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. It is believed by some that TNA could be an evolutionary pathway to RNA.
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.
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.
Pre DNA system
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. (plagiarized from https://biodesign.asu.edu/news/enzymes-allow-dna-swap-information-exotic-molecules)
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, and a precursor to RNA not because it has fewer atoms rather it is seen as more simplistic because it can be synthesised from a single starting material. TNA is able to transfer back and forth information with RNA with strands of itself that are complementary to the RNA. TNA had not been seen to demonstrate tertiary folding with functional structures that could bind ligands and catalyse reactions, and these abilities have been deemed necessary to bridge TNA and RNA. Researchers were later able to demonstrate that selected TNA molecules were able to fold into tertiary folding shapes with discrete ligand-binding properties.
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.
- Yu, Hanyang; Zhang, Su; Chaput, John C. (10 January 2012). "Darwinian evolution of an alternative genetic system provides support for TNA as an RNA progenitor". Nature Chemistry. 4 (3): 183–187. doi:10.1038/nchem.1241. Retrieved 22 April 2014.
- Science Daily, "Enzymes Allow DNA to Swap Information With Exotic Molecules", 21 March 2013
- Simpler times: Did an earlier genetic molecule predate DNA and RNA? | ASU Now: Access, Excellence, Impact
- Bradley, David (8 January 2012). "The TNA world that came before the RNA one". Chemistry World. Retrieved 22 April 2014.
- [dead link]
- 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.