Scientists have engineered the first living microbe that can carry and pass down an expanded genetic code to future generations — one that has six base pairs instead of the usual four. It's a breakthrough that will not only allow us to build powerful new forms of life, it's also changing what we know about evolution.
It's the result of nearly 15 years of work — a reconstituted version of the E. coli bacteria that boasts two artificial base blocks of DNA. The new semi-synthetic organism, with its expanded genetic alphabet, gives rise to further possibilities, including novel cells that can produce drugs and other useful molecules, or more conceptually, cells and organisms without any of the four DNA bases currently used by all creatures on Earth.
But there's more to this breakthrough than just this. It shows that DNA is far more dynamic and malleable that we thought, and that if we were to rewind and restart Earth's evolutionary clock, an entirely different molecule could have emerged.
"This has very important implications for our understanding of life," noted lead researcher Floyd Romesberg in a Guardian article. "For so long people have thought that DNA was the way it was because it had to be, that it was somehow the perfect molecule."
Indeed, all life on Earth has been written with the exact same DNA code of four letters — and it's been that way since day one.
Each strand of the DNA's double helix has four "building block" bases attached to them, adenine (A), thymine (T), cytosine (C) and guanine (G). Our DNA can be written using this simple four-letter alphabet. The bases bind the two DNA strands together, where A bonds with T (and vice versa), while C and G do the same. In humans, these four letters make up the entire three billion base pairs of our genetic code. These base pairs make our genes, which are used by cells as templates for making proteins.
All the diversity of life on Earth is encoded by these two pairs of DNA bases, A-T and C-G. But what Romesberg and his team at the Scripps Research Institute in California has done is create an organism that stably contains the regular two, plus a third, synthetic pair of bases. According to the researchers, this shows that other solutions to storing genetic information may be possible. If so, it could result in an expanded-DNA biology that's likely to introduce many new possibilities, from new medicines to all kinds of nanotechnology.
The extra fifth and sixth letters have been dubbed X and Y, thus forming a third base pair, X-Y. To make the synthetic DNA work, a loop of genetic material was inserted into an E. coli bacterium that carried normal DNA and the third X-Y pair (also referred to by their longer chemical names, d5SICS and dNaM).
The researchers found that, when the bacteria divided, they successfully passed on the natural DNA. And incredibly, they also copied and passed down the synthetic code on to the next generation. The subsequent generation did likewise. This research, which now appears in Nature, shows for the very first time that an organism can stably host a third base pair while still maintaining its ability to harbor natural ones.
For now, the third base pair does nothing in the cell. The next step will be to modify the organism such that it can actually do something useful with its synthetic components.
There's no shortage of ideas. By expanding the genetic alphabet, and by allowing more data to be stored in DNA, scientists could develop new drugs, diagnostic tools, vaccines, and nanomaterials. Other possibilities include biological circuits and cells that don't exist in nature.
Lastly, it's important to note that, for safety reasons, the unnatural DNA has a built-in safety mechanism; the modified E. coli can only survive if it's fed certain chemicals required to replicate the DNA.
Read the entire study at Nature: "A semi-synthetic organism with an expanded genetic alphabet." Supplementary information via Synthorx, Nature News, Telegraph, and Guardian.