This advantage in structural simplicity was originally thought to be an Achilles' heel for TNA, making its binding behavior incompatible with DNA and RNA. Surprisingly, however, research has now shown that a single strand of TNA can indeed bind with both DNA and RNA by Watson-Crick base pairinga fact of critical importance if TNA truly existed as a transitional molecule capable of sharing information with more familiar nucleic acids that would eventually come to dominate life.
In the current study, Chaput and his group use an approach known as molecular evolution to explore TNA's potential as a genetic biomolecule. Such work draws on the startling realization that fundamental Darwinian propertiesself-replication, mutation and selectioncan operate on non-living chemicals.
Extending this technique to TNA requires polymerase enzymes that are capable of translating a library of random DNA sequences into TNA. Once such a pool of TNA strands has been generated, a process of selection must successfully identify members that can perform a given function, excluding the rest. As a test case, the team hoped to produce through molecular evolution, a TNA strand capable of acting as a high-specificity, high-affinity binding receptor for the human protein thrombin.
They first attempted to demonstrate that TNA nucleotides could attach by complementary base pairing to a random sequence of DNA, forming a hybrid DNA-TNA strand. A DNA polymerase enzyme assisted the process. Many of the random sequences, however, contained repeated sections of the guanine nucleotide, which had the effect of pausing the transcription of DNA into TNA. Once random DNA libraries were built excluding guanine, a high yield of DNA-TNA hybrid strands was produced.
|Contact: Joseph Caspermeyer|
Arizona State University