Hartl D L, Moriyama E N, Sawyer S A
Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138.
Genetics. 1994 Sep;138(1):227-34. doi: 10.1093/genetics/138.1.227.
The patterns of nonrandom usage of synonymous codons (codon bias) in enteric bacteria were analyzed. Poisson random field (PRF) theory was used to derive the expected distribution of frequencies of nucleotides differing from the ancestral state at aligned sites in a set of DNA sequences. This distribution was applied to synonymous nucleotide polymorphisms and amino acid polymorphisms in the gnd and putP genes of Escherichia coli. For the gnd gene, the average intensity of selection against disfavored synonymous codons was estimated as approximately 7.3 x 10(-9); this value is significantly smaller than the estimated selection intensity against selectively disfavored amino acids in observed polymorphisms (2.0 x 10(-8)), but it is approximately of the same order of magnitude. The selection coefficients for optimal synonymous codons estimated from PRF theory were consistent with independent estimates based on codon usage for threonine and glycine. Across 118 genes in E. coli and Salmonella typhimurium, the distribution of estimated selection coefficients, expressed as multiples of the effective population size, has a mean and standard deviation of 0.5 +/- 0.4. No significant differences were found in the degree of codon bias between conserved positions and replacement positions, suggesting that translational misincorporation is not an important selective constraint among synonymous polymorphic codons in enteric bacteria. However, across the first 100 codons of the genes, conserved amino acids with identical codons have significantly greater codon bias than that of either synonymous or nonidentical codons, suggesting that there are unique selective constraints, perhaps including mRNA secondary structures, in this part of the coding region.
分析了肠道细菌中同义密码子的非随机使用模式（密码子偏好）。利用泊松随机场（PRF）理论推导了一组DNA序列中比对位点上与祖先状态不同的核苷酸频率的预期分布。将该分布应用于大肠杆菌gnd和putP基因中的同义核苷酸多态性和氨基酸多态性。对于gnd基因，针对不利同义密码子的选择平均强度估计约为7.3×10⁻⁹；该值明显小于观察到的多态性中针对不利氨基酸的估计选择强度（2.0×10⁻⁸），但大致处于相同数量级。从PRF理论估计的最佳同义密码子的选择系数与基于苏氨酸和甘氨酸密码子使用的独立估计一致。在大肠杆菌和鼠伤寒沙门氏菌的118个基因中，以有效种群大小的倍数表示的估计选择系数分布的均值和标准差为0.5±0.4。在保守位点和替换位点之间未发现密码子偏好程度的显著差异，这表明翻译错误掺入在肠道细菌的同义多态密码子中不是一个重要的选择限制。然而，在基因的前100个密码子中，具有相同密码子的保守氨基酸的密码子偏好明显大于同义或不同密码子，这表明在编码区的这一部分存在独特的选择限制，可能包括mRNA二级结构。
