Genetic code ambiguity: an unexpected source of proteome innovation and phenotypic diversity

Translation of the genome into the proteome is a highly accurate biological process. However, the molecular mechanisms involved in protein synthesis are not error free and downstream protein quality control systems are needed to counteract the negative effects of translational errors (mistranslation) on proteome and cell homeostasis. This plus human and mice diseases caused by translational error generalized the idea that codon ambiguity is detrimental to life. Here we depart from this classical view of deleterious translational error and highlight how codon ambiguity can play important roles in the evolution of novel proteins. We also explain how tRNA mischarging can be relevant for the synthesis of functional proteomes, how codon ambiguity generates phenotypic and genetic diversity and how advantageous phenotypes can be selected, fixed, and inherited. A brief introduction to the molecular nature of translational error is provided; however, detailed information on the mechanistic aspects of mistranslation or comprehensive literature reviews of this topic should be obtained elsewhere.