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Replacing a Genome Boosts Race to Develop Designer Bugs: Study

Researchers transformed one bacterial species into another by swapping their genomes, a move that will accelerate the race to develop custom-built synthetic bugs, a pioneer on genetics said Thursday.

Craig Venter, who had a hand in mapping the human genome, said a team of his researchers had transplanted the entire genetic code of one bacterial organism into another closely related species.

The experiment marks the most ambitious attempt yet to re-engineer a living cell with a view to one day developing microorganisms that could be used for biofuels, cleaning up toxic waste, sequestering carbon or other applications.

It "is a landmark in biological engineering taking us from moving one gene or a set of genes to the ability to move an intact genome," said Barbara Jasny, deputy editor of the journal Science, which first reported the experiment in this week's issue.

For decades, molecular biologists have genetically modified microbes and other kinds of cells by adding short DNA sequences, whole genes and even large pieces of chromosomes in their quest to fashion synthetic bugs that can make anti-malaria drugs or novel biofuels.

But this is the first time that researchers have transplanted an entire genome into a living organism and shown that the cell can express the foreign DNA.

"This is equivalent to changing a Macintosh computer to a PC by inserting a new piece of software," Venter said.

It's a "landmark in biological engineering," said Barbara Jasny, deputy editor of the journal Science, which first reported the experiment in this week's issue.

The experiment shows for the first time that it is possible to insert an intact genome into a host organism and have that organism express the foreign DNA. The next step is to create a synthetic genome and transplant that into a host organism.

"It's a key enabling step," said Venter. "Synthetic biolo gy still remains to be proven, but now we are much closer to knowing it's absolutely theoretically possible."

In this experiment, the scientists at the J. Craig Venter Institute in Rockville, Maryland, used naturally-occurring DNA from a living organism, but they believe the transplantation techniques could be used on artificial, or man-made genomes, once they are developed.

To that end, they are seeking patents on the methods they used in this study.

The researchers took the genome of a simple, one-celled organism called Mycoplasma mycoides and transplanted it into a close relative, M. capricolum.

Both of these bacteria, which are innocuous goat pathogens, lack an outer membrane, facilitating genome transfer.

Before transplantation, the researchers modified the DNA of the donor bacteria, adding two genes that would provide proof if the transfer had worked. One gene conferred antibiotic resistance, the other caused bacteria expressing it to turn blue.

The enhanced Mycoplasma mycoides genome was added to a test-tube of M. capricolum, and the contents of the tube were exposed to an antibiotic.

Within four days blue colonies appeared, indicating that the host organisms had taken up the foreign DNA.

When the team analyzed the blue bacteria for DNA sequences specific to either mycoplasma, it found no evidence of the host bacteria's genetic material.

Many questions still remain. The researchers acknowledged that they were not sure how the one genome displaced the other.

"We don't know for certain how the donor genome takes over," Hamilton Smith, a lead author on the paper, told a teleconference.

The process is also "extremely inefficient" with a success rate of one in 150,000, said John Glass, a lead author on the paper.

Still, Venter said this proof of concept is likely to speed research in this emerging d iscipline, yielding new developments in months, instead of years as was previously the case.


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