Scientists Add New Letters To DNA's 'Alphabet'

Chemical biologist Floyd Romesberg and his colleagues have succeeded in creating two artificial DNA 'letters' that are accurately replicated by a natural enzyme. These two new base pairs could radically rewrite the rules of genetic engineering.

Life on Earth evolved with genetic code that is made from different arrangements of four genetic "bases," The bases are divided into two pairs, which bond on opposite strands of a DNA molecule. This forms the rungs of the double-helix ladder of DNA.

Romesberg set up experiments that generated thousands of potential bases at random, and then screened them to see of any would be treated normally by a polymerase enzyme. h the help of graduate student Aaron Leconte, the group synthesized and screened 3600 candidates. Two different screening approaches turned up the same pair of molecules, called dSICS and dMMO2.

"We now have an unnatural base pair that's efficiently replicated and doesn't need an unnatural polymerase," says Romesberg. "It's staring to behave like a real base pair... "We still don't have a detailed understanding of how replication happens," added Romesberg. "Now that we have an unnatural base pair, we are continuing experiments to understand it better."

Science fiction fans are less shocked by this development, having already seen this particular future in the X-files. The following dialog is from The Erlenmeyer Flask, first aired in 1994.

CARPENTER: These are the DNA sequences from the bacteria sample you brought in. You seem to know something about molecular biology. Do you know what you're looking at?

SCULLY: Yeah, I think those are genes.

CARPENTER: Right. They're called base pairs. Each pair is made up of something called a nucleotide. Only four nucleotides exist in DNA. Four. And through some miracle of design that we have yet to fathom, every living thing is created out of these four basic building blocks. What you're looking at is a sequence of genes from the bacteria sample. Normally, we'd find no gaps in the sequence. But with these bacteria, we do.

SCULLY: Why is that?

CARPENTER: I don't know why. But I tell you, under any other circumstances, my first call would have been to the government.

SCULLY: What exactly did you find?

CARPENTER: A fifth and sixth DNA nucleotide. A new base pair. Agent Scully, what are you looking at... it exists nowhere in nature. IT would have to be, by definition... extraterrestrial.

Romesberg's ultimate goal? "We want to import these into a cell, study RNA trafficking, and in the longest term, expand the genetic code and 'evolvability' of an organism."

Via New Scientist; thanks to Eric Nodacker for the tip and sf reference.

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