Synonymous and nonsynonymous rate variation in nuclear genes of mammals

Synonymous and nonsynonymous rate variation in nuclear genes of mammals
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DOI:
10.1007/pl00006320
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发表时间:
1998-04-01
影响因子:
3.9
通讯作者:
Nielsen, R
Nielsen, R
中科院分区:
生物学3区
文献类型:
--
作者:
Yang, ZH;Nielsen, R

文献摘要

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采用最大似然方法估计了灵长类动物、偶蹄动物和啮齿类动物的48个核基因的同义和非同义替换率,并假设了密码子替换模型,该模型考虑了遗传密码子结构、过渡/翻转偏倚和密码子位置的基频偏倚。应用似然比测试来测试分支(进化谱系)之间非同义与同义比率的稳定性。结果发现,在检查的48个核位点中,有22个核位点的非同义/同义比率在树的分支之间变化显著。这一结果提供了强有力的证据,反对严格中立的分子进化模型。我们对同义和非同义率的似然估计与以前从近似两两序列比较中获得的结果有很大不同,通过对几个基因的数据进行详细分析,探讨了方法之间的差异。迁移/翻转率偏差和密码子频率偏差对同义和非同义率的估计有显著影响,近似方法不能充分考虑这些因素。似然方法更可取,甚至对于成对序列比较也是如此,因为关于突变和替代过程的更现实的模型可以纳入分析。
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.