Published: Fri, January 27, 2017
Research | By Jennifer Evans

Scientists add two extra letters to life's genetic code

Scientists add two extra letters to life's genetic code

Every living being on Earth is made up of a DNA code that contains four bases, which are represented by the letters G, T, C and A. These bases "pair up" to form two base pairs - to become what scientists call "the rungs of the DNA ladder".

Modifying existing organisms with synthetic DNA could allow the repurposing of organisms for a variety of useful functions, such as designing new proteins for use in drug discovery, producing biomaterials or as novel treatments for disease.

"Your genome isn't just stable for a day", Romesberg said on the breakthrough.

The researchers discovered a modification to the transporter that that made it much easier for the organism to grow and divide while holding on to X and Y. They then optimised their previous version of Y, creating a chemically different molecule that can be better recognised by the enzymes that synthesise DNA molecules during DNA replication.

Now researchers from The Scripps Research Institute (TSRI) in the USA are forging a whole new path for what the definition of life is, after forging the first new semisynthetic organisms with an expanded DNA code. "This SSO is thus a form of life that can stably store genetic information using a six-letter, three-base-pair alphabet".

They were able to take advantage of the tool to ensure that any cells that dropped X and Y would be marked for destruction by the organism.

Gene editing tool CRISPR-Cas9 was then used as a means of building genetic self-protection measures into the E. coli.

"The transporter was used in the 2014 study, but it made the semisynthetic organism very sick", explains one of the team, Yorke Zhang.

The plasmid DNA contained natural A-T and C-G base pairs together with a d5SICS-dNaM base pair. The new organism considers any genetic sequence without the X and Y as threats while those with the X and Y blocks survive.

"We were able to address the problem at a fundamental level", said Lamb, who now serves as a research scientist at Vertex Pharmaceuticals.

Initially, the engineered bacteria were weak and sickly, and would die soon after they received their new base pair, because they couldn't hold onto it as they divided.

"E$3 volution works by starting with something close, and then changing what it can do in small steps", Romesberg told Ian Sample at The Guardian.

Romesberg said: "We can now get the light of life to stay on". "That suggests that all of life's processes can be subject to manipulation".

He also said the actual applications for the synthetic base pair are zero right now - organisms can't currently read or process the base pair into something of value.

Additional authors of the study, "A semisynthetic organism engineered for the stable expansion of the genetic alphabet", were Aaron W. Feldman and Anne Xiaozhou Zhou of TSRI; Thomas Lavergne of the University of Grenoble; and Lingjun Li of Henan Normal University.

The next step will be to demonstrate that unnatural DNA within bacteria can be transcribed into the RNA molecules that feed genetic instructions to protein-making machinery in cells.

'That was a big breakthrough for us - an enabling breakthrough, ' said co-author Dr Denis Malyshev, also from the Scripps Research Institute.

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