as transition/transversion rate bias and unequal codon usage, they might not have produced reliable results. To evaluate the impact of the estimation method, we analyzed a sample of 82 nuclear genes from the mammalian orders Artiodactyla, Primates, and Rodentia using both approximate and maximum-likelihood methods. Maximum-likelihood analysis indicated that synonymous substitution rates were positively correlated with GC content at the third codon positions, but independent of nonsynonymous substitution rates. Approximate methods, however, indicated that synonymous substitution rates were independent of GC content at the third codon positions, but were positively correlated with nonsynonymous rates. Failure to properly account for transition/transversion rate bias and unequal codon usage appears to have caused substantial biases in approximate estimates of substitution rates.
同义替换和非同义替换的速率及模式对于哺乳动物等染色体的起源和维持以及同义位点选择的有效性具有重要意义。先前对哺乳动物核基因的研究大多采用近似方法来估计非同义替换和同义替换的速率。由于这些方法没有考虑DNA序列进化的主要特征，如转换/颠换率偏差和密码子使用不均衡，它们可能没有得出可靠的结果。为了评估估计方法的影响，我们使用近似方法和最大似然法分析了来自偶蹄目、灵长目和啮齿目哺乳动物的82个核基因样本。最大似然分析表明，同义替换率与第三密码子位置的GC含量呈正相关，但与非同义替换率无关。然而，近似方法表明，同义替换率与第三密码子位置的GC含量无关，但与非同义替换率呈正相关。未能正确考虑转换/颠换率偏差和密码子使用不均衡似乎在替换率的近似估计中造成了重大偏差。
