Emergence of the First Catalytic Oligonucleotides in a Formamide‐Based Origin Scenario

Abstract

50 years after the historical Miller-Urey experiment, the formamide-based scenario is perhaps the most powerful concurrent hypothesis for the origin of life on our planet besides the traditional HCN-based concept. The information accumulated during the last 15 years in this topic is astonishingly growing and nowadays the formamide-based model represents one of the most complete and coherent pathways leading from simple prebiotic precursors up to the first catalytically active RNA molecules. In this work, we overview the major events of this long pathway that have emerged from recent experimental and theoretical studies, mainly concentrating on the mechanistic, methodological, and structural aspects of this research.

Stability of 2′,3′ and 3′,5′ cyclic nucleotides in formamide and in water: a theoretical insight into the factors controlling the accumulation of nucleic acid building blocks in a prebiotic pool

“…20,23 A plausible geological context for our formamide-model described herein and in Ref. 23 is a pool on top of a stable, geologically active region, which undergoes rapid cooling upon heavy raining.…”

“…20,23 The simple formamide-based origin scenario we outlined in Ref. 23 suggests a non-equilibrium solution for the origin of life where different chemical steps take place consecutively under different conditions (see Figure 6). Figure 6.…”

“…Indeed, the formamide-based synthesis experiments of prebiotic building blocks has commonly been conducted at 433 K. 7 More detailed explanation of the potential prebiotic relevance of the temperature range can be found, e.g., in our preceding review paper (see also below). 23 Note that such conditions are considered as a relevant context for prebiotic processes on early Earth not only by us 23 but also, e.g., by the so called "discontinuous synthesis model" of the origin of life advocated by the Benner group; 17,18 for another independent latest research highlight see Ref. 21.…”

“…Temperature-driven chemical evolution. 23 Prebiotic synthesis could occur under appropriate sequences of temperature drops in the primordial environment. These could push through those chemical transformations which could lead to more and more complex molecular entities.…”

“…[17][18][19][20][21][22] We will show that while aqueous solutions and lower temperatures could favor accumulation of 2',3' cyclic nucleotides over that of the 3',5' cyclic form, at higher temperatures and in formamide solvent 3',5' cyclic nucleotides are the thermodynamically preferred species. Thus, after a temperature drop, 23 initial cycles of polymerization leading to the first RNA molecules could indeed occur in a 3',5'-cyclic-nucleotide rich environment.…”