Experimental Evidence That GNA and TNA Were Not Sequential Polymers in the Prebiotic Evolution of RNA

Systematic investigation into the chemical etiology of ribose has led to the discovery of glycerol nucleic acid (GNA) and threose nucleic acid (TNA) as possible progenitor candidates of RNA in the origins of life. Coupled with their chemical simplicity, polymers for both systems are capable of forming stable Watson-Crick antiparallel duplex structures with themselves and RNA, thereby providing a mechanism for the transfer of genetic information between successive genetic systems. Investigation into whether both polymers arose independently or descended from a common evolutionary pathway would provide additional constraints on models that describe the emergence of a hypothetical RNA world. Here we show by thermal denaturation that complementary GNA and TNA mixed sequence polymers are unable, even after prolonged incubation times, to adopt stable helical structures by intersystem cross-pairing. This experimental observation suggests that GNA and TNA, whose structures derive from one another, were not consecutive polymers in the same evolutionary pathway to RNA.

[1]  Eric Meggers,et al.  A simple glycol nucleic acid. , 2005, Journal of the American Chemical Society.

[2]  J. Szostak,et al.  Kinetic Analysis of an Efficient DNA-Dependent TNA Polymerase , 2005, Journal of the American Chemical Society.

[3]  Warren Belisle,et al.  Carbonaceous meteorites as a source of sugar-related organic compounds for the early Earth , 2001, Nature.

[4]  K. Breslauer,et al.  Calculating thermodynamic data for transitions of any molecularity from equilibrium melting curves , 1987, Biopolymers.

[5]  T. Steitz,et al.  The complete atomic structure of the large ribosomal subunit at 2.4 A resolution. , 2000, Science.

[6]  C. Vonrhein,et al.  Structure of the 30S ribosomal subunit , 2000, Nature.

[7]  A. Holý Aliphatic analogues of nucleosides, nucleotides, and oligonucleotides , 1975 .

[8]  A. Eschenmoser,et al.  Chemical etiology of nucleic acid structure , 2000 .

[9]  J. Szostak,et al.  An in Vitro Selection System for TNA , 2005, Journal of the American Chemical Society.

[10]  A W Schwartz,et al.  The case for an ancestral genetic system involving simple analogues of the nucleotides. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[11]  V. Ramakrishnan,et al.  Structure of the 30 S ribosomal subunit , 2022 .

[12]  P. Scholz,et al.  The α‐L‐Threofuranosyl‐(3′→2′)‐oligonucleotide System (‘TNA'): Synthesis and Pairing Properties , 2002 .

[13]  G. F. Joyce RNA evolution and the origins of life , 1989, Nature.

[14]  S. Pitsch,et al.  Pyranosyl-RNA ("p-RNA"). NMR and molecular-dynamics study of the duplex formed by self-pairing of ribopyranosyl-(C-G-A-A-T-T-C-G) , 1996 .

[15]  W. Gilbert Origin of life: The RNA world , 1986, Nature.

[16]  B. Ganem RNA world , 1987, Nature.

[17]  R. S. Andrews,et al.  Synthesis of propane-2,3-diol combinatorial monomers , 1996 .

[18]  J. Chaput,et al.  Nonenzymatic Oligomerization on Templates Containing Phosphodiester-Linked Acyclic Glycerol Nucleic Acid Analogues , 2000, Journal of Molecular Evolution.

[19]  G. F. Joyce The antiquity of RNA-based evolution , 2002, Nature.

[20]  S. Benner,et al.  Oligonucleotides containing flexible nucleoside analogs , 1990 .

[21]  T. Earnest,et al.  Crystal Structure of the Ribosome at 5.5 Å Resolution , 2001, Science.

[22]  J. Szostak,et al.  Glycerol nucleoside triphosphates: synthesis and polymerase substrate activities. , 2006, Organic letters.

[23]  Martin Egli,et al.  Crystal structure of a B-form DNA duplex containing (L)-alpha-threofuranosyl (3'-->2') nucleosides: a four-carbon sugar is easily accommodated into the backbone of DNA. , 2002, Journal of the American Chemical Society.

[24]  T. Cech,et al.  Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena , 1982, Cell.