Santos M A, Cheesman C, Costa V, Moradas-Ferreira P, Tuite M F
Research School of Biosciences, University of Kent, Canterbury, UK.
Mol Microbiol. 1999 Feb;31(3):937-47. doi: 10.1046/j.1365-2958.1999.01233.x.
Several species of the genus Candida decode the standard leucine CUG codon as serine. This and other deviations from the standard genetic code in both nuclear and mitochondrial genomes invalidate the notion that the genetic code is frozen and universal and prompt the questions 'why alternative genetic codes evolved and, more importantly, how can an organism survive a genetic code change?' To address these two questions, we have attempted to reconstruct the early stages of Candida albicans CUG reassignment in the closely related yeast Saccharomyces cerevisiae. These studies suggest that this genetic code change was driven by selection using a molecular mechanism that requires CUG ambiguity. Such codon ambiguity induced a significant decrease in fitness, indicating that CUG reassignment can only be selected if it introduces an evolutionary edge to counteract the negative impact of ambiguity. We have shown that CUG ambiguity induces the expression of a novel set of stress proteins and triggers the general stress response, which, in turn, creates a competitive edge under stress conditions. In addition, CUG ambiguity in S. cerevisiae induces the expression of a number of novel phenotypes that mimic the natural resistance to stress characteristic of C. albicans. The identification of an evolutionary advantage created by CUG ambiguity is the first experimental evidence for a genetic code change driven by selection and suggests a novel role for codon reassignment in the adaptation to new ecological niches.
念珠菌属的几个物种将标准的亮氨酸CUG密码子解码为丝氨酸。这种情况以及核基因组和线粒体基因组中其他与标准遗传密码的偏差，使遗传密码是固定不变且通用的这一观念站不住脚，并引发了“为什么会进化出替代遗传密码，更重要的是，生物体如何在遗传密码改变的情况下存活下来？”这两个问题。为了解决这两个问题，我们试图在密切相关的酿酒酵母中重建白色念珠菌CUG重新分配的早期阶段。这些研究表明，这种遗传密码的改变是由一种需要CUG模糊性的分子机制驱动的选择所导致的。这种密码子模糊性导致了适应性的显著下降，这表明只有当CUG重新分配引入一种进化优势以抵消模糊性带来的负面影响时，它才能被选择。我们已经表明，CUG模糊性会诱导一组新的应激蛋白的表达并触发一般应激反应，进而在应激条件下创造出竞争优势。此外，酿酒酵母中的CUG模糊性会诱导许多新表型的表达，这些表型模仿了白色念珠菌对压力的天然抗性特征。由CUG模糊性产生的进化优势的鉴定是由选择驱动的遗传密码改变的首个实验证据，并表明密码子重新分配在适应新生态位方面具有新的作用。
