New letters in the DNA alphabet

A new pair of artificial DNA letters have been engineered into bacteria by US scientists.

The discovery of the structure of DNA in the 1950s by biochemical pioneers James Watson and Francis Crick revealed that life's recipe book is written using an alphabet of 4 letters, A, C, T and G.

Now a team in the US have created two new letters, catchily called d5SICS and dNAM, and persuaded E. coli bacteria to incorporate and use them.

The synthetic nucleotides were written into a small circle of DNA called a plasmid, alongside a gene coding for resistance to an antibiotic. So long as the bugs kept the synthetic DNA letters in the plasmid, the antibiotic resistance gene would remain active, enabling the bacteria to grow despite the antibiotic being present.

The artificial DNA letters were added by the scientists to the bacterial culture medium. To enable the bugs to pick them up, Scripps Institute scientist Floyd Romesburg and his colleagues also added a transporter gene, called NTT, borrowed from algae, to move them inside the cells.

Thus equipped, and so long as the scientists maintained the supply of the new nucleotides in the culture media, the bacteria multiplied, producing and sharing copies of the plasmid containing the new genetic letters.

Introducing new genetic letters like this opens up a whole new vista of gene manipulation. New genetic codes can be written so that new synthetic chemicals can be used by cells and assembled into complex compounds and specialised switches can be engineered into DNA to control gene activity.

But, as commentators Ross Thyer and Jared Ellefson ask in a News and Views article in Nature, where the research is published, given the ability to expand the genetic alphabet in this way, one must ask why life settled in the first place on just the four genetic letters seen naturally?