A genetic code with 6 letters: A, C, G, T, X, and Y?

We're all familiar with the central dogma of biology - or at least we should be. I remember first learning it back in Dr. Campisi's Molecular and Cell Biology class. DNA is transcribed into RNA, which is then translated into proteins. This central dogma has formed the basis of our understanding of genetics and all forms of life on earth. DNA has 2 base pairs: adenosine (A) to thymine (T), and cytosine (C) to guanine (G). This is true of all life on earth. Or it was, at least, until recently.

Back in 2014, researchers successfully created the first synthetic nucleotide base pair. The artificial base pair does not engage in hydrogen bonding like the A-T and C-G base pairs do; rather, X and Y bond through hydrophobic interactions, which may limit the number of synthetic bases that can be integrated without disrupting the helical structure of DNA. This opened up new possibilities for the world of synthetic biology, and has sparked research into

Last week, a paper was published in Nature magazine. The researchers were able to demonstrate that the XY base pair can replicate in living bacterial cells, create atypical proteins, and partake in information storage (Zhang et al., 2017). First the researchers placed the X-Y pair into the green fluorescent protein (GFP) gene, which changed a codon from TAC to AXC. RNA created the anti-codon, GYT, and that was translated into the GFP protein containing a novel artificial amino acid. The gene was expressed in semi-synthetic bacteria which produced GFP proteins with the synthetic amino acid.

This is a monumental development. The central dogma of biology has been retained even with a synthetic base pair. The potential for synthetic biology is now suddenly much more feasible, with the promise of new medications and synthetic organisms. However, there is much work to do, and there is certainly much criticism over the stability and efficiency of the new alphabet: after all, there are now two more letters to think about, but millions more combinations of DNA that could potentially alter life on the planet.

Zhang, Y., Ptacin, J. L., Fischer, E. C., Aerni, H. R., Caffaro, C. E.,  San Jose, K., . . . & Romesberg, F. E. (2017). A semi-synthetic organism that stores and retrieves increased genetic information. Nature, 551, 644-647. doi:10.1038/nature24659

Link to full article without paywall: https://sci-hub.bz/https://www.nature.com/articles/nature24659