In a milestone for synthetic biology, colonies of E. coli thrive with DNA constructed from scratch by humans, not nature.
A major step forward in the field of synthetic biology, it marks the first time that a living organism has ever been created with a genetic code that is completely manufactured by humans, not nature.
In a paper published in the journal Nature, researchers from the Medical Research Council Laboratory of Molecular Biology in Britain revealed that they were able to make an E. coli in the laboratory made up completely of synthetic genes.
The lab-made microbe, a strain of bacteria that is normally found in soil and the human gut, is similar to its natural cousins but survives on a smaller set of genetic instructions.
Genes, Codons That Make Up The Genome
An organism's genome is made up of genes, each one of which is comprised of four nucleotide bases: adenine (A), thymine (T), guanine (G), and cytosine (C).
The DNA coiled up inside a cell holds the instructions it needs to function. When the cell needs more protein to grow, for example, it reads the DNA that encodes the right protein. The DNA letters are read in trios called codons, such as TCG and TCA.
In most living organisms, these nucleotide bases are strung together in 64 groups of three known as "codons". Each three-letter combination corresponds to one of the 20 amino acids, which in turn are strung together to form proteins. Sixty-one codons produce the 20 amino acids, while the last three are stop codons that signal the end of production.
Study lead author Jason Chin, a molecular biologist at the MRC laboratory, explained to New York Times that he and his team were curious about all the redundancies in the genetic code. The researchers asked if all 64 codons are necessary to create life.
“It was completely unclear whether it was possible to make a genome this large and whether it was possible to change it so much,” study co-author Jason Chin, a biologist at the University of Cambridge.
The new synthetic organism, Escherichia coli Syn61, on plates. Photograph: Handout
Creating A New, More Streamlined Version Of E. Coli
To answer the question, Chin and his team set out to develop a new version of E. coli that only uses 61 codons to make all the amino acids that the organism needs.
The product of a two-year research campaign, the redesigned DNA consists of four million segments—four times more than the previous record holder.
The researchers basically streamlined the DNA sequence by making serine with four codons instead of six and using two stop codons instead of three. With this technique, they completely redesigned the E. coli's genetic code, calling it Syn61.
The next challenge is actually making the bacteria. Since the genome was too complex to transfer into an E. coli in one go, the researchers had to build the genome in small segments and replace the original genome piece by piece until no natural segments were left. Amazingly, the E. coli survived, albeit elongated cells and slower to reproduce.
Despite this seeming disparity, the synthetic bacteria appear to function much like normal E. coli. The main differences, as The New York Times’ Carl Zimmer reports, are a slower growth rate and longer length.
"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, who reviewed the paper and is the director of the Center for Synthetic Biology at Imperial College London, told Gizmodo. "It's more than anyone had done before."
What is DNA and How Does it Work? Credit: Stated Clearly
In the future, Chin and his colleagues hope to streamline the E. coli genome even further, removing more redundancies and simplifying the genetic code. Not only are they curious to find out how simple the genome could be while still supporting life, but it would leave researchers space to experiment with the extra codons and create new amino acids, proteins, and cells.
Such designer lifeforms could come in handy, Chin believes. Because their DNA is different, invading viruses will struggle to spread inside them, making them in effect virus-resistant. That could bring benefits. E coli is already used by the biopharmaceutical industry to make insulin for diabetes and other medical compounds for cancer, multiple sclerosis, heart attacks and eye disease, but entire production runs can be spoiled when bacterial cultures are contaminated with viruses or other microbes.
But that's not all: Another key implication of the study centers on amino acids. As BBC News’ Roland Pease writes, the E. coli genome’s use of 61 out of 64 possible codons leaves three open for reprogramming, opening the doorway for “unnatural building blocks” capable of performing previously impossible functions.