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Genome Discovery Holds Key to Designer Organisms

Scientists are homing in on the fewest genes needed for an organism to survive.

For more than 20 years, J. Craig Venter has been trying to make a cell with the fewest possible genes in the hope that the stripped-down cell would tell us something about the necessities of life.

In a paper published today in Science, Venter and his team announced that they’ve made a big step toward that goal—and found some surprises along the way.

The parts list of basic life is one-third longer than scientists had thought, said Venter, who is known for winning the race to map the human genome. And it depends much more on context than they had realized.

Getting their synthetic cell to replicate and grow fast enough to use in the lab took 473 genes, 149 of which have an unclear function.

Venter, founder, chairman, and CEO of the J. Craig Venter Institute, which led the research, said he started his hunt assuming he’d be able to pinpoint the single or few genes responsible for this or that trait. Instead, he said at a Wednesday news conference, he’s learned that functions, diseases, and basic existence are dependent on the interplay of many genes.

“Life is much more like a symphony orchestra than a piccolo player,” he said.

Most of the applications for this synthetic cell are years or decades off, but it is an important scientific advance.

A cluster of synthetic cells with the fewest genes needed to grow and divide. In cultures, these so-called JCVI-syn.30 cells form a variety of structures.

“This is really useful for giving you an insight to what’s really the minimal parts list it takes to keep an organism going,” said Jef Boeke, director of the Institute for Systems Genetics at New York University’s Langone Medical Center. “There’s tremendous value in terms of understanding the basic wiring of a cell.”

The synthetic cell, dubbed JCVI-syn3.0, also has potential applications for advancing medicine, nutrition, agriculture, biofuels, and biochemicals, said Dan Gibson, vice president of DNA Technology for Synthetic Genomics, a company started by Venter to commercialize genetic advances, which was also involved in the new work.

“Our long-term vision is to have the ability to design and build synthetic organisms on demand that perform specific functions that are programmed into the cellular genome,” Gibson wrote in a follow-up e-mail. Synthetic cells with a minimal parts list “would be devoting maximal energy to their purpose—they would simply grow and divide and make the product that was programmed into the cell.”

When asked for specific examples of applications, Venter mentioned synthetic antibiotics and an ongoing collaboration between Synthetic Genomics and United Therapeutics to grow transplantable organs in pigs. Humans cannot use pig hearts, lungs, or livers because of the risk of rejection and diseases, but the companies are trying to engineer changes into the pig genome to make that possible.

Harvard University geneticist George Church prefers to edit functions into existing genomes, rather than build up from the bottom. Church said JCVI-syn3.0 is a significant academic achievement, but he doesn’t see much practical use for it in the short -term.

“I don’t want to be impolite,” Church said. “I think it’s a lovely thing they did.”

As a scientific feat, Church said, he was more impressed with the group’s earlier work done more than five years ago, which showed that the team could synthesize a much larger genome that is much closer to the complexity needed for real-world applications.

Venter said the work shows how far we still have to go to understand the genomes of even the simplest creatures. 

“The fact that this has taken a highly dedicated, extremely competent team with a Nobel laureate, three National Academy of Science members, and some brilliant junior scientists this long to get this far tells us a lot about the fundamentals of life and says the next phases are not going to be trivial,” he said.

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