Abiogenesis

Abstract

Nonenzymatic assembly of RNA from chemically activated building blocks, such as phosphorimidazolides, would have been essential for the emergence of ribozymes on the early Earth. We previously showed that ribonucleoside monophosphates can be activated to phosphorimidazolides via a potentially prebiotic phospho-Passerini reaction involving 2-aminoimidazole, 2-methylbutyraldehyde, and methyl isocyanide, and that these activated nucleotides enable template-directed nonenzymatic RNA polymerization in the same reaction mixture. Here, we demonstrate that the same chemistry activates oligoribonucleotides and drives both nonenzymatic and ribozyme-catalyzed RNA ligation within the same reaction environment. By demonstrating a continuous path from prebiotic activation chemistry to RNA template copying by both nonenzymatic and ribozyme-catalyzed ligation, our results provide a more integrated and realistic model for primordial RNA assembly.

Abstract

Estimating the plausibility of RNA self-reproduction is central to origin-of-life scenarios. However, this property has been shown in only a handful of catalytic RNAs. Here, we compare models for their generative power in diversifying a reference ribozyme, based on statistical covariation and secondary structure prediction, and experimentally test model predictions using high-throughput sequencing. Leveraging statistical physics methods, we compute the number of ribozymes capable of autocatalytic self-reproduction from oligonucleotide fragments to be over 1039, with sequences found up to 65 mutations from the original sequence and 99 mutations away from each other, far beyond the 10 mutations achieved by deep mutational scanning. The findings demonstrate an efficient method for exploring RNA sequence space, and provide quantitative data on self-reproducing RNA that further illuminates the potential pathways to abiogenesis.

Abstract

The concept of chemically evolvable replicators is central to abiogenesis. Chemical evolvability requires three essential components: energy-harvesting mechanisms for nonequilibrium dissipation, kinetically asymmetric replication and decomposition pathways, and structure-dependent selective templating in the autocatalytic cycles. We observed a UVA light-fueled chemical system displaying sequence-dependent replication and replicator decomposition. The system was constructed with primitive peptidic foldamer components. The photocatalytic formation–recombination cycle of thiyl radicals was coupled with the molecular recognition steps in the replication cycles. Thiyl radical-mediated chain reaction was responsible for the replicator death mechanism. The competing and kinetically asymmetric replication and decomposition processes led to light intensity-dependent selection far from equilibrium. Here, we show that this system can dynamically adapt to energy influx and seeding. The results highlight that mimicking chemical evolution is feasible with primitive building blocks and simple chemical reactions.

First part of a three-part series about the origin of life, given by Nobel Prize winner Jack Szostak.

A fascinating topic. The lectures are a bit old, but the information is not outdated.

Part 2

Part 3

These lectures come from iBiology, a non-profit that produces educational content and releases it under a creative commons license.

Some of my co-workers study the origin of life, and part of their work focuses on pre-biotic peptide synthesis.

I am convinced that nucleotides appeared well before protein synthesis, and that protein synthesis appears at a mature stage during life's evolution, likely catalyzed by ribozymes... So I don't think that pre-biotic peptide synthesis is relevant for the origin of life!

I am making an effort to study the alternative hypotheses in which life has a proteomic origin. My opinion is still unchanged, but I found this article interesting because at least it proposes a somewhat viable model.

Do you have any opinions about the origin of life?