Synthetic microbe lives with less than 500 genes
When it comes to genome size, a rare Japanese flower, called Paris japonica, is the current heavyweight champ, with 50 times more DNA than humans. At the other end of the scale, there’s now a new lightweight record-holder growing in petri dishes in California. This week in
Science, researchers led by genome sequencing pioneer Craig Venter report engineering a bacterium to have the smallest genome—and the fewest genes—of any freely living organism, smaller than the flower’s by a factor of 282,000. Known as Syn 3.0, the new organism has a genome whittled down to the bare essentials needed to survive and reproduce, just 473 genes. “It’s a tour de force,” says George Church, a synthetic biologist at Harvard University.
The microbe’s streamlined genetic structure excites evolutionary biologists and biotechnologists, who anticipate adding genes back to it one by one to study their effects. “It’s an important step to creating a living cell where the genome is fully
defined,” says synthetic biologist Chris Voigt of the Massachusetts Institute of Technology in Cambridge. But Voigt and others note that this complete definition remains a ways off, because the function of 149 of Syn 3.0’s genes—roughly one-third—
remains unknown. Investigators’ first task is to probe the roles of those genes, which promise new insights into the basic biology of life.
As Syn 3.0’s name suggests, it’s not the first synthetic life made by Venter, who heads the J. Craig Venter Institute (JCVI) and is a founder of Synthetic Genomics, a biotech company, both in San Diego, California. In 2010, Venter’s team reported that they had synthesized the sole chromosome of Mycoplasma mycoides—a bacterium with a relatively small genome—and transplanted it into a separate mycoplasma called M. capricolum, from which they had previously extracted the DNA. After several false starts, they showed that the synthetic microbe booted up and synthesized proteins normally made by M. mycoides rather than M. capricolum (Science, 21 May 2010,
p. 958). Still, other than adding a bit of watermark DNA, the researchers left the genetic material in their initial synthetic organism, Syn 1.0, unchanged from
the parent.
In their current work, Venter, along with project leader Clyde Hutchison at JCVI, set out to determine the minimal set of genes needed for life by stripping nonessential genes from Syn 1.0. They initially formed two teams, each with the same task: using all available genomic knowledge to design a bacterial chromosome with the hypothetical minimum genome. Both proposals were then synthesized and transplanted into
M. capricolum to see whether either would produce a viable organism.
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