Pan A, Dutta C, Das J
Biophysics Division, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Calcutta 700032, India.
Gene. 1998 Jul 30;215(2):405-13. doi: 10.1016/s0378-1119(98)00257-1.
Biases in the codon usage and base compositions at three codon sites in different genes of A+T-rich Gram-negative bacterium Haemophillus influenzae and G+C-rich Gram-positive bacterium Mycobacterium tuberculosis have been examined to address the following questions: (1) whether the synonymous codon usage in organisms having highly skewed base compositions is totally dictated by the mutational bias as reported previously (Sharp, P.M., Devine, K.M., 1989. Codon usage and gene expression level in Dictyostelium discoideum: highly expressed genes do 'prefer' optimal codons. Nucleic Acids Res. 17, 5029-5039), or is also controlled by translational selection; (2) whether preference of G in the first codon positions by highly expressed genes, as reported in Escherichia coli (Gutierrez, G., Marquez, L., Marin, A., 1996. Preference for guanosine at first codon position in highly expressed Escherichia coli genes. A relationship with translational efficiency. Nucleic Acids Res. 24, 2525-2527), is true in other bacteria; and (3) whether the usage of bases in three codon positions is species-specific. Result presented here show that even in organisms with high mutational bias, translational selection plays an important role in dictating the synonymous codon usage, though the set of optimal codons is chosen in accordance with the mutational pressure. The frequencies of G-starting codons are positively correlated to the level of expression of genes, as estimated by their Codon Adaptation Index (CAI) values, in M. tuberculosis as well as in H. influenzae in spite of having an A+T-rich genome. The present study on the codon preferences of two organisms with oppositely skewed base compositions thus suggests that the preference of G-starting codons by highly expressed genes might be a general feature of bacteria, irrespective of their overall G+C contents. The ranges of variations in the frequencies of individual bases at the first and second codon positions of genes of both H. influenzae and M. tuberculosis are similar to those of E. coli, implying that though the composition of all three codon positions is governed by a selection-mutation balance, the mutational pressure has little influence in the choice of bases at the first two codon positions, even in organisms with highly biased base compositions.
为解决以下问题，研究了富含A+T的革兰氏阴性菌流感嗜血杆菌和富含G+C的革兰氏阳性菌结核分枝杆菌不同基因中三个密码子位点的密码子使用偏好和碱基组成偏差：（1）碱基组成高度偏斜的生物体中同义密码子的使用是否如先前报道的那样完全由突变偏差决定（夏普，P.M.，迪瓦恩，K.M.，1989年。盘基网柄菌中的密码子使用和基因表达水平：高表达基因确实“偏好”最优密码子。核酸研究。17，5029 - 5039），还是也受翻译选择的控制；（2）如在大肠杆菌中报道的那样（古铁雷斯，G.，马尔克斯，L.，马林，A.，1996年。大肠杆菌高表达基因中密码子第一位对鸟苷的偏好。与翻译效率的关系。核酸研究。24，2525 - 2527），高表达基因在密码子第一位对G的偏好在其他细菌中是否也成立；以及（3）三个密码子位点中碱基的使用是否具有物种特异性。这里呈现的结果表明，即使在具有高突变偏差的生物体中，翻译选择在决定同义密码子使用方面也起着重要作用，尽管最优密码子的集合是根据突变压力选择的。尽管结核分枝杆菌和流感嗜血杆菌的基因组富含A+T，但通过密码子适应指数（CAI）值估计，以G开头的密码子的频率与基因的表达水平呈正相关。因此，本研究对两种碱基组成偏斜相反的生物体的密码子偏好表明，高表达基因对以G开头的密码子的偏好可能是细菌的一个普遍特征，无论其总体G+C含量如何。流感嗜血杆菌和结核分枝杆菌基因的第一和第二密码子位点单个碱基频率的变化范围与大肠杆菌相似，这意味着尽管所有三个密码子位点的组成受选择 - 突变平衡的控制，但即使在碱基组成高度偏斜的生物体中，突变压力对前两个密码子位点碱基的选择影响很小。
