Towards a code that governs translation fidelity

The translation machinery and the genes it decodes co-evolved to achieve production throughput and accuracy. Nonetheless, translation errors are frequent, and they affect physiology and protein evolution. Mapping translation errors in proteomes and understanding their causes is hindered by lack of a proteome-wide experimental methodology. We developed a computational methodology to systematic detect and quantification all errors made during transaltion in entire proteomes. Most substitutions result from codon-anticodon mispairing, others appear to be made during tRNA charging. Errors occur at sites that evolve rapidly and that minimally affect energetic stability, indicating selection for high translation fidelity. Ribosome density data show that errors occur at sites where ribosome velocity is higher, demonstrating a trade-off between speed and accuracy. These results reveal a mechanistic and evolutionary basis for translation fidelity.

In collaboration with Orna Dahan, Tamar Geiger and Ariel Lindner