RSS-Feed abonnieren
DOI: 10.1055/s-0036-1588646
Our Odyssey to Find a Plausible Prebiotic Path to RNA: The First Twenty Years
Publikationsverlauf
Received: 05. September 2016
Accepted after revision: 13. Oktober 2016
Publikationsdatum:
05. Dezember 2016 (online)
![](https://www.thieme-connect.de/media/synlett/201701/lookinside/thumbnails/st-2016-s0588-a_10-1055_s-0036-1588646-1.jpg)
Dedicated to Professor Frank A. L. Anet on the occasion of his 90th birthday.
Abstract
This account provides an overview of results from experimental studies motivated by an ongoing search for the origin of RNA. Twenty-five years ago, I became fascinated by the possibility that the origin of life was facilitated by an enzyme-free, prebiotic form of the polymerase chain reaction (PCR); a process potentially enabled by molecular self-assembly and driven by an oscillating environment on the early Earth. After numerous unsuccessful attempts to assemble the mononucleotides of extant RNA, I embraced the hypothesis that RNA is a product of chemical or biological evolution, which eventually led to the identification of candidate molecules for the nucleobases of proto-RNA (the ancestor of RNA). These heterocycles self-assemble as monomers in water, are found in carbonaceous chondrites, are produced in model prebiotic reactions, and readily react with ribose to form nucleosides. This progress toward finding a plausible prebiotic synthesis of a hypothetical proto-RNA illustrates how origins research can lead to exciting and unexpected chemistries, particularly when chemical models are subjected to rigorous experimentation and regular revision in response to positive and negative results.
1 Inspiration and Initial Thoughts on the Origin of RNA
2 The Guidance and Influence of Professor Frank A. L. Anet
3 Proposing a Hypothetical, but Chemically Sound, Origin of RNA
4 Experimental Studies of Intercalation-Mediated Assembly and Synthesis
5 Considering Purine–Purine Base Pairs Before Watson–Crick
6 Considering Pyrimidine/Triazine Proto-Nucleobases
7 Addressing The Nucleoside Problem; a Bonus
8 Prebiotic Polymerization and Replication, On the Next Horizon?
9 Conclusions and Reflections
-
References
- 1a Woese C. The Evolution of the Genetic Code . In The Genetic Code . Harper & Row; New York: 1967: 179-195
- 1b Crick FH. C. J. Mol. Biol. 1968; 38: 367
- 1c Orgel LE. J. Mol. Biol. 1968; 38: 381
- 2a Kruger K, Grabowski PJ, Zaug AJ, Sands J, Gottschling DE, Cech TR. Cell 1982; 31: 147
- 2b Guerriertakada C, Gardiner K, Marsh T, Pace N, Altman S. Cell 1983; 35: 849
- 3a Tuerk C, Gold L. Science 1990; 249: 505
- 3b Ellington A, Szostak J. Nature 1990; 346: 818
- 3c Robertson DL, Joyce GF. Nature 1990; 344: 467
- 4a Gilbert W. Nature 1986; 319: 618
- 4b Westheimer FH. Nature 1986; 319: 534
- 4c Gesteland RF, Atkins JF. The RNA World. The Nature of Modern RNA Suggests a Prebiotic RNA World . 1st ed. Cold Spring Harbor Laboratory Press; Cold Spring Harbor (NY): 1993
- 5 Joyce GF. Nature 1989; 338: 217
- 6a Hud N, Milanovich F, Balhorn R. Biochemistry 1994; 33: 7528
- 6b Hud NV, Allen MJ, Downing KH, Lee J, Balhorn R. Biochem. Biophys. Res. Commun. 1993; 193: 1347
- 7 Bernal JD. Proc. Phys. Soc. London, Sect. A 1949; 62: 537
- 8 Österber R, Orgel L, Lohrmann R. J. Mol. Evol. 1973; 2: 231
- 9 Engelhart AE, Hud NV. Cold Spring Harb. Perspect. Biol. 2010; 2: a002196
- 10 Woese CR. Proc. Natl. Acad. Sci. USA 2002; 99: 8742
- 11 Ts’o PO. P. Bases, Nucleosides, and Nucleotides . In Basic Principles in Nucleic Acid Chemistry . Vol. 1. Ts’o PO. P. Academic Press; New York: 1974: 453-584
- 12 Hoogsteen K. Acta Crystallogr. 1959; 12: 822
- 13a O’Brien EJ. Acta Crystallogr. 1967; 23: 92
- 13b Simundza G, Sakore TD, Sobell HM. J. Mol. Biol. 1970; 48: 263
- 13c O’Brien EJ. J. Mol. Biol. 1966; 22: 377
- 14 Guillon D. Columnar Order in Thermotropic Mesophases . In Liquid Crystals II . Mingos DM. P. Springer-Verlag; New York: 1999: 41-82
- 15 Lehrman EA, Crothers DM. Nucleic Acids Res. 1977; 4: 1381
- 16 Smith FW, Feigon J. Nature 1992; 356: 164
- 17 Anet FA. L, Bourn AJ. R. J. Am. Chem. Soc. 1965; 87: 5250
- 18 Joyce GF, Schwartz AW, Miller SL, Orgel LE. Proc. Natl. Acad. Sci. USA 1987; 84: 4398
- 19 Ferris JP, Hill AR, Liu RH, Orgel LE. Nature 1996; 381: 59
- 20 Hud NV, Anet FA. L. J. Theor. Biol. 2000; 205: 543
- 21 Scott J. Histochemie 1972; 30: 215
- 22a Jain SS, Polak M, Hud NV. Nucleic Acids Res. 2003; 31: 4608
- 22b Persil Ö, Santai CT, Jain SS, Hud NV. J. Am. Chem. Soc. 2004; 126: 8644
- 22c Xing F, Song G, Ren J, Chaires JB, Qu X. FEBS Lett. 2005; 579: 5035
- 23a Cafferty BJ, Musetti C, Kim K, Horowitz ED, Krishnamurthy R, Hud NV. Chem. Commun. 2016; 52: 5436
- 23b Jain SS, Anet FA. L, Stahle CJ, Hud NV. Angew. Chem. Int. Ed. 2004; 43: 2004
- 23c Horowitz ED, Engelhart AE, Chen MC, Quarles KA, Smith MW, Lynn DG, Hud NV. Proc. Natl. Acad. Sci. USA 2010; 107: 5288
- 24a Mergny JL, Duval-Valentin G, Nguyen CH, Perrouault L, Faucon B, Rougee M, Montenay-Garestier T, Bisagni E, Helene C. Science 1992; 256: 1681
- 24b Wilson WD, Tanious FA, Mizan S, Yao SJ, Kiselyov AS, Zon G, Strekowski L. Biochemistry 1993; 32: 10614
- 24c Kan YZ, Armitage B, Schuster GB. Biochemistry 1997; 36: 1461
- 24d Ren JS, Chaires JB. Biochemistry 1999; 38: 16067
- 25 Polak M, Hud NV. Nucleic Acids Res. 2002; 30: 983
- 26 Avakyan N, Greschner AA, Aldaye F, Serpell CJ, Toader V, Petitjean A, Sleiman HF. Nat. Chem. 2016; 8: 368
- 27 Li JJ, Xi Q, Du WF, Yu RQ, Jiang JH. Analyst 2016; 141: 2384
- 28 Guo CL, Wang K, Zerah-Harush E, Hamill J, Wang B, Dubi Y, Xu BQ. Nat. Chem. 2016; 8: 484
- 29 Hud NV, Jain SS, Li X, Lynn DG. Chem. Biodivers. 2007; 4: 768
- 30 Eschenmoser A. Angew. Chem. Int. Ed. 2011; 50: 12412
- 31 Yang Y.-W, Zhang S, McCullum EO, Chaput JC. J. Mol. Evol. 2007; 65: 289
- 32 Giannaris PA, Damha MJ. Nucleic Acids Res. 1993; 21: 4742
- 33 Karri P, Punna V, Kim K, Krishnamurthy R. Angew. Chem. Int. Ed. 2013; 52: 5840
- 34 Orgel LE. TIBS 1998; 23: 491
- 35 Fuller WD, Sanchez RA, Orgel LE. J. Mol. Evol. 1972; 1: 249
- 36 Rich A. Nature 1958; 181: 521
- 37 Howard FB, Miles HT. Biochemistry 1977; 16: 4647
- 38 Roberts C, Chaput JC, Switzer C. Chem. Biol. 1997; 4: 899
- 39a Heuberger BD, Switzer C. ChemBioChem 2008; 9: 2779
- 39b Battersby TR, Albalos M, Friesenhahn MJ. Chem. Biol. 2007; 14: 525
- 40 Callahan MP, Smith KE, Cleaves HJ, Ruzicka J, Stern JC, Glavin DP, House CH, Dworkin JP. Proc. Natl. Acad. Sci. USA 2011; 108: 13995
- 41 Buckley R, Enekwa CD, Williams LD, Hud NV. ChemBioChem 2011; 12: 2155
- 42 Kuruvilla E, Schuster GB, Hud NV. ChemBioChem 2013; 14: 45
- 43a Albert A, Brown DJ. J. Chem. Soc. 1954; 2060
- 43b O’Neil MJ. The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals. 14th ed. Merck; New Jersey: 2006
- 44 Hattori M, Frazier J, Miles HT. Biopolymers 1976; 15: 523
- 45 Hattori M, Frazier J, Miles HT. Biopolymers 1975; 14: 2095
- 46 Engelhart AE, Morton TH, Hud NV. Chem. Commun. 2009; 647
- 47 Cafferty BJ, Avirah RR, Schuster GB, Hud NV. Chem. Sci. 2014; 5: 4681
- 48 Cafferty BJ, Hud NV. I sr. J. Chem. 2015; 55: 891
- 49a Hayatsu R, Studier MH, Moore LP, Anders E. Geochim. Cosmochim. Acta 1975; 39: 471
- 49b Harvey GR, Degens ET, Mopper K. Naturwissenschaften 1971; 58: 624
- 49c Hayatsu R, Studier MH, Oda A, Fuse K, Anders E. Geochim. Cosmochim. Acta 1968; 32: 175
- 50 Bean HD, Sheng YH, Collins JP, Anet FA. L, Leszczynski J, Hud NV. J. Am. Chem. Soc. 2007; 129: 9556
- 51 Seto CT, Whitesides GM. J. Am. Chem. Soc. 1990; 112: 6409
- 52a Borzo M, Detellier C, Laszlo P, Paris A. J. Am. Chem. Soc. 1980; 102: 1124
- 52b Detellier C, Laszlo P. J. Am. Chem. Soc. 1980; 102: 1135
- 52c Hud NV, Schultze P, Sklenar V, Feigon J. J. Mol. Biol. 1999; 285: 233
- 52d Hud NV, Smith FW, Anet FA. L, Feigon J. Biochemistry 1996; 35: 15383
- 53a Huang DM, Geissler PL, Chandler D. J. Phys. Chem. B 2001; 105: 6704
- 53b Raschke TM, Tsai J, Levitt M. Proc. Natl. Acad. Sci. USA 2001; 98: 5965
- 53c Chandler D. Nature 2005; 437: 640
- 54 Bielejewska AG, Marjo CE, Prins LJ, Timmerman P, de Jong F, Reinhoudt DN. J. Am. Chem. Soc. 2001; 123: 7518
- 55 Lehn JM, Mascal M, Decian A, Fischer J. J. Chem. Soc., Perkin Trans. 2 1992; 461
- 56 van Vliet MJ, Visscher J, Schwartz AW. J. Mol. Evol. 1995; 41: 257
- 57 Cafferty BJ, Gallego I, Chen MC, Farley KI, Eritja R, Hud NV. J. Am. Chem. Soc. 2013; 135: 2447
-
58 De Greef TF, Smulders MM, Wolffs M, Schenning AP, Sijbesma RP, Meijer EW. Chem. Rev. 2009; 109: 5687
- 59 Li C, Cafferty BJ, Karunakaran SC, Schuster GB, Hud NV. Phys. Chem. Chem. Phys. 2016; 18: 20091
- 60 Krishnamurthy R. Acc. Chem. Res. 2012; 45: 2035
- 61a Cafferty BJ, Hud NV. Curr. Opin. Chem. Biol. 2014; 22: 146
- 61b Hud NV, Cafferty BJ, Krishnamurthy R, Williams LD. Chem. Biol. 2013; 20: 466
- 62 Orgel LE. Crit. Rev. Biochem. Mol. Biol. 2004; 39: 99
- 63 Kolb VM, Dworkin JP, Miller SL. J. Mol. Evol. 1994; 38: 549
- 64 Gildea B, McLaughlin LW. Nucleic Acids Res. 1989; 17: 2261
- 65 Larralde R, Robertson MP, Miller SL. Proc. Natl. Acad. Sci. USA 1995; 92: 8158
- 66 Chen MC, Cafferty BJ, Mamajanov I, Gállego I, Khanam J, Krishnamurthy R, Hud NV. J. Am. Chem. Soc. 2014; 136: 5640
- 67a Gonzalez MA, Requejo JL. J, Albarran JC. P, Perez JA. G. Carbohydr. Res. 1986; 158: 53
- 67b Wulff G, Clarkson G. Carbohydr. Res. 1994; 257: 81
- 68 Cafferty BJ, Fialho DM, Khanam J, Krishnamurthy R, Hud NV. Nat. Commun. 2016; 7: 11328
- 69 Menor-Salvan C, Ruiz-Bermejo DM, Guzman MI, Osuna-Esteban S, Veintemillas-Verdaguer S. Chem. Eur. J. 2009; 15: 4411
- 70 Hayatsu R, Studier MH, Oda A, Fuse K, Anders E. Geochim. Cosmochim. Acta 1968; 32: 175
- 71 Walker SI, Grover MA, Hud NV. PLoS ONE 2012; 7: e34166
- 72 Bean HD, Anet FA. L, Gould IR, Hud NV. Orig. Life Evol. Biosph. 2006; 36: 39
- 73a Mamajanov I, MacDonald PJ, Ying J, Duncanson DM, Dowdy GR, Walker CA, Engelhart AE, Fernández FM, Grover MA, Hud NV, Schork FJ. Macromolecules 2014; 47: 1334
- 73b Forsythe JG, Yu SS, Mamajanov I, Grover MA, Krishnamurthy R, Fernandez FM, Hud NV. Angew. Chem. Int. Ed. 2015; 54: 9871
- 74 Burcar B, Pasek M, Gull M, Cafferty BJ, Velasco F, Hud NV, Menor-Salván C. Angew. Chem. Int. Ed. 2016; 55: 13249
- 75 He C, Gállego I, Laughlin B, Grover MA, Hud NV. Nat. Chem. 2016; in press; DOI: 10.1038/nchem.2628.
- 76 Orgel LE, Crick FH. C. FASEB J. 1993; 7: 238
- 77 Kim HJ, Benner SA. Astrobiology 2015; 15: 301
- 78 Powner MW, Gerland B, Sutherland JD. Nature 2009; 459: 239