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BIOCHEMISTRY
"TNA is a pretty interesting molecule that was discovered by Albert Eschenmoser [see page 48] in a search for possible progenitors of RNA or DNA, the kinds of molecules that might have been the early genetic molecules in the origin of life," says team leader Jack W. Szostak, a Howard Hughes Medical Institute investigator and professor of genetics in the molecular biology department at Harvard Medical School. "We're very interested in learning anything we can about the capabilities of TNA. Basically the question is, 'Could there have been a TNA world before the RNA world?' " Szostak, postdoc John C. Chaput, and graduate student Justin K. Ichida used an assay to find DNA polymerases that would work with a TNA template that consisted of a primer, a six-base DNA "running start," and a nine-base TNA region. Most of the polymerases were able to catalyze the synthesis of DNA one to three nucleotides into the TNA region of the template, and some of the polymerases showed traces of the full-length DNA product [J. Am. Chem. Soc., 125, 856, (2003)]. "There's quite a bit of variation between polymerases," Szostak says. "Some really don't like to work on TNA at all. Others were surprisingly good." The results encourage Szostak to believe that evolving a suitable polymerase will be easier than he had originally thought. So far, Szostak has demonstrated half of what's needed to replicate TNA. In other work, his group is looking for enzymes that can make TNA from a DNA template. "It would be nice if we had a single enzyme that could do both reactions," Szostak says. "That requires modifying an existing DNA polymerase in two ways: It has to recognize the TNA template, and it also has to be able to synthesize TNA. We've decided to simplify things by breaking it down into the two separate steps." Leslie E. Orgel, a professor at the Salk Institute for Biological Studies in La Jolla, Calif., says that the work "may be the first step in the development of an artificial replicating system that, though still dependent on protein enzymes, is capable of evolving under selection." In addition, "in the context of the origin of life," Szostak's work also "supports the idea that a simpler genetic polymer could be taken over by a more complicated polymer," Orgel says. |
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