Simplification of the genetic code: Restricted diversity of genetically encoded amino acids

Akio Kawahara-Kobayashi, Akiko Masuda, Yuhei Araiso, Yoko Sakai, Atsushi Kohda, Masahiko Uchiyama, Shun Asami, Takayoshi Matsuda, Ryuichiro Ishitani, Naoshi Dohmae, Shigeyuki Yokoyama, Takanori Kigawa, Osamu Nureki, Daisuke Kiga*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)


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. Here, we constructed artificial genetic codes involving a reduced alphabet. In one of the codes, a tRNAAla 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, green fluorescent protein 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.

Original languageEnglish
Pages (from-to)10576-10584
Number of pages9
JournalNucleic acids research
Issue number20
Publication statusPublished - 2012 Nov
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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