Threose nucleic acid
Threose nucleic acid (TNA) is an artificial genetic polymer invented by Albert Eschenmoser. TNA has a backbone structure composed of repeating threose sugars linked together by phosphodiester bonds. Like DNA and RNA, TNA can store genetic information in strings of nucleotide sequences (G, A, C, and T). TNA is not known to occur naturally and is synthesized chemically in the laboratory under controlled conditions.
TNA can self-assemble by Watson-Crick base pairing into duplex structures that closely approximate the helical geometry of A-form RNA. TNA can also form base pairs complementary to strands of DNA and RNA, which makes it possible to share information with natural genetic polymers. This capability and chemical simplicity suggests that TNA could have preceded RNA as a genetic material.
Polymerases have been identified that can replicate TNA polymers in the laboratory. TNA replication occurs through a process that mimics RNA replication. In these systems, TNA is reverse transcribed into DNA, the DNA is amplified by the polymerase chain reaction and then forward transcribed back into TNA.
TNA replication coupled with in vitro selection has produced a TNA aptamer that binds to human thrombin. This example demonstrates that TNA is capable of heredity and evolution, which is a hallmark of life. TNA can fold into complex shapes which can bind to a desired target with high affinity and specificity. It may be possible to evolve TNA enzymes with functions required to sustain early life forms.
TNA has generated great interest in synthetic biology because TNA polymers are resistant to nuclease degradation. This property, coupled with its ability to undergo Darwinian evolution in a test-tube, provide a possible path to biologically stable molecules with relevance in material science and molecular medicine.
Pre DNA system
John Chaput, a researcher at the Center for Evolutionary Medicine, has theorized that issues concerning the prebiotic synthesis of ribose sugars and the non-enzymatic replication of RNA may provide circumstantial evidence of an earlier genetic system more readily produced under primitive earth conditions. TNA could have been an early genetic system. The research paves the way for more sophisticated manipulation of TNA and other xenonucleic acids and may strengthen the case that TNA or a closely related molecule set the stage for the emergence of RNA and the first earthly life.
Recent advances in protein engineering have produced a new breed of synthetic polymerases. In the current study, one of these – known as Therminator DNA polymerase, faithfully transcribed a 70 nucleotide DNA sequence into TNA, while another, known as SuperScript II (SSII) performed reverse-transcription back into DNA with impressively high fidelity. Sequences of both 3-letter and 4-letter DNA messages were transcribed and reverse transcribed, both with over 90 percent accuracy.
TNA commercial applications
Research data in the Journal of the American Chemical Society, demonstrated 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.
- Orgel, Leslie (November 2000). "A Simpler Nucleic Acid". Science 290 (5495): 1306–1307. doi:10.1126/science.290.5495.1306. PMID 11185405.
- Watt, Gregory (February 2005). "Modified nucleic acids on display". Nature Chemical Biology. doi:10.1038/nchembio005.
- Schoning, K; Scholz P; Guntha S; Wu X; Krishnamurthy R; Eschenmoser A (November 2000). "Chemical etiology of nucleic acid structure: the alpha-threofuranosyl-(3'->2') oligonucleotide system.". Science 290 (5495): 1347–51. doi:10.1126/science.290.5495.1347. PMID 11082060.
- Was simple TNA the first nucleic acid on Earth to carry a genetic code?, New Scientist (behind paywall)
- ORIGIN OF LIFE: A Simpler Nucleic Acid, Leslie Orgel