The fact that the canonical genetic code is nearly universal is thought to allow natural organisms to share beneficial traits via horizontal gene transfer. However, given that genetically modified organisms also share the same genetic code, they are susceptible to viruses and capable of releasing recombinant genetic material, such as resistance genes, into the environment.
By redefining the genetic code, Lajoie et al hope to produce genomically recoded organisms that are safe and useful. They reassigned the translation function of the UAG stop codon in Escherichia coli without impairing fitness. More specifically, they replaced all known UAG stop codons with synonymous UAA stop codons thereby eliminating natural UAG translation function. UAG was then reassigned as a dedicated codon to genetically encode nonstandard amino acids while avoiding deleterious incorporation at native UAG positions. The engineered E. coli incorporated nonstandard amino acids into its proteins and showed enhanced resistance to bacteriophage T7.
In a second paper, Lajoie et al. demonstrated the recoding of 13 codons in 42 highly expressed essential genes in E. coli. Reassigning sense codons is more challenging because they are more prevalent, and their usage regulates gene expression in ways that are difficult to predict. The results by Lajoie et al. suggest that the genome-wide removal of 13 codons was feasible; however, synonymous codons occasionally were nonequivalent in unpredictable ways.
Genomically recoded organisms expand biological functions. Lajoie MJ, Rovner AJ, Goodman DB, Aerni HR, Haimovich AD, Kuznetsov G, Mercer JA, Wang HH, Carr PA, Mosberg JA, Rohland N, Schultz PG, Jacobson JM, Rinehart J, Church GM, Isaacs FJ. Science. 2013 Oct 18;342(6156):357-60. PMID: 24136966
Probing the limits of genetic recoding in essential genes. Lajoie MJ, Kosuri S, Mosberg JA, Gregg CJ, Zhang D, Church GM. Science. 2013 Oct 18;342(6156):361-3. doi: 10.1126/science.1241460. PMID: 24136967
Posted by Yannis Trakadis, MD