A model for the emergence of RNA from a prebiotically plausible mixture of ribonucleotides, arabinonucleotides and 2’-deoxynucleotides

Abstract

The abiotic synthesis of ribonucleotides is thought to have been an essential step towards the emergence of the RNA world. However, it is likely that the prebiotic synthesis of ribonucleotides was accompanied by the simultaneous synthesis of arabinonucleotides, 2′-deoxyribonucleotides, and other variations on the canonical nucleotides. In order to understand how relatively homogeneous RNA could have emerged from such complex mixtures, we have examined the properties of arabinonucleotides and 2′-deoxyribonucleotides in nonenzymatic template-directed primer extension reactions. We show that nonenzymatic primer extension with activated arabinonucleotides is much less efficient than with activated ribonucleotides, and furthermore that once an arabinonucleotide is incorporated, continued primer extension is strongly inhibited. As previously shown, 2′-deoxyribonucleotides are also less efficiently incorporated in primer extension reactions, but the difference is more modest. Experiments with mixtures of nucleotides suggest that the coexistence of ribo- and arabino-nucleotides does not impede the copying of RNA templates. Moreover, chimeric oligoribonucleotides containing 2′-deoxy- or arabino-nucleotides are effective templates for RNA synthesis. We propose that the initial genetic polymers were random sequence chimeric oligonucleotides formed by untemplated polymerization, but that template copying chemistry favored RNA synthesis; multiple rounds of replication may have led to pools of oligomers composed mainly of RNA.

Non-enzymatic primer extension with strand displacement

“…and heterogeneous oligonucleotides that could have coexisted alongside oligoribonucleotides could also promote strand displacement via the formation of invaders. Recent work in our lab (Kim et al, 2019) has shown that oligonucleotides ending in a 3′-arabino nucleotide cannot be further extended, providing a mechanism for the generation of short invaders that are inert to copying chemistry. Thus, the products of both degradative reactions and stalled replicative processes could contribute an essential function to genomic replication.…”

Structural interpretation of the effects of threo-nucleotides on nonenzymatic template-directed polymerization

“…RNA has an exceptional double helical structure with the ribose sugars in the 3’- endo conformation; as a consequence the RNA primer/template/intermediate complex is preorganized so as to favour rapid primer extension. Our experiments show that in this context, RNA copying has a significant kinetic advantage over alternative nucleic acids including not only TNA, but also ANA and DNA(26). Our experimental results are therefore consistent with a model in which relatively homogeneous RNA oligonucleotides emerged from a much more heterogeneous mixture of activated nucleotides through the self-purifying capacity of nonenzymatic RNA replication.…”

“…We therefore attempted to observe the formation of the corresponding TNA dinucleotide intermediate under primer extension conditions (Figure 2C). When we incubated purified 2AIptC at a concentration of 60 mM at pH 8 and followed the reaction by 31P-NMR, we found that the imidazolium-bridged TNA dinucleotide is formed, but the observed rate of 8.8 * 10 -4 hr -1 mM -1 is approximately 4 to 5 fold slower than the corresponding rates for the activated ribonucleotides 2AI-rA and 2AI-rC (3.2 and 4.5 * 10 -3 hr -1 mM -1 )(26,27) (Figure 2D). This result suggests that the slow rate of primer extension with activated threo-nucleotide monomers is due at least in part to the slower formation of the necessary imidazolium-bridged intermediate.…”

“…The largest deviations between the two structures are at the primer terminus, where the tG residue is shifted and twisted compared to the native RNA primer, with distances in the range of 1.5 - 2.4 Å between the corresponding atoms of the threose and ribose sugar rings (Figure 6E). The tG residue has a glycosidic linkage torsion X angle of −121° (Table 1), compared to a typical X angle of −168° for the ribonucleotides of the primer(26).…”

Ecological and Biotechnological Aspects of Pigmented Microbes: A Way Forward in Development of Food and Pharmaceutical Grade Pigments

“…Since protocells’ origin, natural pigments have transformed into various phenomena such as pigments, fluorescence, and bioluminescence, found in prokaryotes and eukaryotes. Currently, researchers believe that life had originated 4.5 billion years ago from the extreme environment like hydrothermal vents in the ocean [ 130 ] or warm water pools in the volcanic land or geothermal (hot spring) areas [ 129 , 131 , 132 ], based on the evidences of hypothetic protocell structures, i.e., vesicles formed by simple fatty acids [ 130 ] and proteins [ 133 ], RNA [ 131 ] and DNA molecules [ 129 ]. The abundant external red pigments seen in deep-sea tubeworms at hydrothermal vents are indeed hemoglobins that act as binding sites to oxygen and hydrogen sulfide and transport these molecules to internal bacterial symbionts [ 134 ].…”