Evidence for an "RNA world," an episode of life on Earth during which RNA was the only genetically encoded component of biological catalysts, is found in the ribosome (1), catalytic RNA molecules (2), and contemporary metabolism (3). That RNA could form spontaneously and persist under prebiotic conditions has been doubted, however (4,5). Ribose and its sister pentoses (arabinose, xylose, and lyxose) are made under alkaline conditions from simple organic precursors (formaldehyde and glycolaldehyde) (6) known in interstellar space and presumably available on early Earth (7). Pentoses do not accumulate under these conditions, however; they rapidly decompose in a "browning" reaction to generate largely undescribable polymeric mixtures.Because borate forms complexes with organic molecules (such as pentoses) that carry 1,2-dihydroxyl groups, pentoses might accumulate if borate were present. Borate should not prevent the addition of the enolate of glycolaldehyde 1 (reacting as a nucleophile) with formaldehyde 2 (reacting as an electrophile) to form glyceraldehyde 3 ( Fig. 1). As the first compound in the sequence to have a 1,2-diol, however, 3 should complex with borate. Because the complex is anionic, enolization of 3 should be suppressed, preventing 3 from acting as a nucleophile. Compound 3 should still serve as an electrophile, however, reacting with the enediolate of 1 to give pentoses (4 to 7), including ribose 4.Once formed, the cyclic forms of the pentoses should form stable, less reactive complexes with borate (8 to 11), because the cyclic complexes lack CϭO groups (fig. S1). Our experiments supported this. Whereas ribose decomposed in minutes under alkaline conditions, it remained stable for days at room temperature in the presence of borate (figs. S2 and S3).Next, we asked whether the presence of borate is compatible with ribose synthesis. With Ca(OH) 2 (0.5 M suspension; pH ϳ12; 25°and 45°C), a solution of 1 and 3 (each 0.5 mM) turned brown (1 hour and 10 min, respectively). Small but detectable amounts of pentoses were found after 20 min at 45°C. These were detected after derivatization with N,O-bis(trimethylsilyl)-trifluoroacetamide by gas chromatography-mass spectrometry (GC-MS) ( fig. S4). Pentoses were nearly gone after a 1 hour incubation.When the same incubation was done with borate minerals ulexite (NaCaB 5 O 9 ⅐8H 2 O), kernite (Na 2 B 4 O 7 ), or colemanite (Ca 2 B 6 O 11 ⅐5H 2 O) in synthetic form, the solution did not turn brown, even after incubation for 2 months (Fig. 1). To demonstrate the synthesis of pentoses under these conditions, the mixture was acidified (pH 5), filtered, and freeze-dried. Borate was removed as its trimethyl ester by evaporation two times with methanol and evacuation, and the sugars were derivatized. The presence of arabinose, lyxose, xylose, and ribose in similar amounts was confirmed by coinjection of authentic standards ( fig. S5). Pentoses constituted the large majority of total carbon. Formation of ribose/ribulose was confirmed by treating the mixture with sodium b...

One present obstacle to the "RNA-first" model for the origin of life is an inability to generate reasonable "hands off" scenarios for the formation of carbohydrates under conditions where they might have survived for reasonable times once formed. Such scenarios would be especially compelling if they deliver pent(ul)oses, five-carbon sugars found in terran genetics, and exclude other carbohydrates (e.g., aldotetroses) that may also be able to function in genetic systems. Here, we provide detailed chemical analyses of carbohydrate premetabolism, showing how borate, molybdate, and calcium minerals guide the formation of tetroses (C(4)H(8)O(4)), heptoses (C(7)H(14)O(7)), and pentoses (C(5)H(10)O(5)), including the ribose found in RNA, in "hands off" experiments, starting with formaldehyde and glycolaldehyde. These results show that pent(ul)oses would almost certainly have formed as stable borate complexes on the surface of an early Earth beneath a humid CO(2) atmosphere suffering electrical discharge. While aldotetroses form extremely stable complexes with borate, they are not accessible by pathways plausible under the most likely early Earth scenarios. The stabilization by borate is not, however, absolute. Over longer times, material is expected to have passed from borate-bound pent(ul)oses to a branched heptulose, which is susceptible to Cannizzaro reduction to give dead end products. We show how this fate might be avoided using molybdate-catalyzed rearrangement of a branched pentose that is central to borate-moderated cycles that fix carbon from formaldehyde. Our emerging understanding of the nature of the early Earth, including the presence of hydrated rocks undergoing subduction to form felsic magmas in the early Hadean eon, may have made borate and molydate species available to prebiotic chemistry, despite the overall "reduced" state of the planet.

No abstract

The development of a sequence-general nucleic acid copying system is an essential step in the assembly of a synthetic protocell, an autonomously replicating spatially localized chemical system capable of spontaneous Darwinian evolution. Previously described nonenzymatic template-copying experiments have validated the concept of nonenzymatic replication, but have not yet achieved robust, sequence-general polynucleotide replication. The 5′-phosphorimidazolides of the 2′-amino-2′,3′-dideoxyribonucleotides are attractive as potential monomers for such a system because they polymerize by forming 2′→5′ linkages, which are favored in nonenzymatic polymerization reactions using similarly activated ribonucleotides on RNA templates. Furthermore, the 5′-activated 2′-amino nucleotides do not cyclize. We recently described the rapid and efficient nonenzymatic copying of a DNA homopolymer template (dC15) encapsulated within fatty acid vesicles using 2′-amino-2′,3′-dideoxyguanosine−5′-phosphorimidazolide as the activated monomer. However, to realize a true Darwinian system, the template-copying chemistry must be able to copy most sequences and their complements to allow for the transmission of information from generation to generation. Here, we describe the copying of a series of nucleic acid templates using 2′-amino-2′,3′-dideoxynucleotide−5′-phosphorimidazolides. Polymerization reactions proceed rapidly to completion on short homopolymer RNA and LNA templates, which favor an A-type duplex geometry. We show that more efficiently copied sequences are generated by replacing the adenine nucleobase with diaminopurine, and uracil with C5-(1-propynyl)uracil. Finally, we explore the copying of longer, mixed-sequence RNA templates to assess the sequence-general copying ability of 2′-amino-2′,3′-dideoxynucleoside−5′-phosphorimidazolides. Our results are a significant step forward in the realization of a self-replicating genetic polymer compatible with protocell template copying and suggest that N2′→P5′-phosphoramidate DNA may have the potential to function as a self-replicating system.