Genomic information is generally encoded based on a two-base-pair genetic alphabet (A–T and G–C). In vitro, the alphabet has been expanded to include several unnatural base pairs (UBPs).
One such UBP is the pair formed between d5SICS and dNaM (d5SICS–dNaM) nucleotides bearing hydrophobic nucleobases. d5SICS–dNaM is efficiently PCR-amplified and transcribed in vitro, and its unique mechanism of replication has been previously characterized.
Malyshev et al. (2014) show that an exogenously expressed algal nucleotide triphosphate transporter efficiently imports the triphosphates of both d5SICS and dNaM (d5SICSTP and dNaMTP) into E. coli, and that the endogenous replication machinery uses them to accurately replicate a plasmid containing d5SICS–dNaM. No notable growth burden was reported and the findings suggest that UBP is not efficiently excised by DNA repair pathways.
The authors conclude that the resulting bacterium is the first organism to propagate stably an expanded genetic alphabet.
A semi-synthetic organism with an expanded genetic alphabet. Malyshev DA, Dhami K, Lavergne T, Chen T, Dai N, Foster JM, Corrêa IR Jr, Romesberg FE. Nature. 2014 May 15;509(7500):385-8. PMID: 24805238
Posted by Yannis Trakadis, MD