Scientists have made the first artificial chromosome which is both complete and functional in a milestone development in synthetic biology, which promises to revolutionise medical and industrial biotechnology in the coming century.
The researchers built the artificial chromosome from scratch by stitching synthetic strands of DNA together in a sequencebased on the known genome of brewer's yeast. They predict that a completely synthetic yeast genome comprising its entire complement of 16 chromosomes could be made within four years.
"Our research moves the needle in synthetic biology from theory to reality. This work represents the biggest step yet in an international effort to construct the full genome of synthetic yeast," said Dr Jef Boeke of the New York University School of Medicine, a lead author of the study published in the journal Science.
"It is the most extensively altered chromosome ever built. But the milestone that really counts is integrating it into a living yeast cell. We have shown that yeast cells carrying this synthetic chromosome are remarkably normal," Boeke said.
"They behave almost identically to wild yeast cells, only they now possess new capabilities and can do things that wild yeast cannot.
"Not only can we make designer changes on a computer, but we can make hundreds of changes through a chromosome and we can put that chromosome into yeast and have a yeast that looks, smells and behaves like a regular yeast, but this yeast is endowed with special properties that normal yeasts don't have."
The synthetic yeast chromosome was based on chromosome number 3, but scientists deleted large parts of it that were considered redundant and introduced further subtle changes to its sequence - yet the chromosome still functioned normally and replicated itself in living yeast cells, they said. "We took tiny snippets of synthetic DNA and fused them together in a complex series of steps to build an essentially computer-designed chromosome 3, one of the 16 chromosomes of yeast. We call it synIII because it's a completely synthetic derivative that has been engineered in a variety of interesting ways to make it different from the normal chromosome," Boeke said.
The achievement was compared to climbing Mt Everest in its labour-intensive complexity, as it involved stitching together 273,871 individual building blocks of DNA - the nucleotide bases of the yeast's genes - in the right order, and removing about 50,000 repeating sequences of the chromosome that were considered redundant.
"When you change the genome you're gambling. One wrong change can kill the cell. We have made over 50,000 changes to the DNA code in the chromosome and our yeast still lived.
"That is remarkable, it shows that our synthetic chromosome is hardy, and it endows the yeast with new properties," Boeke said.
