At the time of its discovery four decades ago, the genetic code was viewed as the result of a “frozen accident.” Our current knowledge of the translation process and of the detailed structure of its components highlights the roles of RNA structure (in mRNA and tRNA), RNA modification (in tRNA), and aminoacyl-tRNA synthetase diversity in the evolution of the genetic code. The diverse assortment of codon reassignments present in subcellular organelles and organisms of distinct lineages has 'thawed' the concept of a universal immutable code; it may not be accidental that out of more than 140 amino acids found in natural proteins, only two (selenocysteine and pyrrolysine) are known to have been added to the standard 20-member amino acid alphabet. The existence of phosphoseryl-tRNA (in the form of tRNACys and tRNASec) may presage the discovery of other cotranslationally inserted modified amino acids.
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We thank P. Agris for critical comments on the paper. S.P. holds a fellowship of the Yale University School of Medicine MD/PhD Program. Work in the authors' laboratory was supported by grants from the US National Institute of General Medical Sciences (GM22854), the US Department of Energy (DE-FG02-98ER20311) and the US National Science Foundation (DBI-0535566).
The authors declare no competing financial interests.
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Ambrogelly, A., Palioura, S. & Söll, D. Natural expansion of the genetic code. Nat Chem Biol 3, 29–35 (2007). https://doi.org/10.1038/nchembio847
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