Selective advantages created by codon ambiguity allowed for the evolution of an alternative genetic code in Candida spp.

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 c ode is frozen and universal and prompt the questions 'why alternative genet ic codes evolved and, more importantly, how can an organism survive a genet ic code change?' To address these two questions, we have attempted to recon struct the early stages of Candida albicans CUG reassignment in the closely related yeast Saccharomyces cerevisiae, These studies suggest that this ge netic 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 in troduces an evolutionary edge to counteract the negative impact of ambiguit y. We have shown that CUG ambiguity induces the expression of a novel set o f stress proteins and triggers the general stress response, which, in turn, creates a competitive edge under stress conditions. In addition, CUG ambig uity in S. cerevisiae induces the expression of a number of novel phenotype s 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 sele ction and suggests a novel role for codon reassignment in the adaptation to new ecological niches.