Scientists add new letters to bacteria's genetic 'alphabet'

For possibly billions of years, the DNA blueprints for life on Earth have been written with just four genetic "letters" -- A, T, G and C. On Wednesday, scientists announced that that they added two more.

In a paper published in the journal Nature, bio-engineers at Scripps Research Institute in La Jolla said they had successfully inserted two synthetic molecules into the genome of an Escherichia coli bacterium, which survived and passed on the new genetic material.

In addition to the naturally occurring nucleotides adenine, thymine, guanine and cytosine, which form the rungs of DNA's double-helix structure, the bacterium carried two more base-pair partners, which study authors have dubbed d5SICS and dNaM.

For more than a decade, scientists have been experimenting with so-called unnatural base pairs, or UBPs, saying they may hold the key to new antibiotics, future cancer drugs, improved vaccines, nanomaterials and other innovations.

Until now, however, those experiments have all been conducted in test tubes.

"These unnatural base pairs have worked beautifully in vitro, but the big challenge has been to get them working in the much more complex environment of a living cell," lead study author Denis Malyshev, a molecular and chemical biologist at Scripps, said in a prepared statement.

The new genetic material did not appear to be toxic to the bacteria, and it only remains in the organism's genome under specific lab conditions. In a natural environment, the molecules -- nucleoside triphosphates -- degrade and disappear in a day or two. Once they disappear, the bacterium reverts back to its natural base pair arrangement.

Still, experts said insertion of the synthetic materials into E. coli's genome was a milestone.

"This definitely is a significant achievement," said Ross Thyer, a synthetic biologist at the University of Texas at Austin, who was not involved in the research. "What I'm most excited about is how this will help us answer some bigger evolutionary questions: Why has life settled on a specific set of bases."

Malyshev and colleagues went about creating the semi-synthetic bacterium by genetically engineering a stretch of ring-like DNA known as a plasmid.

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Scientists add new letters to bacteria's genetic 'alphabet'