#41: A Synthetic Genome Is Built From Scratch

The art of recreating an entire bacterial genome.

By Jocelyn Rice|Sunday, December 14, 2008

The quest to create life in the lab took a leap forward in February when scientists at the J. Craig Venter Institute (JCVI) announced in Science [subscription required] that they had synthesized an entire bacterial genome from scratch.

The JCVI team, led by Nobel Prize–winning biologist Hamilton Smith, began by synthesizing 101 fragments of the genome, each around 6,000 base pairs long. The team then used Escherichia coli bacteria to make many copies of each synthesized DNA snippet. Next the researchers patched the segments into longer pieces, using overlapping sequences to match up the fragments and checking after every step for mistakes.

By the time the strands surpassed 100,000 base pairs in length—more than three times the size of the largest piece of DNA previously synthesized—the host E. coli became overwhelmed and the scientists began to use yeast instead. Finally, at a whopping 582,970 base pairs, the genome was complete.

The synthetic genome was modeled after that of a tiny bacterium called Mycoplasma genitalium, carrying all the same genes in roughly the same order. To ensure that an organism with a man-made genome could never survive outside the laboratory, the scientists inserted a gene to make it dependent on an antibiotic. And to help them distinguish between the synthetic genome and its natural counterpart, they added a special watermark: their own names and that of the institute, spelled out in letters of the genetic code.

Lacking the biological machinery of a cell, the genome itself is not alive, but it should be possible to create full-blown artificial life by transplanting it into a cell—which is the researchers’ next step. “It’s a key aspect of understanding life, to be able to define it and build it,” JCVI president J. Craig Venter says.

The researchers plan to tweak the genome in tens of thousands of different ways to answer questions about what is needed for an organism to function properly. “There are a lot of things about very basic genomics that nobody knows the answer to yet,” Venter says.

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