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Venter Institute Team Demonstrates Successful Cross-Species Genome Transfer

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A research team at the J. Craig Venter Institute recently completed work that promises to seriously ramp up synthetic genomics and bring the concept of a synthetic cell that much closer to reality.

So far, the scientists have demonstrated a method of transferring genomes between a prokaryote to a eukaryote and back again. Using yeast cells with an added dose of yeast centromeric plasmid sequence, the JCVI team cloned the whole bacterial genome from Mycoplasma mycoides, modified the bacterial chromosome using the yeast's own genetic systems, and followed that up by transplanting the new genome into the related species Mycoplasma capricolum. The end result was a new type of mycodies cell never before seen in nature or in a laboratory.

"Mycoplasmas in general do not have very robust genetic tools — or hardly any genetic tools, so you can't easily add or delete genes. But we can use the nice set of tools that yeast has to manipulate the [mycoides] genome," says Sanjay Vashee, a JCVI researcher who contributed to the project. "The implications here are several-fold, but one is that we've overcome a barrier that we needed to deal with for the genome to be 'booted up' — this allows us to get a step closer to the synthetic cell."

The barrier that had -previously prevented the installation of a modified genome had to do with the restriction enzymes that act as an immune system to help bacteria defend itself against invading DNA.

The researchers first devised a method of removing that immune system from the recipient cell so that the incoming genome would not be chewed up.

The second method was to use in vitro chemical modification with purified methylases that would install a protective methyl group on the genome, thereby overcoming the restriction enzyme barrier from the recipient cell.

Vashee says that JCVI scientists are currently attempting to boot up their synthetic organism, Mycoplasma genitalium, so that they can eventually whittle away its genome to produce a "minimal cell" — a useful model system that has only the genes absolutely necessary for life.

They also hope that these methods can be utilized to help engineer bioenergy sources and industrial chemicals.

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