Constraints On The Emergence Of RNA Through Non-Templated Primer Extension With Mixtures Of Potentially Prebiotic Nucleotides

The emergence of RNA on the early Earth is likely to have been influenced by a series of chemical and physical processes that acted to filter out various alternative nucleic acids. For example, UV photostability is thought to have favored the survival of the canonical nucleotides.

In a recent proposal for the prebiotic synthesis of the building blocks of RNA, ribonucleotides share a common pathway with arabino- and threo-nucleotides. We have therefore investigated non-templated primer extension with 2-aminoimidazole-activated forms of these alternative nucleotides to see if the synthesis of the first oligonucleotides might have been biased in favor of RNA.

We show that non-templated primer extension occurs predominantly through 5ʹ-5ʹ imidazolium bridged dinucleotides, echoing the mechanism of template-directed primer extension. Ribo- and arabino-nucleotides exhibited comparable rates and yields of non-templated primer extension, whereas threo-nucleotides showed lower reactivity. Competition experiments with mixtures of nucleotides confirmed the bias against the incorporation of threo-nucleotides into oligonucleotides.

This bias, coupled with selective prebiotic synthesis and templated copying favoring ribonucleotides, provides a plausible model for the exclusion of threo-nucleotides from primordial oligonucleotides. In contrast, the exclusion of arabino-nucleotides may have resulted primarily from biases in synthesis and in template-directed primer extension.

Xiwen Jia, Stephanie J. Zhang, Lijun Zhou, Jack W. Szostak

Constraints on the Emergence of RNA through Non-Templated Primer Extension with Mixtures of Potentially Prebiotic Nucleotides
doi: https://doi.org/10.1101/2024.01.21.576316

Astrobiology, genomics,