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Scientists have created a living organism whose DNA is entirelymade by the man – Perhaps a new form of life, said the experts, and a milestone in the field of synthetic biology.
Researchers at the University of Cambridge announced Wednesday that they have rewritten the DNA of the bacterium Escherichia coli, creating a synthetic genome four times larger and much more complex than those previously created.
The bacteria are alive, but of unusual shape and reproduce slowly. But their cells function according to a new set of biological rules, producing proteins familiar with a reconstructed genetic code.
The achievement of one day can lead to organisms that produce new drugs or other valuable molecules, as living factories. These synthetic bacteria can also offer clues as to how the genetic code was created in the early days of life.
"It's a landmark," said Tom Ellis, director of the Synthetic Biology Center at Imperial College London, who did not participate in the new study. "No one has done anything like that in terms of size or number of changes before."
Each gene of a living genome is detailed in an alphabet of four bases, molecules named adenine, thymine, guanine and cytosine (often described only by their first letters: A, T, G, C). A gene can consist of thousands of bases.
Genes force cells to choose from 20 amino acids, the building blocks of proteins, the beasts of burden of each cell. Proteins exert a large number of tasks in the body, from the transport of oxygen in the blood to the generation of force in the muscles.
Nine years ago, researchers builds a synthetic genome of one million base pairs. The new genome of E. Coli, reported in the journal Nature, has a length of four million base pairs and had to be constructed with entirely new methods.
The new study was led by Jason Chin, a molecular biologist at the University of Cambridge in Britain, who wanted to understand why all living things code genetic information in the same confusing way.
The production of each amino acid in the cell is directed by three bases arranged in the strand of DNA. Each of these trios is called a codon. The TCT codon, for example, ensures that an amino acid called serine is attached to the end of a new protein.
Since there are only 20 amino acids, you will think that the genome only needs 20 codons to make them. But the genetic code is full of redundancies, for reasons that nobody understands.
Amino acids are coded by 61 codons, step 20. The production of serine, for example, is governed by six different codons. (Three other codons are called stop codons; they tell DNA where to stop the construction of an amino acid.)
Like many scientists, Dr. Chin was intrigued by all these duplications. Were all these pieces of DNA essential to life?
"Because life uses 64 codons universally, we really do not have an answer," said Dr. Chin. It was therefore decided to create an organization that could shed light on the issue.
After some preliminary experiments, he and his colleagues devised a modified version of the E genome. Coli on a computer requiring only 61 codons to produce all the amino acids that the body needs.
Instead of needing six codons to make serine, this genome only uses four. He had two stop codons, not three. Indeed, the researchers treated E. coli DNA as it was a gigantic text file, fulfilling a search and replacement function at more than 18,000 locations.
Now the researchers had a plan for a new genome of four million base pairs. They could synthesize DNA in the lab, but introducing it into the bacterium – essentially substituting synthetic genes for those derived from evolution – was a daunting challenge.
The genome was too long and complicated to be forced into a cell in one attempt. Instead, the researchers built small segments and exchanged them piece by piece in the E genome. Coli. By the time they were finished, there was no natural segment left
To their relief, modified E. coli is not dead. Bacteria grow more slowly than normal E. coli and develop longer rod-shaped cells. But they are very alive.
Dr. Chin hopes to build on this experience by removing more codons and further compressing the genetic code. He wants to see how the genetic code can be simplified while maintaining life.
The Cambridge team is just one of many competitions conducted in recent years to create synthetic genomes. The list of potential uses is long. An attractive possibility: viruses may not be able to invade recoded cells.
Many companies today use genetically modified microbes to make drugs such as insulin or useful chemicals such as detergent enzymes. If a viral outbreak strikes the fermentation tanks, the results can be catastrophic. A microbe containing synthetic DNA could be immunized against such attacks.
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DNA recoding could also allow scientists to program modified cells so that their genes do not work if they escape into other species. "This creates a genetic firewall," said Finn Stirling, a biologist of synthesis at Harvard Medical School, who did not participate in the new study.
Researchers are also interested in the recoding of life, as it opens up the possibility of making molecules with entirely new types of chemistry.
Beyond the 20 amino acids used by all living beings, there are hundreds of others. A compressed genetic code will release codons that scientists can use to code these new building blocks, creating new proteins that perform new tasks in the body.
James Kuo, a postdoctoral fellow at Harvard Medical School, has been cautious. Assembling bases to create genomes remains extremely expensive.
"It's way too expensive for university groups to continue," said Dr. Kuo.
But E. coli is a spearhead of laboratory research and it is now clear that its genome can be synthesized. It is not hard to imagine that prices will go down as demand for synthetic and custom DNA grows. Researchers could apply M. Chin's methods to yeast or other species.
"In theory, you can recod everything," Stirling said.
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