Abstract

The evolutionary origin of the genome remains elusive. Here, I hypothesize that its first iteration, the protogenome, was a multi-ribozyme RNA. It evolved, likely within liposomes (the protocells) forming in dry-wet cycling environments, through the random fusion of ribozymes by a ligase and was amplified by a polymerase. The protogenome thereby linked, in one molecule, the information required to seed the protometabolism (a combination of RNA-based autocatalytic sets) in newly forming protocells. If this combination of autocatalytic sets was evolutionarily advantageous, the protogenome would have amplified in a population of multiplying protocells. It likely was a quasispecies with redundant information, e.g., multiple copies of one ribozyme. As such, new functionalities could evolve, including a genetic code. Once one or more components of the protometabolism were templated by the protogenome (e.g., when a ribozyme was replaced by a protein enzyme), and/or addiction modules evolved, the protometabolism became dependent on the protogenome. Along with increasing fidelity of the RNA polymerase, the protogenome could grow, e.g., by incorporating additional ribozyme domains. Finally, the protogenome could have evolved into a DNA genome with increased stability and storage capacity. I will provide suggestions for experiments to test some aspects of this hypothesis, such as evaluating the ability of ribozyme RNA polymerases to generate random ligation products and testing the catalytic activity of linked ribozyme domains.

Highlights

  • It has been proposed previously that complex ribozymes such as the RNA polymerase might have emerged by the random ligation of smaller hairpin-loop structures, which was supported by in silico studies [111]

  • I extended these ideas and argued that the ancient genome might have evolved in a similar way, likely in dry–wet scenarios on early Earth, which have been suggested as plausible sites for liposome formation, the evolution of metabolic protocells, and RNA polymers [5,6]

  • Initial RNA oligo- and polymers may have assembled in such a scenario, assembling into autocatalytic sets contained within liposome containers that form and dissolve repeatedly

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. There are two main hypotheses that can be summarized as ‘RNA-first’ (the RNA world hypothesis), or, more broadly, ‘replicatorfirst’, and ‘metabolism-first’ The former (described in detail below) suggests that the ancestor of the genome arose spontaneously as a self-replicating oligo- or polymer of RNA, and that the metabolism emerged as a consequence of the evolving RNA. The latter hypothesis posits that a metabolism, i.e., a set of chemical reactions and their respective catalysts, within a primordial cell (the protocell) existed and evolved in complexity without any form of genome Compelling arguments for both scenarios have been made in recent decades theoretically as well as by mathematical modeling and experimentation. Formation the protogenome enters newly liposomes (right) There, it can seed both autocatalytic sets as its ribozyme domains are active. Thisribozymes process offrom protometabolism is more efficient than the stochastic co-encapsulation of individual ribozymes from autocatalytic sets A and B

The RNA World
Autocatalytic Sets—Evolution of Metabolism without a Genome
Dividing Liposomes
Evolution of the Genome from RNA-Based Autocatalytic Sets
Protogenome Evolution within the Dry–Wet Cycle Scenario
Emergence
Protogenome Evolution Outside of the Dry–Wet Cycle Scenario
Further Evolution of the Protogenome—En Route to LUCA
Discussion
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