Scientists Create E. Coli With Entirely Synthetic Genome

E. coli
E. coli
Image: IDKlab (Wikimedia Commons)

Scientists created a variant of the E. coli bacteria with an entirely synthetic genome, according to a new paper.

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Building and replacing the large entire genome yet was just one goal of the team from the Medical Research Council Laboratory of Molecular Biology in Cambridge, UK. They hoped that the resulting bacteria would use a reduced number of possible DNA base pair combinations in order to produce the 20 amino acids. In the future, the now-obsolete sequences might be used to produce never-before-seen amino acids and proteins.

The thrust of the paper wasn’t just to rebuild a bacteria’s genetic code, but to simplify redundancies in order to have more genetic code to work with to create custom genomes. Genetic code is written in four letters: A, T, C, and G, which represent the molecules adenine, thymine, cytosine, and guanine. These nucleotides can arrange into 64 three-letter “codons,” most of which correspond to an amino acid, the building blocks of the proteins that allow life to function. All but two of the amino acids are encoded by multiple synonymous codons. The researchers wanted to see if they could rewrite the E. coli bacteria’s genome with fewer codons, like rewriting the dictionary but representing all hard “k” sounds with only the letter k, instead of sometimes using c or q as the English language does.

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Producing the genome required first drafting it. The researchers designed a genome where they replaced two codons that encode the amino acid serine with synonyms, and did the same with the stop codon, which tells cellular functions when to stop reading a strand of DNA while building a protein. Then, the researchers built their DNA using the various lab techniques already employed in synthetic biology. Finally, they had to replace the bacteria’s genetic material with the synthetic DNA. They couldn’t just transfer it all over—they had to break their genome into pieces, slowly transplanting bit by bit into living bacteria until they had replaced the entire E. coli genome, according to the paper published in Nature.

The E. coli survived, though they grew slower and were longer, according to New York Times reporting. But the new E. coli cells relied on only 61, rather than 64 total codons.

It was a tour de force, one scientist told Gizmodo. “For those of us who work in synthetic genomics, it’s the headline, most exciting thing; they synthesized, built, and showed that a 4-million-base-pair synthetic genome could work,” Tom Ellis, director of the Center for Synthetic Biology at Imperial College London who reviewed the paper, told Gizmodo. “It’s more than anyone had done before.”

Science-fiction speculation aside, there are several potential uses of a synthetic genome like this. 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. The codon swap is also a firewall against viruses that might try to hijack the cell, said Ellis. It’s a rapidly evolving field, and this is just one of several groups in the midst of performing these kinds of genome swaps.

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The methods that the researchers used to swap the genome provide “a blueprint for future genome synthesis,” according to the paper. And next up, the researchers hope to figure out how much more they could streamline the E. coli genome, as well as what they can do with the codons that they’ve freed up.

Science Writer, Founder of Birdmodo

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DISCUSSION

Can someone explain to me why the phrase “entirely synthetic” is applied to this genome? I understand that it was modified and streamlined in an experiment to determine the impact on the existing organism, but the codons were still composed of the same A, C, G, T amino acids that were present originally, were they not? I’m not denigrating the technical accomplishment documented here, but “synthetic” applies when you’re replacing one natural material, like cotton, with a material that doesn’t naturally occur without intervention, like polyester. So if the codons were reconstructed of, say, N, P, T, E (Nylon, Polyethylene, Teflon, Epoxy), which replaced the natural amino acids, that would be synthetic. It seems like a misapplication of the term at least, and an arrogant, misleading overstatement at worst.