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Scientists build first synthetic yeast
chromosome
Thu, Mar 27 2014
By Julie Steenhuysen
CHICAGO (Reuters) - An international team of scientists has built a modified yeast chromosome from scratch, the latest
step in the quest to make the world's first synthetic yeast genome, an advance that would lead to new strains of the
organism to help produce industrial chemicals, medicines and biofuels.
Instead of just copying nature, the team did extensive tinkering with their chromosome, deleting unwanted genes here
and there. It then successfully incorporated the designer chromosome into living yeast cells, endowing them with new
capabilities not found in naturally occurring yeast.
"It is the most extensively altered chromosome ever built," said Jef Boeke of New York University's Langone Medical
Center, who led the effort. The findings were published on Thursday in an online edition of the journal Science.
While other teams have synthesized bacterium and viral DNA, Boeke's is the first report of a synthetic chromosome in a
eukaryote, an organism whose cells contain a nucleus, like human cells.
The achievement, which took seven years, involved the use of computer-aided design to construct one of 16
chromosomes in brewer's yeast, known scientifically as Saccharomyces cerevisiae.
The synthetic version, which the scientists call synIII, is a slimmed-down version of the yeast's naturally occurring
chromosome III, which has 316,667 base pairs. The team picked this chromosome because it is the smallest and
controls how yeast cells mate and undergo genetic change.
"We have shown that yeast cells carrying this synthetic chromosome are remarkably normal. They behave almost
identically to wild yeast cells, only they now possess new capabilities and can do things that wild yeast cannot," said
Boeke. Such methods could be used to improve yeast's ability to thrive in harsh environments, such as very high
concentrations of alcohol.
Boeke, formerly of Johns Hopkins University, joined NYU in January to head the newly formed Institute for Systems
Genetics.
Jim Collins of Boston University and a pioneer in the field called Boeke's work a "tour-de-force in synthetic biology," an
emerging field of science which applies the principles of engineering to living systems.
"This development enables new experiments on genome evolution and highlights our ever-expanding ability to modify
and engineer DNA," said Collins, whose lab won a Gates Foundation grant in 2012 to engineer a probiotic yogurt
bacterium to neutralize cholera infections.
Synthetic biology is best known for work done by genome scientist and entrepreneur Craig Venter, who in 2010 reported
he had built the first synthetic genome of a bacterium out of chemicals.
That work generated a lot of hype and considerable worry that scientists were tinkering with nature. Boeke said the work
in his lab and many others is much less like "playing God" and more akin to genetic engineering, but on a broader
scale.
CHROMOSOME SCRAMBLING
For their designer yeast chromosome, Boeke and his team made more than 500 changes, removing repeating sections
of nearly 50,000 base pairs of DNA they deemed unnecessary to chromosome reproduction and growth.
They also removed what has been called "junk DNA" - parts of the genetic code that do not make proteins - and
segments known as "jumping genes," stretches of DNA that randomly hop around the genome and can cause
mutations.
Despite all of those changes, Boeke said, "we still have a chromosome that works."
He is most excited about the ability to selectively delete or rearrange the letters of the chromosome, a process he calls
chromosome scrambling. To make this happen, the scientists added in stretches of DNA known as loxP, a gene
sequence that works as a genetic switch that can be activated by a protein.
"What's really exciting is in addition to yeast being healthy and happy, we've also endowed this chromosome with this
almost magical property of being able to rearrange its structure when we wave our magic wand and generate millions of
variant chromosomes," Boeke said.
Having the ability to produce new synthetic strains of yeast could result in some very useful types of yeast that could be
