An open challenge in evolutionary cell biology is to identify the mechanisms by which the translation machinery adapts. In this work, we focus on the balance between translational demand (codon usage) and translational supply (tRNA pool), which is crucial for the efficiency of protein translation. Since many parts of the translation machinery do not demonstrate evolutionary flexibility, the maintenance mechanisms of the translational balance are not fully known.
Recently, we manipulated the supply arm of the translation balance by deleting a tRNA gene that appears in the genome of saccharomyces cerevisiae in a single copy. Using a combination of lab-evolution experiments and comparative genomics, we revealed a new adaptation mechanism of the tRNA pool that we termed “anticodon switching”. This novel mechanism is based on mutations in the anticodons of tRNA genes that essentially can convert one tRNA type into another. Accordingly, a new theory that emerges from our study suggests that tRNA genes are connected through a conceptual evolutionary network and provide a source of evolutionary plasticity to the translation machinery.
To deepen our understanding on the anticodon switching mechanism and to reveal other adaptation mechanisms, we turned to manipulate the demand arm of the translation equilibrium. We utilized genome engineering technologies and introduced 60 synonymous mutations to the genome of Escherichia coli that convert common codons to a rare codon. Currently, lab-evolution experiments, together with other phenotypic assays are applied to reveal new insight regarding the translation apparatus and its evolution.
