Science: Step Toward Synthetic Genomes

For the first time, researchers have replaced the whole genome of a bacterial cell with the genome of a closely related species. In a study published Thursday 28 June by the journal Science at its Science Express Web site, Carole Lartigue and colleagues describe how they transplanted the genome—in the form of naked DNA, virtually free of protein—and effectively turned one species of bacteria into another.

Once the donor genome had completely replaced the genome in the recipient bacterial cells, the recipient bacterial cells became identical in every way to the donor bacterial cells, the researchers found.

"This is equivalent to changing a Macintosh computer to a PC by inserting a new piece of software. This is the biological equivalent," said co-author J. Craig Venter during a Wednesday teleconference with reporters.

The research team hopes to use this "transplantation" procedure to someday build a simple genome from scratch and insert it into a living cell. Scientists could then create synthetic genomes with an eye toward developing microorganisms that produce new types of biofuels, clean up toxic waste, sequester carbon, or other applications.

Venter described the study as "a key enabling step" in the field of synthetic genomics, saying, "once we have a synthetic chromosome, we now know it is possible to boot that up."

In nature, bits of DNA can sometimes shuttle between species, and researchers have been able to insert increasingly large chunks of genetic material into new cells. But the study in Science is the first to show that an entire genome, devoid of its usual protein wrappings, can be moved intact into a new cell and go to work without a hitch.

Lartigue and colleagues at the J. Craig Venter Institute created a donor genome by carefully removing the proteins and other surrounding molecules from a Mycoplasma mycoides chromosome, eventually revealing its naked DNA like a sculptor chiseling away at a marble block to reveal a shape.

The Mycoplasma mycoides DNA, containing antibiotic-resistant genes inserted by the scientists, was mixed with cells of Mycoplasma capricolum and exposed to the antibiotic tetracycline. The result was a new generation of cells with the genome and the physical attributes of mycoidesbacteria.

The researchers suspect that the antibiotic kills off the capricolum genome and paves the way for the mycoides DNA, but they are still not sure exactly how the transplantation occurs. So far, the procedure only results in one successful transplant in about 150,000 cells.

Kathy Wren and Becky Ham

28 June 2007