School of Biological Science and Technology, Shenyang Agricultural University, Shenyang, PR China.
BMC Bioinformatics. 2010 Jan 28;11:61. doi: 10.1186/1471-2105-11-61.
Codon bias is believed to play an important role in the control of gene expression. In Escherichia coli, some rare codons, which can limit the expression level of exogenous protein, have been defined by gene engineering operations. Previous studies have confirmed the existence of codon pair's preference in many genomes, but the underlying cause of this bias has not been well established. Here we focus on the patterns of rarely-used synonymous codons. A novel method was introduced to identify the rare codons merely by codon pair bias in Escherichia coli.
In Escherichia coli, we defined the "rare codon pairs" by calculating the frequency of occurrence of all codon pairs in coding sequences. Rare codons which are disliked in genes could make great contributions to forming rare codon pairs. Meanwhile our investigation showed that many of these rare codon pairs contain termination codons and the recognized sites of restriction enzymes. Furthermore, a new index (F(rare)) was developed. Through comparison with the classical indices we found a significant negative correlation between F(rare) and the indices which depend on reference datasets.
Our approach suggests that we can identify rare codons by studying the context in which a codon lies. Also, the frequency of rare codons (F(rare)) could be a useful index of codon bias regardless of the lack of expression abundance information.
密码子偏好被认为在基因表达调控中起着重要作用。在大肠杆菌中，通过基因工程操作已经定义了一些可能限制外源蛋白表达水平的稀有密码子。先前的研究已经证实了许多基因组中存在密码子对偏好，但这种偏好的潜在原因尚未得到很好的确定。在这里，我们关注的是很少使用的同义密码子的模式。我们介绍了一种新的方法，仅通过大肠杆菌中密码子对偏好来识别稀有密码子。
在大肠杆菌中，我们通过计算编码序列中所有密码子对的出现频率来定义“稀有密码子对”。在基因中不受欢迎的稀有密码子可以为形成稀有密码子对做出巨大贡献。同时，我们的研究表明，这些稀有密码子对中有许多包含终止密码子和限制酶的识别位点。此外，我们还开发了一个新的指数（F（rare））。通过与经典指数的比较，我们发现 F（rare）与依赖参考数据集的指数之间存在显著的负相关。
我们的方法表明，我们可以通过研究密码子所处的上下文来识别稀有密码子。此外，无论缺乏表达丰度信息如何，稀有密码子的频率（F（rare））都可以作为密码子偏好的有用指标。
