Escalation of polymerization in a thermal gradient

Abstract

For the emergence of early life, the formation of biopolymers such as RNA is essential. However, the addition of nucleotide monomers to existing oligonucleotides requires millimolar concentrations. Even in such optimistic settings, no polymerization of RNA longer than about 20 bases could be demonstrated. How then could self-replicating ribozymes appear, for which recent experiments suggest a minimal length of 200 nt? Here, we demonstrate a mechanism to bridge this gap: the escalated polymerization of nucleotides by a spatially confined thermal gradient. The gradient accumulates monomers by thermophoresis and convection while retaining longer polymers exponentially better. Polymerization and accumulation become mutually self-enhancing and result in a hyperexponential escalation of polymer length. We describe this escalation theoretically under the conservative assumption of reversible polymerization. Taking into account the separately measured thermophoretic properties of RNA, we extrapolate the results for primordial RNA polymerization inside a temperature gradient in pores or fissures of rocks. With a dilute, nanomolar concentration of monomers the model predicts that a pore length of 5 cm and a temperature difference of 10 K suffice to polymerize 200-mers of RNA in micromolar concentrations. The probability to generate these long RNAs is raised by a factor of >10 600 compared with polymerization in a physical equilibrium. We experimentally validate the theory with the reversible polymerization of DNA blocks in a laser-driven thermal trap. The results confirm that a thermal gradient can significantly enlarge the available sequence space for the emergence of catalytically active polymers. molecular evolution | nonequilibrium | RNA world | (nonenzymatic) emergence of RNA | hydrothermal vents P olymers are the vital building blocks of all known life forms. According to the central dogma of molecular biology (1), DNA stores the information for how and when to build proteins, which for their part carry out catalytic tasks like the polymerization of DNA. How this self-perpetuating cycle has started is unknown. The RNA-world hypothesis posits that RNA molecules were the central players in prebiotic evolution, because they exhibit both a catalytic function similar to that of proteins and the information storage capabilities of DNA (2). However, how could such an RNA world have emerged from the prebiotic soup?A key element of the RNA world is a ribozyme that catalyzes RNA replication. Directed in vitro evolution and engineering have shown that such ribozymes exist, but require a length of 200 bases or more, even in favorable high-salt conditions (3). Starting from chemical nonequilibrium conditions with millimolar concentrations of energy-rich nucleotides (4-6) and with the help of catalytic surfaces (7), only the formation of much shorter polynucleotides on the order of 20 bases was demonstrated in the laboratory. Slow kinetics and cleavage due to hydrolysis limit the formation of long polynucleotides and finally lead...

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