Wet–dry cycles cause nucleic acid monomers to polymerize into long chains

The key first step in the oligomerization of monomers is to find an initiator, which is usually done by thermolysis or photolysis. We present a markedly different approach that initiates acid-catalyzed polymerization at the surface of water films or water droplets, which is the reactive phase during a wet-dry cycle in freshwater hot springs associated with subaerial volcanic landmasses. We apply this method to the oligomerization of different nucleic acids, a topic relevant to how it might be possible to go from simple nucleic acid monomers to long-chain polymers, a key step in forming the building blocks of life. It has long been known that dehydration at elevated temperatures can drive the synthesis of ester and peptide bonds, but this reaction has typically been carried out by incubating dry monomers at elevated temperatures. We report that single or multiple cycles of wetting and drying link mononucleotides by forming phosphodiester bonds. Mass spectrometric analysis reveals uridine monophosphate oligomers up to 53 nucleotides, with an abundance of 35 and 43 nt in length. Long-chain oligomers are also observed for thymidine monophosphate, adenosine monophosphate, and deoxyadenosine monophosphate after exposure to a few wet-dry cycles. Nanopore sequencing confirms that long linear chains are formed. Enzyme digestion shows that the linkage is the phosphodiester bond, which is further confirmed by