Hou Zhuo-Cheng, Yang Ning
College of Animal Science and Technology, China Agricultural University, Beijing 100094, China.
Yi Chuan Xue Bao. 2002;29(8):747-52.
Streptococcus pneumoniae is a Gram-positive bacteria causing community acquired pneumonia, bacteremia, meningitis and otitis media. As a human pathogen, S. pneumoniae is the most common bacterial cause of acute respiratory infection and otitis media and is estimated to result in over 3 million deaths in children every year worldwide. S. pneumoniae has played a pivotal role in the fields of genetics and microbiology. The complete genome of S. pneumoniae was sequenced and published recently. In order to have a further insight into the synonymous codon usage evolution and to study S. pneumoniae gene codon usage pattern in highly and lowly expressed genes, factors shaping synonymous codon usage pattern of S. pneumoniae were analyzed in this paper. Genes larger than of equal to 300bp of the complete genome of S. pneumoniae (1709 genes in total) were analyzed. The gene expression level (CAI, codon adaption index), RSCU (relative synonymous codon usage), Nc (effective codon numbers), A3s, T3s, G3s, C3s (the frequencies of the adenine, thymine, guanine and cytosine at the synonymous third position of codons, respectively), GC (frequency of guanine + cytosine in gene sequence), GC3s (frequency of guanine + cytosine at the synonymous third position of codons) values and multivariate statistics were calculated. The results show that there is a significant increment of cytosine (C) usage at the synonymous positions in highly expressed genes than lowly expressed genes, while lowly expressed genes tend to use guanine (G) at synonymous sites. Gene expression has a significant correlation with the first axis of correspondence analysis (COA; R = 0.86) and significant effects on codon usage by comparing the codon usage patterns of highly expressed genes and lowly expressed genes. The G + C content of genes has a moderately correlation with gene expression (R = 0.44) and the first axis of the COA (R = 0.51), and therefore shapes gene expression and codon usage in S. pneumoniae. The dataset is divided into 6 groups by gene length. Then, gene expression level, GC3s and Nc values are compared among 6 different gene length groups (> = 300 bp, 2000-2999 bp, 1500-1999 bp, 1000-1499 bp, 500-999 bp, < 500 bp). CAI, GC3s and Nc values show some differences among different gene length groups. Protein hydrophobicities do not show significant influence on codon usage pattern. In summary, the natural selection on gene expression level and the base composition of genes are the major factors affecting codon usage of S. pneumoniae. Gene length shapes codon usage of S. pneumoniae in a minor way.
肺炎链球菌是一种革兰氏阳性细菌，可引起社区获得性肺炎、菌血症、脑膜炎和中耳炎。作为一种人类病原体，肺炎链球菌是急性呼吸道感染和中耳炎最常见的细菌病因，据估计，全球每年有超过300万儿童死于肺炎链球菌感染。肺炎链球菌在遗传学和微生物学领域发挥了关键作用。肺炎链球菌的完整基因组最近已被测序并公布。为了进一步深入了解同义密码子使用的进化情况，并研究肺炎链球菌在高表达和低表达基因中的基因密码子使用模式，本文分析了影响肺炎链球菌同义密码子使用模式的因素。分析了肺炎链球菌完整基因组中长度大于或等于300bp的基因（总共1709个基因）。计算了基因表达水平（密码子适应指数，CAI）、相对同义密码子使用（RSCU）、有效密码子数（Nc）、A3s、T3s、G3s、C3s（分别为密码子同义第三位的腺嘌呤、胸腺嘧啶、鸟嘌呤和胞嘧啶的频率）、GC（基因序列中鸟嘌呤+胞嘧啶的频率）、GC3s（密码子同义第三位的鸟嘌呤+胞嘧啶的频率）值以及多元统计量。结果表明，高表达基因在同义位置上胞嘧啶（C）的使用量比低表达基因有显著增加，而低表达基因在同义位点倾向于使用鸟嘌呤（G）。通过比较高表达基因和低表达基因的密码子使用模式，基因表达与对应分析的第一轴（COA；R = 0.86）有显著相关性，并且对密码子使用有显著影响。基因的G + C含量与基因表达（R = 0.44）和COA的第一轴（R = 0.51）有中度相关性，因此影响肺炎链球菌的基因表达和密码子使用。数据集按基因长度分为6组。然后，比较了6个不同基因长度组（>= 300 bp、2000 - 2999 bp、1500 - 1999 bp、1000 - 1499 bp、500 - 999 bp、< 500 bp）中的基因表达水平、GC3s和Nc值。CAI、GC3s和Nc值在不同基因长度组之间存在一些差异。蛋白质疏水性对密码子使用模式没有显著影响。总之，基因表达水平的自然选择和基因的碱基组成是影响肺炎链球菌密码子使用的主要因素。基因长度对肺炎链球菌密码子使用的影响较小。
