Simplification of the Genetic Code: Restricted Diversity of Genetically Encoded Amino Acids

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Daisuke Kiga

Tokyo Institute of Technology, Japan

At earlier stages in the evolution of the universal genetic code, fewer than 20 amino acids were considered to be used. Although this notion is supported by a wide range of data, the actual existence and function of the genetic codes with a limited set of canonical amino acids have not been addressed experimentally, in contrast to the successful development of the expanded codes. Recently, we constructed artificial genetic codes involving a reduced alphabet [1]. In one of the codes, a tRNA(Ala) variant with the Trp anticodon reassigns alanine to an unassigned UGG codon in the Escherichia coli S30 cell-free translation system lacking tryptophan. We confirmed that the efficiency and accuracy of protein synthesis by this Trp-lacking code were comparable to those by the universal genetic code, by an amino acid composition analysis, GFP fluorescence measurements and the crystal structure determination. We also showed that another code, in which UGU/UGC codons are assigned to Ser, synthesizes an active enzyme. This method will provide not only new insights into primordial genetic codes, but also an essential protein engineering tool for the assessment of the early stages of protein evolution and for the improvement of pharmaceuticals. In this presentation, we will show the generality of our method for the simplification, by constructing other types of further simplified codes including a 16-amino-acid code.