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Scientists build 'designer' chromosome
by Staff Writers
Paris (AFP) March 28, 2014


Scientists say they have built the first synthetic chromosome for a complex-celled organism after a seven-year effort, a step towards man-made genomes that some hailed on Friday but others viewed warily.

The artificial chromosome was inserted into a brewer's yeast cell, which continued to function as normal -- the ultimate test of success, an international research team reported in the journal Science.

"Our research moves the needle in synthetic biology from theory to reality," said Jef Boeke, director of the New York University's Institute for Systems Genetics, who led the project.

Fellow researchers hailed the lab creation of a chromosome with 273,871 base pairs of DNA as a breakthrough in the field of synthetic biology, while some flagged potential ethical quandaries.

"If the technology is used for sustainable production or production of medicines... then I think a lot of people would applaud it, but not if it would be used for simply Frankenstein reasons," said biotechnology professor Patricia Osseweijer of the Delft University in the Netherlands.

Yeast is a closely-studied representative of the group of eukaryotes, organisms with complex cells that contain a nucleus enclosed within a membrane.

All plants and animals, including humans, have eukaryotic cells.

Chromosomes have previously been synthesised for bacteria, which are simpler, prokaryotic organisms.

Yeast is used to make bread, beer, biofuel and antibiotics, and researchers believe it can be made to work more efficiently with genetic modifications.

Boeke and his team unravelled the coding of one of yeast's 16 chromosomes, then used software to change it -- removing repetitive and less-used parts.

They then built a synthetic version from scratch, stringing together individual nucleotides -- the chemical building blocks of the genes that make up chromosomes, which in turn comprise the genome.

"It is the most extensively altered chromosome ever built," said Boeke.

"We have made over 50,000 changes to the DNA code in the chromosome and our yeast is still alive. That is remarkable."

Yeast shares about a third of its 6,000 genes -- units of the chromosome that carry instructions for cell function -- with humans, who have 23 pairs of chromosomes.

Boeke and his team are already working on synthesising other yeast chromosomes as part of a larger project to construct an entirely synthetic yeast genome.

The project, they wrote, "represents a major step towards the design and complete synthesis" of a eukaryotic genome.

- Engineered genomes -

"Rapid advances in synthetic biology coupled with ever decreasing costs of DNA synthesis suggest that it will soon become feasible to engineer new eukaryotic genomes, including plant and animal genomes with synthetic chromosomes encoding desired functions and... properties based on specific design principles," said the study.

Tom Ellis, a synthetic biologist from Imperial College London who is involved in a separate synthetic yeast study, said Boeke's team had made a "very big step".

"People always feel that if humans are working with changing life forms like organisms, that they are somehow playing god or doing something risky," he said.

"But the yeast we work with is something humans have been working with to purposely evolve to be better and better at alcohol production" over hundreds of years.

Osseweijer said the achievement is likely to awaken the fears and concerns of people who are opposed to such bioengineering, and said it may be time for ethical guidelines to be reassessed.

"I would think that it would take ages before we can make a synthetic human being but nevertheless it is good to think about it," she told AFP.

"One has to be careful in how these kinds of things are governed because we want to prevent wrong use of this technology."

The baker's yeast genome comprises 12 million nucleotides, of which the synthetic chromosome comprised more than 2.5 percent.

Greenpeace scientist Janet Cotter said genetically modified organisms could be useful, in drug development for instance, but in controlled conditions.

"In a commercial situation, on a scale say for biofuels, then you run into problems about how you adequately and securely contain those organisms."

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