Britten R J
Division of Biology, California Institute of Technology.
Mol Biol Evol. 1993 Jan;10(1):205-20. doi: 10.1093/oxfordjournals.molbev.a039996.
In the evolution of highly conserved genes, a few "synonymous" substitutions at third bases that would not alter the protein sequence are forbidden or very rare, presumably as a result of functional requirements of the gene or the messenger RNA. Another 10% or 20% of codons are significantly less variable by synonymous substitution than are the majority of codons. The changes that occur at the majority of third bases are subject to codon usage restrictions. These usage restrictions control sequence similarities between very distant genes. For example, 70% of third bases are identical in calmodulin genes of man and trypanosome. Third-base similarities of distant genes for conserved proteins are mathematically predicted, on the basis of the G+C composition of third bases. These observations indicate the need for reexamination of methods used to calculate synonymous substitutions.
在高度保守基因的进化过程中，第三碱基处一些不会改变蛋白质序列的“同义”替换是被禁止的或非常罕见的，推测这是基因或信使核糖核酸功能需求的结果。另外10%或20%的密码子通过同义替换的可变程度明显低于大多数密码子。大多数第三碱基处发生的变化受到密码子使用限制。这些使用限制控制着非常远缘基因之间的序列相似性。例如，人类和锥虫钙调蛋白基因中70%的第三碱基是相同的。基于第三碱基的G+C组成，从数学上预测了保守蛋白质远缘基因的第三碱基相似性。这些观察结果表明需要重新审视用于计算同义替换的方法。
