Zhang S P, Zubay G, Goldman E
Fairchild Center for Biological Sciences, Columbia University, New York, NY 10027.
Gene. 1991 Aug 30;105(1):61-72. doi: 10.1016/0378-1119(91)90514-c.
Codon usage is compared between four classes of species, with an emphasis on characterization of low-usage codons. The classes of species analyzed include the bacterium Escherichia coli (ECO), the yeast Saccharomyces cerevisiae (YSC), the fruit fly Drosophila melanogaster (DRO), and several species of primates (PRI) (taken as a group; includes eleven species for which nucleotide sequence data have been reported to GenBank, however, greater than 90% of the sequences were from Homo sapiens). The number of protein-coding sequences analyzed were 968 for ECO, 484 for YSC, 244 for DRO, and 1518 for PRI. Three methods have been used to determine low-usage codons in these species. The first and most common way of assessing codon usage is by summing the number of time codons appear in reading frames of the genome in question. The second way is to examine the distribution of usage in different genes by scoring the number of protein reading frames in which a particular codon does not appear. The third way starts with a similar notion, but instead considers combinations of codons that are missing from the maximum number of genes. These three methods give very similar results. Each species has a unique combination of eight least-used codons, but all species contain the arginine codons, CGA and CGG. The agreement between YSC and PRI is particularly striking as they share six low-usage codons. All six carry the dinucleotide sequence, CG. The eight least-used codons in PRI include all codons that contain the CG dinucleotide sequence. Low-usage codons are clearly avoided in genes encoding abundant proteins for ECO, YSC DRO. In all species, proteins containing a high percentage of low-usage codons could be characterized as cases where an excess of the protein could be detrimental. Low codon usage is relatively insensitive to gross base composition. However, dinucleotide usage can sometimes influence codon usage. This is particularly notable in the case of CG dinucleotides in PRI.
对四类物种的密码子使用情况进行了比较，重点是低使用频率密码子的特征描述。所分析的物种类别包括细菌大肠杆菌（ECO）、酵母酿酒酵母（YSC）、果蝇黑腹果蝇（DRO）以及几种灵长类动物（PRI）（作为一个群体；包括已向GenBank报告核苷酸序列数据的11个物种，然而，超过90%的序列来自智人）。分析的蛋白质编码序列数量分别为：大肠杆菌968个、酿酒酵母484个、黑腹果蝇244个、灵长类动物1518个。已使用三种方法来确定这些物种中的低使用频率密码子。评估密码子使用情况的第一种也是最常见的方法是将密码子在所讨论基因组的阅读框中出现的次数相加。第二种方法是通过对特定密码子未出现的蛋白质阅读框数量进行评分，来检查不同基因中的使用分布情况。第三种方法从类似的概念出发，但考虑的是在最多数量的基因中缺失的密码子组合。这三种方法得出的结果非常相似。每个物种都有一个由八个使用频率最低的密码子组成的独特组合，但所有物种都包含精氨酸密码子CGA和CGG。酿酒酵母和灵长类动物之间的一致性尤为显著，因为它们共享六个低使用频率密码子。所有六个密码子都携带二核苷酸序列CG。灵长类动物中八个使用频率最低的密码子包括所有包含CG二核苷酸序列的密码子。对于大肠杆菌、酿酒酵母和黑腹果蝇，在编码丰富蛋白质的基因中显然避免使用低使用频率密码子。在所有物种中，含有高比例低使用频率密码子的蛋白质可被视为蛋白质过量可能有害的情况。低密码子使用对总体碱基组成相对不敏感。然而，二核苷酸使用有时会影响密码子使用。这在灵长类动物中CG二核苷酸的情况下尤为明显。
