Scientists engineer organism with expanded genetic alphabet

Bacteria with two extra synthetic DNA bases in their genome have been created in the lab for the first time.

Instead of just the four bases, or 'letters', that make up the DNA of all known organisms - adenine (A), thymine (T), cytosine (C), and guanine (G) - the modified E.coli bacteria have six.

'Life on Earth in all its diversity is encoded by only two pairs of DNA bases, A-T and C-G, and what we've made is an organism that stably contains those two plus a third, unnatural pair of bases', said Dr Floyd Romesberg, who led the research.

'This shows that other solutions to storing information are possible and, of course, takes us closer to an expanded-DNA biology that will have many exciting applications - from new medicines to new kinds of nanotechnology'.

Scientists at the Scripps Research Institute, USA, created two new bases called d5SICS and dNaM, dubbed X and Y, which were designed to pair with one another. When small rings of DNA called plasmids that contained these synthetic bases were added to E.coli, along with a transporter protein, the bacteria began to incorporate the new bases into its own DNA.

The bacteria grew and reproduced as normal, and were also able to pass their expanded genetic makeup onto subsequent generations.

DNA encodes amino acids, which make up proteins, with each set of three bases coding for one amino acid. Because there are now more bases, the scientists hope that this will mean that previously undiscovered amino acids, and therefore proteins, could be made. The researchers have suggested that it may be possible to produce around 200 amino acids from six bases: a tenfold increase on the twenty amino acids seen in nature.

'In principle, we could encode new proteins made from new, unnatural amino acids - which would give us greater power than ever to tailor protein therapeutics and diagnostics and laboratory reagents to have desired functions', Dr Romesberg said. 'Other applications, such as nanomaterials, are also possible'.

So far, the base-pairs have only been inserted into a non-coding part of the genome so the researchers have not been able to produce new amino acids.

Critics have brought up safety concerns surrounding such genetically modified organisms, but the researchers believe that their method is inherently safe.

'Our new bases can only get into the cell if we turn on the "base transporter" protein. Without this transporter or when the new bases are not provided, the cell will revert back to A, T, G, C and the d5SICS and the dNaM will disappear from the genome', said lead author Dr Denis Malyshev.

Commenting on the research in a Nature article, Dr Ross Thyer and Jared Ellefson from the University of Texas wrote: 'Attempts to expand the genetic alphabet bravely question the idea of the universal nature of DNA, and potentially draw criticism about the wisdom of tinkering with it'.