Artificial life comes a huge step closer

Where we had one, we now have six. The team that built the first synthetic yeast chromosome has added five more chromosomes to their repertoire, totalling roughly a third of the organism’s genome. It’s a dramatic scaling-up of our capabilities, opening the door to large-scale genomic engineering.

It was in 2014 that Jef Boeke, now at New York University Langone Medical Center in New York City, and his colleagues constructed a single yeast chromosome. They then replaced one of a living yeast cell’s natural chromosomes with it — the first time this had been done in more complex cells with a nucleus.

Boeke’s team has since edited the yeast’s entire genome — streamlining it and adding molecular labels to ease future work — before farming out the synthesis of the 16 rewritten chromosomes to an international consortium of geneticists and yeast biologists.

Each of the additional five chromosomes announced last week was assembled from pieces of 30,000 to 60,000 DNA letters. This allowed researchers to “debug” each section as they went, correcting for errors that had crept in during the editing process.

As a result of this careful debugging, yeast cells with the synthetic chromosomes grow just as quickly in the lab as normal, wild yeast, despite the wholesale alterations (Science, DOI: 10.1126/science.aaf4557).

Other researchers say the health of the modified yeast is remarkable. “It now sets the stage for the ultimate, which is putting all 16 synthetic chromosomes intoone cell,” says Dan Gibson at Synthetic Genomics, a biotech company in La Jolla, Calif. “Inow have more confidence that they’ll be able to achieve that.”

If and when they do, researchers hope to learn a huge amount. “If you take a bicycle and break it down to its smallest parts in your basement, and reassemble it again, you know a hell of a lot more about your bicycle than you did before,” says Boeke. Similarly, taking apart a genome and rebuilding it should yield new understanding of life and its processes.

A synthetic genome will also give bioengineers unprecedented control over yeast metabolism, which we already exploit to make chemicals such as drugs and perfumes. That would allow them to expand the range of molecules yeast can produce.

Researchers could also try inserting human versions of genes into yeasts, something they already do for a few genes at once. Synthetic chromosomes would allow them to go a great deal further — a big plus when it comes to testing new drugs.

But the biggest payoffs may be ones that no one foresees, says geneticist George Church at Harvard University.