Era of designer plants and animals edges closer with creation of synthetic yeast

| April 3, 2014
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This article or excerpt is included in the GLP’s daily curated selection of ideologically diverse news, opinion and analysis of biotechnology innovation.

Yeast and humans don’t seem to have much in common, but compared to bacteria and viruses, yeast look like second cousins. That’s why news that scientists have created a synthetic chromosome in yeast and it has replicated for generations is a big deal.

That fungi and people are closely related may not be obvious to the average human being. But biologically it is true, because both are eukaryotes, meaning that they have proper cell nuclei with several linear chromosomes in them, and also lots of other complex and well-defined cellular structures, called organelles. Bacteria, in contrast, are prokaryotes—meaning their DNA is arranged in small, circular chromosomes which float around in more or less organelleless cells.

A chromosome is a long strand of DNA. We have 23, yeast have 16. Eukaryotic chromosomes range from hundreds of thousands to millions of base pairs long, so there was a lot of leg work involved in the study. Jef Boeke and his international team, first built the chromosome in DNA modeling software, then built the chromosome into a series of nearly 273,000 base pairs using a DNA synthesis machine.

But, Boeke’s team didn’t just copy this chromosome as they found it, they ‘redesigned it’ according to Farren Isaacs, a bioengineer at Yale University. He told Nature:

“You can see that they are systematically paving the way for a new era of biology based on the redesign of genomes.”

Their redesign made the chromosome more efficient and stable by eliminating transposons and introns, chunks of DNA that don’t add to cell function. They also clipped genes for transfer RNAs because these spots can be unstable, and the genome has copies elsewhere for the organism to rely on.

But they also added in some instability in order to make the chromosome experimentally useful. Boeke added 98 loxPsym sequences to the DNA. These are like page markers pointing to interesting genes, and can be used to easily cut those genes out of the chromosome. According to the Economist:

This is part of a plan to find out which genes are necessary to yeast’s survival, and which merely desirable, by knocking them out. Until now, that has had to be done one gene at a time. Using a synthetic chromosome modified in this way means it will be easier to execute multiple, simultaneous gene knockouts.

And they’ve set it up to experimentally explore new ideas like making novel amino acids that aren’t produced in nature. Amino acids are the chemicals that, when strung together, create all the proteins in the world. There are 20 now, and Boeke’s team think they could design their chromosome to produce the 21st. This would be the equivalent of adding a new, stable element to the periodic table.

All of this tinkering could have made the chromosome more unstable, but it didn’t. From the Economist:

All these changes risk destabilising the new chromosome. But that does not seem to have happened. The team have run it through 125 generations in 30 different sets of yeast without it coming to any apparent harm. They thus seem to have created a robust demonstration that a synthetic eukaryotic chromosome can work.

Boeke plans to keep building the 15 remaining yeast chromosomes until he has created yeast with an entirely synthetic genome. Being able to design these chromosomes and genes could have big impacts on industry, pushing yeasts’ productive aspects past ethanol into other important compounds.

Of course this innovation comes with some intriguing ethical issues. The Economist sums it up:

In the longer term, other eukaryotes will no doubt be treated likewise. The day of designer plants and animals, then, is getting closer. And so too, for those who worry about such things, is the day when designer humans might be possible.

The GLP featured this article to reflect the diversity of news, opinion and analysis. The viewpoint is the author’s own. The GLP’s goal is to stimulate constructive discourse on challenging science issues.

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