Bacteria genome switch-a-roo

Scientists have successfully forced a bacterium to switch species with another closely related species by replacing one genome with the other. This "transplantation" technique, spearheaded by J. Craig Venter and described in this week's Science, could insert synthetic genomes into cells to help create synthetic organisms, although Venter cautioned that the step is a long ways away. Venter and colleagues at the J. Craig Venter Institute in Rockville, Md., replaced the genome of Mycoplasma capricolum with that of a closely related bacterium, Mycoplasma mycoides. They used mycoplasma because this genus has a relatively small genome (roughly 1 million base pairs) and because it lacks cell walls, making it easier to insert bulky DNA molecules. Venter and his team suspended M. mycoides cells in agarose to protect the soon-to-be-naked donor DNA from jostling and breakage, and incubated it with enzymes to digest the cells' other components. After isolating the DNA, they incubated the donor genomes with host bacteria in a buffer containing polyethylene glycol (PEG), to promote DNA transfer. The M. mycoides genome carried a tetracycline resistance gene that allowed the researchers to later identify the transplant cells by screening with the antibiotic. Colonies that developed after three days were genetically identical to donor cells based on Southern blot analysis. The newly formed bacteria also carried surface antigens and cell proteins specific to M. mycoides. "We want to make sure the DNA itself can boot up the cell," Venter said in a press teleconference. If accessory proteins were also required, "that would be a huge barrier to the field of synthetic genomics. You would have to take a long time to sort out which proteins were necessary and have them at the right concentrations."Efficiency is still a concern, the authors wrote--the procedure worked just one in 150,000 times "in our most efficient experiments." John Glass, coauthor of the study, told The Scientist in an Email that the yield was still significant, with hundreds of colonies produced in each experiment. Applying this technique to higher organisms "is an extremely long way off, if ever," Venter said. Even simple bacterial cells contain specific restriction enzymes to protect them against invading DNA, he noted. "Adding DNA to each unique type of bacteria will require understanding their restriction systems. There's no universal formula for doing this."The researchers could not explain how the M. capricolum genomes disappear after transplantation. Venter speculated that after cell division, donor and recipient genomes separate into different daughter cells; when tetracycline is added to the mix, non-resistant M. capricolum are culled. However, coauthor Hamilton Smith said at the teleconference that their experiments suggested the donor genome might have a mechanism to cleave and destroy the recipient genome.Pamela Silver at Harvard, who did not participate in this study, told The Scientist in an Email, "This is an important step toward the Holy Grail of whole-genome engineering. But, she added, the final, most difficult step will be to design a genome with interesting and useful properties."Venter recently came under fire from Action Group on Erosion, Technology and Concentration (ETC Group), a technology watchdog group based in Ottawa, Canada, when they found he had filed a patent on a synthetic bacterium containing the barebones genome needed to power a cell. The group claimed he breached ethical boundaries by trying to patent a life-form. George Church at the Massachusetts Institute of Technology, also not a coauthor, said that the applications of the transplant technique were unclear. Venter et al's "related patent application says biofuels, but I'll be impressed if you can find someone who can explain how this enables biofuel research in a way not possible in other methods," Church said in an Email. Venter, however, was more optimistic. He noted that synthetic organisms with minimal genomes will be energetically more efficient than genetically modified organisms when it comes to biofuels and other applications, because modified cells have extraneous metabolic pathways, "shifting energy away from chemical synthesis."Charles Q. Choi mail@the-scientist.comLinks within this article:C. Lartigue et al. "Genome transplantation in bacteria: Changing one species to another," Science, published online ahead of print June 28, 2007. http://www.sciencemag.orgS. Pincock. "Venter buys history." The Scientist, August 29, 2005. http://www.the-scientist.com/article/display/15677J. Lucentini, "Is this life?" The Scientist, January 1, 2006. http://www.the-scientist.com/2006/1/1/30/1/John Glass http://www.jcvi.orgC. A. Hutchinson et. al., "The new biological synthesis," The Scientist, January 1, 2006. http://www.the-scientist.com/2006/1/1/38/1P Silver, "Cells by design," The Scientist, September 27, 2004. http://www.the-scientist.com/2004/9/27/30/1/C.Q. Choi, "DNA synthesis method yields 15-kb gene cluster", The Scientist, April 11, 2005. http://www.the-scientist.com/article/display/15402

Bacteria genome switch-a-roo

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