We Are One Step Closer to Synthetic Life with Designer Chromosomes
Three years ago a team of scientists built the first synthetic yeast chromosome, and today they have got one giant step closer to their goal of creating a complex organism.
They have managed to add five more chromosomes, with a genome designed and built from scratch in the laboratory, writes New Scientist. This is a dramatic scaling-up of our capabilities and opens the door to large-scale genomic engineering. The world has already been treated to one synthetic genome, that of the bacterium nicknamed Synthia. However, bacteria have much smaller and simpler genomes than higher organisms, such as yeast and humans, known as eukaryotes. Synthesising a eukaryotic genome is, therefore, a much more complex challenge.
Jef Boeke, who led the team that originally managed to construct a single yeast chromosome. This week, that same consortium revealed the completion of an additional five chromosomes. Each one was assembled from pieces of 30,000 to 60,000 DNA letters. This allowed the builders to “debug” each section as they added it, correcting for inadvertent errors that crept in during the editing process.
As a result of the debugging, yeast cells with the new synthetic chromosomes grow just as quickly as normal, wild, yeast in laboratory cultures, despite the wholesale alterations. “It is amazing how much torture the yeast genome can take and still be happy and healthy,” said Boeke.
Others are very impressed with the health of the modified yeast. “The fact that they were able to do this across five different chromosomes, and the fitness is still familiar to wild-type cells, that’s pretty impressive,” explained Dan Gibson at Synthetic Genomics, a biotech company in La Jolla, California, which is developing synthetic chromosomes in another yeast species.
“It now sets the stage for the ultimate, which is putting all 16 synthetic chromosomes into one cell,” said Gibson. “I now have more confidence that they’ll be able to achieve that.” If and when this time comes, researchers are hoping 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,” added Boeke. Just like taking apart the entire genome and rebuilding it should yield new understanding of life and its processes. Not only this, but the biotechnology industry should also see large payoffs. Yeasts are already biotech workhorses, producing products such as pharmaceuticals and even perfumes in vase fermenting vats.
A synthetic genome will give bioengineers unprecedented control over yeast metabolism. For example, it would allow them to expand yeast’s repertoire of molecules to be produced or degraded. In addition, researchers could also “humanise” the yeast by incorporating human versions of genes. Although geneticists already do this for a few genes at once, synthetic chromosomes would allow them to delve much deeper, which is a big plus when it comes to testing new drugs and other therapies.
However, some of the biggest payoffs will be ones that no one foresees. “The history of genomics is you do what you can do, and then you rationalise that that’s all you wanted,” said George Church. Once more is possible, we’ll probably think of new things to do, he added.
Being given the opportunity to free the shackles of natural genomes, synthetic biologists may find that they want a whole lot more.