A Prebiotic Selection of β-Furanoside-5'-Phosphate as the Sole Configuration toward the Synthesis of Extant RNA

20 December 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


The cause of the selection of β-furanoside-5'-phosphate as the backbone configuration of RNA during life’s origins has not been fully determined. Previous attempts were mostly unsuccessful in demonstrating either a selective synthesis or a selection mechanism for β-furanoside and 5'-nucleotide in the nucleosidation and phosphorylation steps. These questions are answered in this study. Inspired by the chromatographic elution order of nucleoside and nucleotide isomers, a unique separation mechanism has been established. It is discovered that β-furanoside is the most permeable configurational isomer across a lipid protomembrane as compared with other isomers, and becomes the most abundant isomer through permeation. In the meantime, phosphate can be transported across the lipid membrane and preserved inside the protocell in its soluble form, thereby circumventing its abundance and availability issues. The phosphorylation step is likely to take place intracellularly, where the formed nucleotide isomers are again screened by the lipid membrane via a reverse permeation, leaving 5'-nucleotide the enriched ribonucleotide species in the protocell for the upcoming transformations such as oligomerization. These findings depict a primitive selection mechanism driven by physicochemical forces to advance critical steps in molecular evolution, which could be one of the earliest protocellular functions.


origins of life
RNA world
prebiotic chemistry

Supplementary materials

Supplementary Materials
Experimental Procedures and Chromatographic Data


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