Oligomerization of Non‐Activated Nucleotides Under Hot Acidic Wet–Dry Cycling Without Catalytic Agents

ABSTRACT The emergence of genetic polymers such as RNA and DNA from prebiotically available building blocks represents a key step toward the origin of life. Nucleotides, the building blocks of RNA and DNA, may have existed on the prebiotic Earth, but their oligomerization is energetically unfavorable in aqueous solution. Consequently, chemically activated nucleotides and/or catalytic agents have typically been invoked. The extent of oligomerization of non‐activated nucleotides is sensitive to experimental subtleties, and detection uncertainties and potential artefacts complicate its interpretation. Further clarification is therefore required. Here, we present experimental evidence for the oligomerization of non‐activated RNA and DNA nucleotides in hot, acidic wet‐dry cycling environments, resembling a simplified model of geothermal pools on the prebiotic Earth. No catalytic agents were added, and pH was naturally buffered by the nucleotides, minimizing external interferences. The resulting oligonucleotides were short (≤4 nt), with yields up to ∼3%. While previous studies under similar conditions usually employ catalytic agents such as minerals, lipids, or salts, our findings demonstrate that phosphodiester bonds form in their absence. However, generating and sustaining long, genetically capable polymers in acidic hot wet‐dry cycling environments remains challenging.