Genome from a Bottle Turns One Bacterium into Another: Wholesale DNA Swap Marks Synthetic Biology Milestone

Article excerpt

Using a made-from-scratch genome, scientists have breathed a new kind of life into a bacterium. The feat, published online May 20 in Science, holds promise for designing new organisms that might do things like produce vaccines, synthesize biofuels, purify water or eat spilled oil.

Researchers from the J. Craig Venter Institute carefully stitched together the entire genome of the bacterium Mycoplasma mycoides and put it into a different kind of bacterium, Mycoplasma capricolum. This unprecedented wholesale genome swap caused the M. capricolum cell to switch species. The newly converted cell was nearly identical to the natural M. mycoides.

"This was a proof-of-concept experiment showing that we could take the sequence out of a computer, build it and boot it up to make a synthetic cell," says studyleader Daniel Gibson of the Venter Institute's campus in Rockville, Md.

This ability to transplant complete genomes from one species to another is "a marvelous piece of work," says bioengineer James Collins, a Howard Hughes Medical Institute investigator at Boston University who was not involved in the study. "This represents an important advance for synthetic biology."

For decades biologists have been sculpting genomes by adding and subtracting bits of DNA, with the goal of gaining control over existing organisms--and even creating new ones.

Scientists at the Venter Institute already knew the DNA sequence of the M. mycoides genome. But now they've been able to take the string of A's, T's, G's and C's stored in a computer, build the whole genetic instruction book in test tubes, put it in a cell and show that it works.

One of the major challenges in the new study was figuring out how to knit short pieces of DNA together in a particular order to create a large genome. Through earlier experiments, the team had found that proteins in yeast cells could quickly assemble large pieces of DNA. "We were amazed that yeast has this capacity, so we tried to push the limits," Gibson says.


After going through three rounds of assembly in surrogate yeast cells with progressively bigger chunks of synthesized DNA, the researchers produced a genome of recordsetting size, clocking in at 1,077,947 DNA letters. This synthetic genome was then introduced into M. capricolum cells, which began to forget their own characteristics and instead adopt properties, including the protein profile, of the genome-donor species, M. mycoides.

"It's still pretty stunning to me that simply by changing the software in the cell, the cell immediately starts this process of converting into another species," says biologist J. Craig Venter. "It's all about how life works, how dynamic it is."

In most ways, the man-made genome was similar to the natural one, with a few important tweaks: The scientists added DNA sequences that the genome needs to survive the yeast-based assembly step and the transfer into its new cell. …