Enzymes allow DNA to swap information with exotic molecules

Mar. 21, 2013 The discovery of the Rosetta Stone resolved a longstanding puzzle, permitting the translation of Egyptian hieroglyphs into Ancient Greek.

John Chaput, a researcher at Arizona State University's Biodesign Institute has been hunting for a biological Rosetta Stone -- an enzyme allowing DNA's 4-letter language to be written into a simpler (and potentially more ancient) molecule that may have existed as a genetic pathway to DNA and RNA in the prebiotic world.

Research results, which recently appeared in the Journal of the American Chemical Society, demonstrate that DNA sequences can be transcribed into a molecule known as TNA and reverse transcribed back into DNA, with the aid of commercially available enzymes.

The significance of the research is three-fold:

In the case of biomedical applications, XNAs may be developed into aptamers -- molecular structures that can mimic the properties of naturally occurring polymers, folding into a variety of 3-dimensional forms and binding with selected targets. Aptamers are useful for a range of clinical applications including the development of macromolecular drugs.

"TNA is resistant to nuclease degradation, making it an ideal molecule for many therapeutic and diagnostic applications," Chaput says.

The structural plans for organisms ranging from bacteria to primates (including humans) are encrypted in DNA using an alphabetic code consisting of just A, C, T & G, which represent the 4 nucleic acids. In addition to their information-carrying role, DNA and RNA possess two defining properties: heredity, (which allows them to propagate their genetic sequences to subsequent generations) and evolution, (which allows successive sequences to be modified over time and to respond to selective pressure).

The chemical complexity of DNA has convinced most biologists that it almost certainly did not arise spontaneously from the prebiotic soup existing early in earth's history. According to one hypothesis, the simpler RNA molecule may at one time have held dominion as the sole transmitter of the genetic code. RNA is also capable of acting as an enzyme and may have catalyzed important chemical reactions leading eventually to the first cellular life.

But RNA is still a complex molecule and the search for a simpler precursor that may have acted as a stepping-stone to the RNA, DNA and protein system that exists today has been intense.

A variety of xenonucleic acids are being explored as candidates for the role of transitional molecule. In the current study, threose nucleic acid or TNA is investigated. Chaput says that establishing TNA as a progenitor of RNA would require demonstrating that TNA can perform functions that would help support a pre-RNA world. Of particular importance, would have been the ability replicate itself in the absence of protein enzymes.

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Enzymes allow DNA to swap information with exotic molecules