New letters for life's alphabet

• Published in: Nature (London) Vol. 509; no. 7500; pp. 291 - 292
• Main Authors: Thyer, Ross, Ellefson, Jared
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15-05-2014; Nature Publishing Group
• Subjects: 631/337; 631/92; 631/92/552; Algae; Amino acids; Deoxyribonucleic acid; DNA; E coli; Enzymes; Gene expression; Human genetics; Humanities and Social Sciences; multidisciplinary; news-and-views; Nucleic acids; Plasmids; Properties; Proteins; Science; United Kingdom
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature13335

The five bases found in nucleic acids define the 'alphabet' used to encode life on Earth. The construction of an organism that stably propagates an unnatural DNA base pair redefines this fundamental feature of life.
See Letter
p.385
A bacterium using an expanded genetic alphabet
The genetic code is simple: four bases that form two pairs (A–T and G–C) are used in all of life. Expansion of this code to incorporate unnatural nucleotides and base pairing has been a goal of synthetic biology, as it would open up ways to tailor organisms for directed purposes. Although this has been achieved in proof-of-principle experiments
in vitro
, stable propagation of an expanded code had not been demonstrated
in vivo
until now. Floyd Romesberg and colleagues present evidence that two hydrophobic nucleotides, d5SICSTP and dNaMTP, can be added to the medium in which
Escherichia coli
expressing an exogenous algal nucleotide triphosphate transporter is growing, and that these nucleotides will be incorporated in the genome and are not recognized as lesions by the repair pathway. Consequently, the unnatural-base-pair-containing DNA is replicated, without cell growth being significantly affected.