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Full Version: "Evolution Machine": Genetic Engineering on Fast Forward
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Automated genetic tinkering is just the start – this machine could be used to rewrite the language of life and create new species of humans

IT IS a strange combination of clumsiness and beauty. Sitting on a cheap-looking worktop is a motley ensemble of flasks, trays and tubes squeezed onto a home-made frame. Arrays of empty pipette tips wait expectantly. Bunches of black and grey wires adorn its corners. On the top, robotic arms slide purposefully back and forth along metal tracks, dropping liquids from one compartment to another in an intricately choreographed dance. Inside, bacteria are shunted through slim plastic tubes, and alternately coddled, chilled and electrocuted. The whole assembly is about a metre and a half across, and controlled by an ordinary computer.

Say hello to the evolution machine. It can achieve in days what takes genetic engineers years. So far it is just a prototype, but if its proponents are to be believed, future versions could revolutionise biology, allowing us to evolve new organisms or rewrite whole genomes with ease. It might even transform humanity itself.

These days everything from your food and clothes to the medicines you take may well come from genetically modified plants or bacteria. The first generation of engineered organisms has been a huge hit with farmers and manufacturers - if not consumers. And this is just the start. So far organisms have only been changed in relatively crude and simple ways, often involving just one or two genes. To achieve their grander ambitions, such as creating algae capable of churning out fuel for cars, genetic engineers are now trying to make far more sweeping changes....
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The first "evolution machine" was built by Harris Wang, a graduate student in Church's lab. To prove it worked, he started with a strain of the E. coli bacterium that produced small quantities of lycopene, the pigment that makes tomatoes red. The strain was also modified to produce some viral enzymes. Next, he synthesised 50,000 DNA strands with sequences that almost matched parts of the 24 genes involved in lycopene production, but with a range of variations that he hoped would affect the amount of lycopene produced. The DNA and the bacteria were then put into the evolution machine.

The machine let the E. coli multiply, mixed them with the DNA strands, and applied an electric shock to open up the bacterial cells and let the DNA get inside. There, some of the added DNA was swapped with the matching target sequences in the cells' genomes. This process, called homologous recombination, is usually very rare, which is where the viral enzymes come in. They trick cells into treating the added DNA as its own, greatly increasing the chance of homologous recombination.

The effect was to create new variants of the targeted genes while leaving the rest of the genome untouched. It was unlikely that all 24 genes would be altered simultaneously in any one bacterium, so the cycle was repeated over and over to increase the proportion of cells with mutations in all 24 genes...
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This is not as alarming as it might sound. Because all existing life uses essentially the same genetic code, organisms that translate DNA using a different code would be behind a "genetic firewall", unable to swap DNA with any normal living thing. If they escaped into the wild, they would not be able to spread any engineered components. Nor would they be able to receive any genes from natural bacteria that would endow them with antibiotic resistance or the ability to make toxins. "Any new DNA coming in or any DNA coming out doesn't work," says Church. "We're hoping that people who are concerned, including us, about escape from industrial processes, will find these safer."

There is another huge advantage: organisms with an altered genetic code would be immune to viruses, which rely on the protein-making machinery of the cells they infect to make copies of themselves. In a cell that uses a different genetic code, the viral blueprints will be mistranslated, and any resulting proteins will be garbled and unable to form new viruses...

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Completely virus-proof

Carr and his colleagues have already begun eliminating redundant codons from the genome of E. coli. They are starting with the rarest, the stop codon TAG, which appears 314 times. Each instance will be replaced by a different stop codon, TAA. So far they have used MAGE to create 32 E. coli strains that each have around 10 of the necessary changes, and are now combining them to create a single strain with all the changes. Carr says this should be completed within the next few months, after which he hopes to start replacing another 12 redundant codons. To make a bacterium completely virus-proof will probably require replacing tens of thousands of redundant codons, he says, as well as modifying the protein-making factories so they no longer recognise these codons...
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FULL DETAILED ARTICLE AT : http://www.newscientist.com/article/mg21...print=true
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