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Synthetic DNA added to yeast cells, paving way for 'evolution' on demand

Scientists' feat could lead to better biofuels and vaccines, and is a significant step towards completely synthetic organisms

    Brewer's yeast
    Synthetic DNA designed in the laboratory was added to yeast cells without preventing its ability to survive and reproduce. Photograph: Manfred Kage/Getty

    Life forms have been created that carry strands of genetic material designed and built from scratch in the lab, paving the way for on-demand "evolution" of organisms.

    Scientists made sections of chromosomes, the long molecules that bear DNA, and transferred them into yeast cells, of the kind normally used in baking.

    The cells adopted the new genetic code as part of their normal cellular machinery and, to the scientists' surprise, appeared as healthy as their natural counterparts.

    The feat is a big step towards the manufacture of completely synthetic organisms that could be designed to churn out biofuels, vaccines and industrial chemicals, said Jef Boeke, who led the study at Johns Hopkins University in Maryland.

    Studies of bugs with synthetic DNA are widely anticipated to shed light on some of the toughest questions in biology, such as what is the minimal suite of genes required for life on Earth.

    "We have created a research tool that not only lets us learn more about yeast biology, but also holds out the possibility of someday designing genomes for specific purposes, like making new vaccines or medications," said Jef Boeke, who led the study at Johns Hopkins University in Maryland.

    Built into the synthetic chromosomes are genetic sequences that, when triggered by a chemical, dramatically rearrange the organism's genes. The technique, known as genome scrambling, allows scientists to accelerate the evolution of the organisms on demand, by creating thousands of new strains and collecting the best survivors.

    The advance was made possible by powerful techniques that have emerged from rapid developments in genetics, computing and synthetic chemistry.

    Boeke's work centred on a yeast known as Saccharomyces cerevisiae, one of the most well-understood organisms in the field of genetics. It has 16 chromosomes that together carry around 6000 genes.

    The team started with a digital version of one yeast chromosome, which they edited on a computer according to three simple rules. These required the scientists to streamline the chromosome by removing non-essential genes without compromising the organism's fitness. Further sections of genetic code were then written into the chromosome to allow scientists to rearrange the genes in future experiments.

    Once the first chromosome was finalised, Boeke's team took a second chromosome and edited that in a similar way.

    In the next stage of the experiment, Boeke's team used feedstocks of chemicals to manufacture the new chromosomes from scratch. They then dropped these into growing colonies of yeast cells, which replaced parts of their natural chromosomes with the synthetic versions.

    The yeast cells' genetic makeover was modest, amounting to changes in only one percent of the organism's entire genome, but Boeke was still intrigued to see the organisms thrive.

    "They are remarkably healthy and to us that's incredibly exciting because it means our design is sound and we can play all the games we are fantasising about," Boeke told the Guardian. The study is reported in the journal, Nature.

    Boeke has recently developed more advanced methods for designing chromosomes but for these experiments, the work involved hours of meticulous editing on the computer. "It was unbelieveably tedious and it's almost a miracle the yeasts grows, because the potential for errors that could have occured is prodigious," he said.

    To see what happened when the yeast cells jumbled their genetic code, Boeke added a chemical that yeast does not normally come into contact with — the female sex hormone, oestrogen. This caused wholesale rearrangements of the organisms' genes, but also removed some genes entirely.

    "After scrambling, it's a very different story," said Boeke. "Most of the yeast are dead, there are a lot of essential genes missing and there are a lot of sick puppies in there that aren't as fit as natural yeast."

    Ultimately, the process of rearranging and deleting genes from the yeast cells should produce strains that survive with the bare minimum set of genes needed to sustain life, Boeke said.

    But the process has more practical implications, by allowing scientists to direct the evolution of yeast cells, until they are better than those in use by industry.

    "Man and yeast have this ancient relationship. We've been brewing beer and making bread since before the written word," said Boeke. "Nowadays, a major share of fermentation is done using yeast, and that's everything from making vaccines to chemicals and biofuel production.

    "All of those industries are actively looking for yeast that makes their favourite product better, whether it's more efficiently, with a higher yield, or in special conditions.

    "Industrial geneticists are always looking for new tools for their toolbox and this will become an important part of that."

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