Recipe for life
It takes more than rational design to reboot life.
IT APPEARED THE BASIC RECIPE FOR LIFE REQUIRED FAR FEWER ESSENTIAL GENES.
What’s the recipe for life? Eye of newt, toe of frog…? Craig Venter has a more modern version: his recipe calls for just 473 genes.
Venter’s team at the James Craig Venter Institute in Maryland, US, announced their discovery in March in the journal Science.
To come up with the simplest possible recipe, the team began with a bacterium known as Mycoplasma mycoides. Its 901 genes are all it needs to thrive within the lungs of cattle; most bacteria need closer to 5,000. Diminutive as it is, many of M. mycoides’ genes are non-essential. Venter’s team showed this by disrupting each gene by inserting bits of foreign code. It appeared the basic recipe for life required far fewer essential genes.
But to prove that, Venter’s team heeded the words of physicist Richard Feynman: “What I cannot create, I do not understand.” Their goal was to build a full-length genetic code in the lab, then pare it down to find the minimum set.
In 2010, the team achieved the first part. They created “Syn 1.0”, the first artificial life form. Made by stringing the right sequence of four DNA letters together, the synthetic genome was “rebooted” by incubating it in another species of Mycoplasma. Though Syn 1.0 starts off life with a borrowed shell, after a few divisions, the organism is entirely constructed according to the instructions of the synthetic genome, the team showed.
The next goal was to pare that genome down to its essential elements.
The team began by designing a genome containing the genes predicted to be essential. But this rationally designed genome would not reboot. “Our current knowledge of biology is not sufficient to sit down and design a living organism and build it,” Venter conceded.
Undaunted, the team resorted to trial and error, mixing and matching smaller strings of DNA, stitching them up, and trying to reboot them. Six years and hundreds of genomes later, they finally found a 473-gene combination that rebooted life. “Syn 3.0” grew with a respectable three-hour doubling time.
Besides building the smallest functional genome yet known, the project has a practical side. It enables the design of bespoke organisms for industrial tasks such as the production of biofuels or drugs.
“Syn 3.0 is a chassis cell; now we can bolt modules on it,” says synthetic biologist Claudia Vickers at the University of Queensland.
So is the mystery of life solved? Not really. Venter’s team cannot account for the function of 149 of Syn 3.0’s 473 genes. “Life is only marginally less mysterious,” says molecular biologist John Mattick, who heads Sydney’s Garvan Institute.
It seems there is still a bit of “eye of newt” to Venter’s recipe after all.