Most Extensive Synthetic Genome Project to Date

World's Most “Recoded” Genome Revealed

Cambridge scientists create world’s first living organism with fully redesigned DNA

Nine years ago, researchers built a synthetic genome that was one million base pairs long. There are obvious biotechnological applications-removing the redundancies allows researchers extra codons to experiment with, potentially to develop new amino acids, proteins, and bacteria that can do new things.

It's not the first time a bacteria has been created with a synthetic DNA, but this achievement is by far the most complex achievement.

Researchers have generated E. coli with a fully synthetic genome in which three codons have been replaced with their synonyms, reports a paper published yesterday (May 15) in Nature.

In addition to shedding new light on the chemical intricacies of DNA, this type of designer bacteria can also come in handy in the medical industry.

Researchers at the University of Cambridge have rewritten the DNA of the bacteria Escherichia coli, a strain of bacteria that is normally found in soil and the human gut.

"It was completely unclear whether it was possible to make a genome this large and whether it was possible to change it so much", Jason Chin, a molecular biologist at the UK's Medical Research Council Laboratory of Molecular Biology and the scientist who led the project, tells The Guardian. 'What changes in the synthetic bacterium is that its DNA instructions are simpler while conveying the same meaning, and as a result the cellular machinery that interprets these instructions can be modified too.' Fredens explains that when particular codons are replaced, the tRNAs in charge of reading those codons and incorporating the corresponding amino acids become redundant and can be deleted as well.

The genetic code lays out the rules on how DNA is translated into a message that specifies the amino acids in a protein. The DNA letters are read in trios called codons, such as TCG and TCA.

Almost all life, from jellyfish to humans, uses 64 codons. But many of them do the same job. Each one of these three bases is also called a "codon.' The codon TCT, as per example, makes sure that an amino acid, also known as 'serine" is linked to the tail of a new protein. Chin tells Begley, "There are many possible ways you can recode a genome, but a lot of them are problematic: The cell dies". Codons containing three of the four nucleobases cytosine, guanine, adenine or thymine can encode either the start of protein synthesis, incorporating an amino acid into the protein being synthesised or terminating protein synthesis. The team also replaced every TAG codon, signaling a stop, with TAA. It's alive, but it's unlike any other life form on Earth: the scientists removed thousands of redundancies in their synthetic genome that exist in all other living creatures. Then in 2016, Church's lab replaced seven codons in parts of the E. coli genome, this time by assembling pieces of synthetic DNA.

In 2010, U.S. scientists announced the creation of the world's first organism with a synthetic genome. Commenting on the latest work, Clyde Hutchison, from the USA research group, said: "This scale of genome replacement is larger than any complete genome replacement reported so far". During the work, scientists synthesize the genome of an E. coli bacterium in their lab-all four million letters of it.

But the records may not stand for long.

"It's a landmark", said Tom Ellis, director of the Center for Synthetic Biology at Imperial College London, who was not involved in the new study.

Many companies today use genetically engineered microbes to make medicines like insulin or useful chemicals like detergent enzymes. By the time they were done, there were no natural segments in the bacteria's DNA; the whole thing was synthetic.

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