The Mysterious Thing About a Marvelous New Synthetic Cell – The Atlantic

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“We set out relatively certain that we could design a cell from scratch,” says Venter. “We were so cocky that we even had a contest between ourselves to see who could do it first.”

They started with Synthia’s genome and deleted 440 seemingly disposable genes, leaving just 432. Once again, they synthesized this set and transplanted it into an empty cell. Which promptly died. “Nothing worked,” says Venter. “We couldn’t get a living cell. It became clear that all those earlier studies were missing something fundamental.”

There were two big problems. The first is clear in hindsight: there are many essential genes that no one knew anything about. The second became obvious earlier: many genes are redundant. The team had been judging the worth of genes by hobbling them one by one and seeing if cells still survived. But many pairs of genes understudy for each other: losing one is no big deal but losing both is catastrophic. Put it this way: knock out either engine on a jumbo jet, and it’ll probably still fly; bill them both as “non-essential” and your plane will crash.

Figuring out these redundancies took a lot of time, especially since many of them involved unknown genes. The JCVI team carried out several cycles of designing, building, and testing, restoring important genes that had been unadvisedly removed and removing more that actually were dispensable. After a few years, they got their first viable cell, which they called syn2.0. It has 516 genes, just nine fewer than M.genitalium. “It wasn’t a moment of celebration,” says Venter. “It was more relief. It told us that we hadn’t done something stupid.”

They finally jettisoned 43 more genes to arrive at syn3.0—their “working approximation of a minimal cell,” with just 473 genes.

Are these “essential”? It depends.“Essentiality is based on the environment,” says Venter. “That’s why we talk about a minimal genome, not the minimal genome.” A microbe growing in a hot volcanic spring needs very different genes to one growing in your gut. And many bacteria live only inside the cells of insects and other animals. Within these constant, closeted environments, the microbes can afford to lose genes that they would otherwise need for a free-living existence. The smallest of them, Nasuia, has just 137.

So there’s minimal, and there’s minimal. Syn3.0 represents the former—something close to the bare set of genes needed for independent life. It can live on some basic nutrients, grow at a reasonable pace, and reproduce on its own. “I think it is difficult—near impossible—to define a minimal genome, but this paper takes us awfully close,” adds Farren Isaacs from Yale University. “It’s an impressive tour de force.”

The Mysterious Thing About a Marvelous New Synthetic Cell – The Atlantic