THE genetic alphabet just got 50 per cent bigger. A bacterium has been engineered not only to have two more 鈥渓etters鈥� in its DNA, but to use them to make new proteins that have never existed in nature.
The genes carried on DNA are instruction manuals for making proteins, which do essential jobs like digesting food and fighting infection. The letters that make up the genetic code are molecules called bases. All known living things use the same four letters: A, C, G and T.
The new bacterium has two more synthetically engineered bases, called 鈥淴鈥� and 鈥淵鈥�.
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at the Scripps Research Institute in La Jolla, California, and his team have been working on X and Y for 13 years. In 2014, they moved them from a test tube into an E. coli bacterium. The cell was able to copy the DNA with X and Y in it, and pass that DNA to its daughter cells.
Now they have gone a step further and used the altered DNA to make new proteins (Nature, ).
鈥淓very protein ever translated has been decoded using a four-letter alphabet, but now we鈥檝e decoded proteins using a six-letter one,鈥� says Romesberg.
Cells make proteins by stringing together smaller molecules called amino acids. They do this in factories called ribosomes, which use the letters from the DNA as instructions.
鈥淓very protein ever made was built using a four-letter alphabet. We鈥檙e using a six-letter one鈥�
The letters are read in groups of three, such as 鈥淎CG鈥�, called codons. There are 64 possible codons, which is more than enough to specify the 20 amino acids used in nature. But Romesberg鈥檚 bacterium is far more versatile. Thanks to the extra two letters, the number of possible three-letter codons jumps to 216.
The 152 new codons can be assigned to amino acids beyond the original 20. New amino acids mean new proteins, which might be able to do different things from their counterparts found in nature.
鈥淲ork such as this shows that the genetic code鈥� is malleable and subject to expansion,鈥� says at Yale University in Connecticut.
It is a 鈥渓andmark development鈥�, says at the University of Pittsburgh in Pennsylvania. It is doubly significant because the new bases are linked by a different type of chemical bond not previously used in DNA.
In the short term, Romesberg says it could lead to new protein-based drugs, improving therapies used to treat cancers and autoimmune disorders. But in the longer term, he wants to make new types of life that can do things that natural organisms can鈥檛. He suggests creating microorganisms that can target specific cells or organs in our bodies for therapies, or clean up oil spills by breaking down pollutants into safer chemicals.
鈥淲hat proteins can do must somehow be limited by the building blocks they can use,鈥� says Romesberg. 鈥淚f we give them new building blocks, there must be something new they can do.鈥�
Romesberg says the study is also evidence that life could have evolved in many ways, and that life on another planet could be genetically different to anything on Earth. 鈥淚t鈥檚 been a question for hundreds of years: are we the way we are because we鈥檙e the only solution, or a solution?鈥� he says. 鈥淚n the smallest possible way, but for the first time, we have data that suggests we are merely a solution.鈥�
Romesberg鈥檚 study is the latest to expand the existing genetic code. Last year, another team reported they were part way through recoding an E. coli bacterium with an alternate genetic code, so that it could make proteins with up to four artificial amino acids.
This article appeared in print under the headline 鈥淭wo new letters added to the genetic alphabet鈥�
