'Designer' chromosome for brewer's yeast built from scratch
Scientists streamlined organism's DNA and added sequences in first ever creation of an artificial 'eukaryotic' chromosome
Ian Sample, science correspondent
Thursday 27 March 2014 14.07 EDT
Researchers have built a complex chromosome from scratch and shown that it works normally by transplanting it into a healthy organism.
The international team used a computer to redesign one of the chromosomes found in brewer's yeast, recreating the thread-like structure piece by piece in the laboratory.
In a project that took seven years, the scientists streamlined the chromosome by removing non-essential genes and replacing them with fresh DNA to produce new strains of yeast.
The achievement demonstrates the progress being made in synthetic biology, a field that promises to give researchers unprecedented control over biological material.
Though scientists have previously built chromosomes for bacteria and viruses, this work is the first to create a chromosome for a more complex organism with a clearly defined nucleus. These "eukaryotes" include plants, animals and humans.
Research on artificial chromosomes could lead to the creation of organisms designed to churn out useful chemicals, drugs or biofuels.
The team – led by Jef Boeke of New York University's institute for systems genetics – recreated chromosome three in brewer's yeast, Saccharomyces cerevisiae. The chromosome, one of the smallest found in the strain, governs how well the organisms mate.
"This is a major step forward. It's the first synthetic eukaryote chromosome," said Patrick Yizhi Cai, a member of the team at Edinburgh University. "This really demonstrates that we can do rational design on the chromosome scale. Ten years from now we'll be able to synthesise genomes on a day-to-day basis."
The work is part of a global effort called Sc2.0 that aims to make all of the yeast's chromosomes from chemicals in the laboratory. To keep costs down, the researchers enlisted 60 undergraduates to do the synthesis.
Writing in the journal Science, the authors describe how yeast cells that carried the artificial chromosome, called synIII, grew as well as natural strains of yeast. "They behave almost identically to wild yeast cells, only they now possess new capabilities and can do things that wild yeast cannot," said Boeke.
To make the artificial chromosome, the students stitched together short strands of DNA to make longer stretches of 750 to 1,000 "letters" of DNA code. Using the scrambling process they had built into the chromosome, Boeke said they can shuffle the yeast's genome like a pack of cards. That could allow the rapid development of new strains of yeast for manufacturing drugs and vaccines.
"With this technology, we can re-engineer and customise organisms. We could make much sleeker genomes for organisms that would be useful for making biofuels and other industrial applications," Yizhi Cai said.
The enormous potential of synthetic biology has led to concerns that it might pose an environmental or public health threat if designer organisms were to escape from laboratories. To make the organisms safer, they can be designed to die outside the lab, for example by making them unable to replicate without an amino acid that is not found in nature.
"Now we have this powerful technology in hand, we need to be mindful of what we are doing," said Cai.