Synthesis of information-carrying polymers of mixed sequences from double stranded short deoxynucleotides
Tóm tắt
The "RNA World" hypothesis suggests that an early form of life on Earth was based on nucleic acid strands able to store genetic information and catalyze a wide range of reactions including those which lead to self-replication. For this hypothesis to be true there must exist an efficient process for creating RNA or RNA-like polymers of mixed sequences from short precursors, where these polymers have to be long enough to fold into catalytically active structures (at least 40 bases). We report on the polymerization of dimeric to hexameric 5'-amino- oligodeoxynucleotides 3'-phosphates in the presence of the water-soluble carbodiimide EDC. Non-complementary single stranded nucleotides fail to polymerize and yield di- to hexameric cyclooligomers or capped EDC-adducts unable to undergo further 3'-5'-phosphoramidate formation. Complementary building blocks polymerize with a conversion close to 100% when starting from a concentration of typically 20 mM. The reactions proceed within a few hours yielding strands of mixed pyrimidine-purine sequences up to 300 bases long. The maximum length of the products depends on the type of the starting oligonucleotides. Copolymerization of a dimer alphabet consisting of equimolar quantities of all four sequences d(nYRp), where Y are pyrimidines and R are purines, generates a mixed-sequence library of 50-70 mers. Libraries of long oligonucleotides with potentially catalytic activity are formed from short precursors within hours. Reactions occur via blunt end ligation of the double strands, and the reaction rates correlate with stacking interactions at the ligation sites. Circular dichroism measurements, polarized light microscopy and fluorescence microscopy suggest the formation of supramolecular aggregates during chain growth. These aggregates accelerate the reactions by increasing the local concentration of the reactants in a non-sequence-specific templating mode. Aggregation of the double strands into higher order "compartimented" structures might have been the key for the formation of the first inhabitants of the "RNA World".
Tài liệu tham khảo
Gilbert W: The RNA World. Nature 1986, 319: 618. 10.1038/319618a0
Powner MW, Gerland B, Sutherland JD: Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 2009, 45: 239–242. 10.1038/nature08013
Fuller WD, Sanchez RA, Orgel LE: Studies in prebiotic synthesis VI. Synthesis of purine nucleosides. J Mol Biol 1972, 67: 25–33. 10.1016/0022-2836(72)90383-X
Lincoln TA, Joyce GF: Self- sustained replication of an RNA enzyme. Science 2009, 323: 1229–1232. 10.1126/science.1167856
Sievers D, von Kiedrowski G: Self-replication of complementary nucleotide-based oligomers. Nature 1994, 369: 221–224. 10.1038/369221a0
Ekland EH, Szostak JW, Bartel DP: Structurally complex and highly active RNA ligases derived from random RNA sequences. Science 1995, 269: 364–370. 10.1126/science.7618102
Takeuchi N, Hogeweg P: Evolution of complexity in RNA-like replicator systems. Biology Direct 2008, 3: 11. 10.1186/1745-6150-3-11
Turk RM, Chumachenko NV, Yarus M: Multiple translational products from a five-nucleotide ribozyme. Proc Natl Acad Sci USA 2010, 107: 4585–4589. 10.1073/pnas.0912895107
Kauffman SA: Autocatalytic Sets of Proteins. J Theor Biol 1986, 119: 1–24. 10.1016/S0022-5193(86)80047-9
Lee DH, Granja JR, Martinez JA, Severin K, Ghadiri MR: A self-replicating peptide. Nature 1996, 382: 525–528. 10.1038/382525a0
Vidonne A, Philp D: Making molecules make themselves - the chemistry of Artificial Replicators. Eur J Org Chem 2009, 5: 593–610. 10.1002/ejoc.200800827
Orgel LE, Lohrmann R: Prebiotic chemistry and nucleic acid replication. Acc Chem Res 1974, 7: 368–377. 10.1021/ar50083a002
Sleeper HR, Lohrmann R, Orgel LE: Formation of the Imidazolides of dinucleotides under potentially prebiotic conditions. J Mol Evol 1978, 11: 87–93. 10.1007/BF01733884
Constanzo G, Pino S, Ciciriello F, Di Mauro E: Generation of Long RNA Chains in Water. J Biol Chem 2009, 284: 33206–33216. 10.1074/jbc.M109.041905
Rajamani S, Vlassov A, Benner S, Coombs A, Olasagasti F, Deamer D: Lipid-assisted synthesis of RNA-like polymers from mononucleotides. Orig Life Evol Biosph 2008, 38: 57–74. 10.1007/s11084-007-9113-2
Ferris JP, Hill AR Jr, Liu R, Orgel LE: Synthesis of long prebiotic oligomers on mineral surfaces. Nature 1996, 381: 59–61. 10.1038/381059a0
Monnard PA, Kanavarioti A, Deamer DW: Eutectic phase polymerization of activated ribonucleotide mixtures yields quasiequimolar incorporation of purine and pyrimidine nucleobases. J Am Chem Soc 2003, 125: 13734–13740. 10.1021/ja036465h
Zielinski WS: Oligoaminonucleoside phosphoramidates. Oligomerization of dimers of 3'-amino-3'-deoxynucleotides (GC and CG) in aqueous solution. Nucl Acids Res 1987, 15: 1699–1715. 10.1093/nar/15.4.1699
Bolli M, Micura R, Eschenmoser A: Pyranosyl-RNA: chiroselective self-assembly of base sequences by ligative oligomerization of tetranucleotide-2',3'-cyclophosphates (with a commentary concerning the origin of biomolecular homochirality). Chemistry & Biology 1997, 4: 309–320.
Horrowitz ED, Engelhart AE, Chen MC, Quarles KA, Smith MW, Lynn DG, Hud NV: Intercalation as a means to suppress cyclization and promote polymerization of base-pairing oligonucleotides in a prebiotic world. Proc Natl Acad Sci 2010, 107: 5288–5293. 10.1073/pnas.0914172107
Nakata M, Zanchetta G, Chapman BD, Jones CD, Cross JO, Pindak R, Bellini T, Clark NA: End-to-end stacking and liquid crystal condensation of 6-to 20-base pair DNA duplexes. Science 2007, 318: 1276–1279. 10.1126/science.1143826
Zielinski WS, Orgel LE: Autocatalytic synthesis of a tetranucleotide analogue. Nature 1987, 327: 346–347. 10.1038/327346a0
Lohrmann R, Orgel LE: Self-Condensation of activated dinucleotides on polynucleotide templates with alternating sequences. J Mol Evol 1979, 14: 243–250. 10.1007/BF01732491
Gotoh O, Tagashira Y: Stabilities of nearest-neighbor doublets in double-helical DNA determined by fitting calculated melting profiles to observed profiles. Biopolymers 1981, 20: 1033–1042. 10.1002/bip.1981.360200513
Röthlingshöfer M, Richert C: Chemical primer extension at submillimolar concentration of deoxynucleotides. J Org Chem 2010, 75: 3945–3952. 10.1021/jo1002467
Rajamani S, Ichida JK, Antal T, Treco DA, Leu K, Nowak MA, Szostak JW, Chen IA: Effect of stalling after Mismatches on the error catastrophe in nonenzymatic nucleic acid replication. J Am Chem Soc 2010, 132: 5880–5885. 10.1021/ja100780p
Shabarova ZA, Dolinnaya NG, Drutsa VL, Melinkova NP, Purmal AA: DNA-like duplexes with repetitions. III. Efficient template-guided chemical polymerization of d(TGGCCAAGCTp). Nucl Acids Res 1981, 9: 5747–5761. 10.1093/nar/9.21.5747
Von Kiedrowski G, Wlotzka B, Helbing J: Sequence dependence of template-directed synthesis of hexadenoxynucleotide derivates with 3'-5' pyrophosphate linkage. Angew Chem Int Ed Engl 1989, 28: 1235–1237. 10.1002/anie.198912351
Yakovchuk P, Protozanova E, Frank-Kamenetskii MD: Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucl Acids Res 2006, 34: 564–574. 10.1093/nar/gkj454
Ghirlando R, Wachtel EJ, Arad T, Minsky A: DNA packaging induced by micellar aggregates: a novel in vitro DNA condensation system. Biochemistry 1992, 31: 7110–7119. 10.1021/bi00146a012
Kornyshev AA, Wynveen A: The homology recognition well as an innate property of DNA structure. Proc Natl Acad Sci 2009, 106: 4683–4688. 10.1073/pnas.0811208106
Baldwin GS, Brooks NJ, Robson RE, Wynveen A, Goldar A, Leikin A, Seddon JM, Kornyshev AA: DNA double helices recognize mutual sequence homology in a protein free environment. J Phys Chem B 2008, 112: 1060–10648. 10.1021/jp7112297
Barsky D, Colvin ME, Zon G, Gryaznov SM: Hydration effects on the duplex stability of phosphoramidate DNA-RNA oligomers. Nucl Acids Res 1997, 25: 830–835. 10.1093/nar/25.4.830