Cambridge scientists create the world's first living organism with a completely redesigned DNA | Science

Scientists have created the world's first living organism with a completely synthetic and radically altered DNA code.

The laboratory-made microbe, a strain of bacteria that is normally found in the soil and in the human intestines, looks like its natural cousins ​​but survives through a smaller set of genetic instructions.

The existence of this insect proves that life can exist with a restricted genetic code and opens the way for organisms whose biological mechanisms are requisitioned to make drugs and useful material, or to add new features such as resistance to virus.

During a two-year effort, researchers at the Molecular Biology Laboratory at the University of Cambridge read and redrawed the bacteria's DNA. Escherichia coli (E. coli), before creating cells with a synthetic version of the modified genome.

The artificial genome contains 4 m of base pairs, the units of the genetic code spelled G, A, T and C. Printed entirely on A4 sheets, it is 970 pages long, making it the genome by far the most important scientists. never built.

"It was completely unclear whether it was possible to create a genome of this size and modify it as much," said Jason Chin, an expert in synthetic biology who led the project.

The DNA wrapped in a cell contains the instructions necessary for its operation. When the cell needs more proteins to grow, for example, it reads the DNA that codes for the correct protein. The DNA letters are read in trios called codons, such as TCG and TCA.

Almost all of life, jellyfish to humans, uses 64 codons. But many of them do the same job. In total, 61 codons make up 20 natural amino acids, which can be linked to each other like beads on a chain to construct any natural protein. Three other codons are actually signs of arrest: they inform the cell of when the protein is complete, as the complete stop marking the end of that sentence.

The Cambridge team undertook to rethink the E coli genome by removing some of its superfluous codons. Working on a computer, the scientists analyzed the insect's DNA. Whenever they encountered the TCG, a codon that makes an amino acid called serine, they re-wrote it under the name AGC, which did the same job. They replaced two other codons in the same way.

More than 18,000 changes later, scientists had removed each occurrence of the three codons of the insect's genome. The remodeled genetic code was then synthesized chemically and, piece by piece, added to E coli where he replaced the natural genome of the body. The result, reported in Nature, is a microbe with a completely synthetic and radically modified DNA code. Known as Syn61, the bug is a little longer than normal and grows more slowly, but still survives.

"It's really amazing," Chin said. When the virus was created, shortly before Christmas, the research team took a picture taken in the laboratory with a plate of microbes as the central figure of a reproduction of the nativity.

In Chin's opinion, such life forms of designers could be useful. Because their DNA is different, invading viruses will have trouble spreading inside them, making them more resistant. This 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 diseases, but cycles Complete production processes can be wasted when bacterial cultures are contaminated with viruses or other microbes. But that is not all: in future work, the released genetic code could be reused to allow cells to produce enzymes, proteins and synthetic drugs.

In 2010, US scientists announced the creation of the first body in the world with a synthetic genome. L & # 39; insect Mycoplasma Mycoides, has a genome smaller than E coli – about 1 m base pair – and has not been radically redesigned. Commenting on the latest work, Clyde Hutchison, of the US research group, said, "This genome replacement scale is superior to that of any complete genome replacement reported so far."

"They have propelled the field of synthetic genomics to a higher level, not only by successfully building the largest synthetic genome to date, but also by making the most coding modifications possible to a genome," said Tom Ellis, researcher in synthetic biology at Imperial. College London.

But the records may not last long. Ellis and others are building a synthetic genome for baker's yeast, while Harvard scientists are creating bacterial genomes with more coding changes. That the redesigned E coli does not grow as well as natural strains is not surprising, added Ellis. "If anything is amazing, it grows at all after so many changes," he said.