Scientists Swap Genes in Bacteria

Friday, June 29, 2007




Talk about identity theft: Scientists changed one species of bacteria into another by performing a complete gene swap.

It's a step in the quest to one day create artificial organisms, part of a bigger project to custom-design microbes that could produce cleaner fuels. But the way it was performed, dubbed a "genome transplant," has genetics specialists buzzing.

"This is equivalent to changing a Macintosh computer to a PC by inserting a new piece of software," declared genome-mapping pioneer J. Craig Venter, senior author of the new research published Thursday by the journal Science.

For years, scientists have moved single genes and even large chunks of DNA from one species to another. But Venter's team transplanted an entire genome, all of an organism's genes, from one bacterium into another in one fell swoop.

These weren't complex bacteria, but cousins from a family of small, simple microbes known as Mycoplasma. Nor do the researchers know exactly how the transplant took hold. But somehow the new genes cleanly replaced the old and started working correctly _ not very often, but in just enough cells to prove the concept.

The experiment "is a landmark in biological engineering," said Dr. Barbara Jasny, a deputy editor of Science.

Beyond pushing scientific boundaries, why would switching a goat germ into a cattle germ be useful?

That's not the real aim. It's part of a broader field called "synthetic biology" or "synthetic genomics" that aims to build new organisms that work in ways totally different than nature intended _ and scientists are divided about whether the Venter approach will really play a big role.

"There are people doing some important synthetic engineering efforts with other approaches," cautioned Dr. David Relman, a microbiologist and infectious disease specialist at Stanford University. "This is a different one that is a little more daring, and perhaps dramatic."

"One could wonder whether this method will be used for more than a tiny research community," added Dr. George Church, a genetics professor at Harvard Medical School. "Most people find it easier to work with pieces" of DNA.

Church points to the most popular synthetic biology method under study, genetically modifying existing organisms, such as E. coli bacteria, to make them do such things as churn out medications.

In contrast, Venter's self-named institute in Rockville, Md., is trying to create an artificial chromosome _ the structure that carries DNA _ that contains industrially useful genes such as ones that could help produce alternative fuels.

That work is far from complete, but to make it work, they'd have to put the artificial chromosome into a living cell and it would have to jump-start that host. Thursday's experiment was designed just to prove an entire-genome switch is possible, with regular bacteria DNA.

The Venter team picked two Mycoplasma species, simple germs that contain a single chromosome and lack the cell walls that form barriers in other bacteria. First, they added genes to turn the donor bacteria an easy-to-spot bright blue, and to make it resist an antibiotic used to kill off any host germ that retained its own genes.

Then they stripped off the donor chromosome's proteins, to see if naked DNA alone could "reboot" a foreign cell. Blue germs appeared within days of dropping the genome into lab dishes containing the second bacteria. Not many _ only about one in every 150,000 cells took up the donor genome and grew, but they bore no evidence of the original DNA.

"That's extremely inefficient," acknowledged lead scientist John Glass, a Venter Institute microbiologist. "We think we can steadily improve this."

"Synthetic genomics still remains to be proven, but now we are much closer to knowing it's actually theoretically possible," added Venter.

It's not clear that the method would work on larger, more complicated bacteria, other specialists cautioned. Nor does the work automatically mean an artificial chromosome alone could activate a living cell.

"It's going to be much more complicated to do with synthetic organisms," said Dr. Jonathan Eisen, an evolutionary biologist at the University of California, Davis. Still, "it's a great first step."

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