Synthetic Genome Reboots Cell

A genome built from scratch is a step toward synthesizing novel organisms.

In the culmination of a project spanning 15 years, scientists at the J. Craig Venter Institute have engineered the first cell controlled by a synthetic genome.

Starting from scratch: Scientists rebooted bacterial cells by transplanting a synthetic version of the Mycoplasma mycoides genome manufactured in the lab. The synthetic genome includes a marker gene that makes a blue compound, so the synthetic cells form blue colonies (top). The naturally occurring M. mycoides genome lacks that gene, so the wild-type cells form white colonies (bottom). Credit: Science/AAAS

"This is the first time that the information of a genome sequence has been turned back into life," says Chris Voigt, a synthetic biologist at the University of California, San Francisco, who was not involved in the project. "It's really remarkable."

Using a method developed in 2008, the researchers, led by genomics pioneer Craig Venter, synthesized the genome of a tiny bacterium called Mycoplasma mycoides, containing just over a million DNA base pairs. Next they transplanted the synthetic genome into a related bacterium, Mycoplasma capricolum, in a process they had previously perfected using nonsynthetic chromosomes.

Once the recipient cells incorporated the synthetic genome, they immediately began to carry out the instructions encoded within the genome. The cells manufactured only M. mycoides proteins, and within a few rounds of self-replication, all traces of the recipient species were gone. The results were published Thursday in the online edition of the journal Science.

To distinguish their synthetic genome from the naturally occurring version, the researchers encoded a series of watermarks into the sequence. They began by developing a code for writing the English alphabet, as well as punctuation and numbers, into the language of DNA--a decoding key is included in the sequence itself. Then they wrote in their names, a few quotations, and the address for a website people can visit if they successfully crack the code.

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In terms of creating synthetic life, this project is a proof of principle: aside from the watermarks and a handful of gene deletions to reduce the species' ability to cause disease, the synthetic genome essentially recreates a naturally occurring one. Venter hopes that in the future, the synthetic genomic technology can be used to design and develop entirely new organisms, with wide-ranging practical applications.

Venter and his colleagues are working with Novartis and the National Institutes of Health to synthesize cassettes--clusters of genes that could be inserted into a synthetic genome--for every known flu virus in an effort to streamline the vaccine manufacturing process. They envision a system where, if a new strain such as H1N1 emerged, developing a vaccine would be as straightforward as shuffling genes encoding the relevant viral fragments into a synthetic genome. This could then yield a cell that could be used to quickly manufacture the product.