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Schematic representation of population structures in models of prebiotic replicators. (A) In a well-mixed model, no population structure is assumed, hence free movement of molecules is allowed. (B) In the case of surface-bound molecules, the replicators have a limited number of immediate neighbors and their translocation (dispersal, diffusion) is limited. (C) The stochastic corrector model assumes that replicators multiply inside vesicles with a membrane boundary, and successful replication of the community will accelerate vesicle growth and division, which defines the fitness of these protocells.
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The RNA world hypothesis of the origin of life, in which RNA emerged as both enzyme and information carrier, is receiving solid experimental support. The prebiotic synthesis of biomolecules, the catalytic aid offered by mineral surfaces, and the vast enzymatic repertoire of ribozymes are only pieces of the origin of life puzzle; the full picture ca...
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... besides their favorable kinetic and thermodynamic effects on an unfolding chemical network, 140,141 have an important role in provid- ing population structures in which evolution is known to proceed differently from its course in a well-mixed flow reactor (cf. Fig. 3). A potential interaction network was explored by the metaboli- cally coupled replicator system (MCRS) 142 (see Fig. 2C). Replicators in the MCRS interact with each other indirectly; namely, every replicator catalyzes only one reaction in a hypothetical metabolic re- action network carrying out monomer production, but all of the ...
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... replicator model, MRM), however, replicators stably coexist in most parts of the parameter space. 142,143 Local interactions and limited mixing of replicators in the spatially explicit model ensure that the metabolic network is more likely to be complete in the neighborhood of rare replicators than in the vicinity of dom- inant replicators (see Fig. 3B), thus providing a control over the dominant species (advantage of rarity). 142,143 The MCRS has a double advantage against par- asites over the hypercycle. Because the main cou- pling is indirect via metabolism, the short-circuit parasite (in contrast to the hypercycle case) has no meaning (see Fig. 2D). Moreover, harmful effects of ...
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... cells, and thus selection can act on this variation. It was shown that the stochastic nature of the daughter cell com- position in fact facilitates coexistence, as, by chance, daughter cells could inherit a balanced gene set even if the parental cell had a suboptimal distribution of genes. 171 Hence, the name of the model: stochastic corrector (Fig. 3C). This process protects the pop- ulation from extinction and results in evolutionary dynamics yielding a stable quasispecies at the level of compartments. 172 The SCM is inherently stable against parasites. It has the ability to select against inferior and for superior mutants. [173][174][175][176] The cells of the SCM are individuals ...
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The RNA world hypothesis describes a stage in the early evolution of life in which catalytic RNAs mediated the replication of RNA world organisms. One challenge to this hypothesis is that most existing ribozymes are much longer than what may be expected to originate from prebiotically plausible methods, or from the polymerization by currently exist...
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... Early RNA genes could have been very short, reaching a maximum length of 50 to 100 nt, with most probably configured into mini-helixes whose strands must are stable and therefore equivalent to each other in topology and chemical composition [5][6][7]10,[13][14][15][16][17][18][19]. These probably functioned as proto-tRNAs [20][21][22][23]. ...
... RNA could then have polymerised and randomly generated short ribonucleic chains in which the RNY pa ern gradually began to prevail, as if it was a quasi-species [6,58] that evolved through cooperative interaction via cyclic coupling, i.e., hypercycles. Those RNA short sequences and their limited diversity supported prebiotic, autocatalytic reproduction by means of hypercycles [ 5,10,[15][16][17][18]21]. Lastly, it is safe to assume that the Ur-RNA proposed here, encoded by the PGC, emerged before the so-called "First Universal Common Ancestor" (FUCA), because the PTC cannot be found encoded by RNY triplets [69,70]. ...
... RNA could then have polymerised and randomly generated short ribonucleic chains in which the RNY pattern gradually began to prevail, as if it was a quasi-species [6,58] that evolved through cooperative interaction via cyclic coupling, i.e., hypercycles. Those RNA short sequences and their limited diversity supported prebiotic, autocatalytic reproduction by means of hypercycles [ 5,10,[15][16][17][18]21]. Lastly, it is safe to assume that the Ur-RNA proposed here, encoded by the PGC, emerged before the so-called "First Universal Common Ancestor" (FUCA), because the PTC cannot be found encoded by RNY triplets [69,70]. ...
It is widely accepted that the earliest RNA molecules were folded into hairpins or mini-helixes. Herein, we depict the 2D and 3D conformations of those earliest RNA molecules with only RNY triplets, which Eigen proposed as the primeval genetic code. We selected 26 species (13 bacteria and 13 archaea). We found that the free energy of RNY hairpins was consistently lower than that of their corresponding shuffled controls. We found traces of the three ribosomal RNAs (16S, 23S, and 5S), tRNAs, 6S RNA, and the RNA moieties of RNase P and the signal recognition particle. Nevertheless, at this stage of evolution there was no genetic code (as seen in the absence of the peptidyl transferase centre and any vestiges of the anti-Shine-Dalgarno sequence). Interestingly, we detected the anticodons of both glycine (GCC) and threonine (GGU) in the hairpins of proto-tRNA.
... In non-coding RNAs, even single-nucleotide variations (SNVs) can induce dynamic alterations in the RNA's secondary structure, potentially resulting in functional impairment [10]. Nevertheless, certain mutational flexibility is granted through sequence covariation, enabling multiple nucleotide alterations while preserving the functional structure [11]. Hence, RNA sequences play a pivotal role in bridging the gap between structure and function. ...
The function of RNAs is determined by their structure. However, studying the relationship between RNA structure and function often requires altering RNA sequences to modify the structures, which leads to the neglect of the importance of RNA sequences themselves. In our research, we utilized potato spindle tuber viroid (PSTVd), a circular-form non-coding infectious RNA, as a model with which to investigate the role of a specific rod-like structure in RNA function. By generating linear RNA transcripts with different start sites, we established 12 PSTVd forms with different secondary structures while maintaining the same sequence. The RNA secondary structures were predicted using the mfold tool and validated through native PAGE gel electrophoresis after in vitro RNA folding. Analysis using plant infection assays revealed that the formation of a correct rod-like structure is crucial for the successful infection of PSTVd. Interestingly, the inability of PSTVd forms with non-rod-like structures to infect plants could be partially compensated by increasing the amount of linear viroid RNA transcripts, suggesting the existence of additional RNA secondary structures, such as the correct rod-like structure, alongside the dominant structure in the RNA inoculum of these forms. Our study demonstrates the critical role of RNA secondary structures in determining the function of infectious RNAs.
... The ribonucleic acid (RNA) world hypothesis is widely recognized as one of the 'origin of life' (1)(2)(3)(4)(5). In the RNA world, RNA had two functions: information storage and catalytic activities. ...
How the ribonucleic acid (RNA) world transited to the deoxyribonucleic acid (DNA) world has remained controversial in evolutionary biology. At a certain time point in the transition from the RNA world to the DNA world, ‘RNA replicons’, in which RNAs produce proteins to replicate their coding RNA, and ‘DNA replicons’, in which DNAs produce RNA to synthesize proteins that replicate their coding DNA, can be assumed to coexist. The coexistent state of RNA replicons and DNA replicons is desired for experimental approaches to determine how the DNA world overtook the RNA world. We constructed a mini-RNA replicon in Escherichia coli. This mini-RNA replicon encoded the β subunit, one of the subunits of the Qβ replicase derived from the positive-sense single-stranded Qβ RNA phage and is replicated by the replicase in E. coli. To maintain the mini-RNA replicon persistently in E. coli cells, we employed a system of α complementation of LacZ that was dependent on the Qβ replicase, allowing the cells carrying the RNA replicon to grow in the lactose minimal medium selectively. The coexistent state of the mini-RNA replicon and DNA replicon (E. coli genome) was successively synthesized. The coexistent state can be used as a starting system to experimentally demonstrate the transition from the RNA–protein world to the DNA world, which will contribute to progress in the research field of the origin of life.
... The discovery of catalytic RNAs and the fact that the ribosome itself is a ribozyme has added strong supporting evidence to this concept [12,13]. However, there is still an unresolved problem concerning the emergence of self-replicating RNA-only polymerase ribozyme (RNA replicase) from prebiotic conditions [14]. To complicate matters further, with the evolution of proteins, the catalytic properties of RNA were no longer needed and the ancestral replicases were entirely replaced by more efficient proteinaceous counterparts-namely, protein polymerase enzymes [15,16]. ...
The origin of life remains one of the major scientific questions in modern biology. Among many hypotheses aiming to explain how life on Earth started, RNA world is probably the most extensively studied. It assumes that, in the very beginning, RNA molecules served as both enzymes and as genetic information carriers. However, even if this is true, there are many questions that still need to be answered—for example, whether the population of such molecules could achieve stability and retain genetic information for many generations, which is necessary in order for evolution to start. In this paper, we try to answer this question based on the parasite–replicase model (RP model), which divides RNA molecules into enzymes (RNA replicases) capable of catalyzing replication and parasites that do not possess replicase activity but can be replicated by RNA replicases. We describe the aforementioned system using partial differential equations and, based on the analysis of the simulation, surmise general rules governing its evolution. We also compare this approach with one where the RP system is modeled and implemented using a multi-agent modeling technique. We show that approaching the description and analysis of the RP system from different perspectives (microscopic represented by MAS and macroscopic depicted by PDE) provides consistent results. Therefore, applying MAS does not lead to erroneous results and allows us to study more complex situations where many cases are concerned, which would not be possible through the PDE model.
... The closest to an experimentally verified self-replicating RNA system has been a set of two RNA ligase ribozymes that catalyze each other's formation (a simple autocatalytic set), which however requires complex preformed RNA building blocks [48]. Moreover, if the first replicator was a self-replicating RdRp ribozyme, its spontaneous emergence is highly unlikely given that it would consist of about 200 nucleotides [35,49]. In addition, a spontaneously emerging RdRp is likely to be error-prone and therefore unlikely to enable stable self-replication [35,46]. ...
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.
... Theoretical analysis has been conducted into RNA origins. Attention has been drawn to an evolving population of dynamical systems and how dynamics affect the error threshold of early replicators and possibly towards compartmentalization conveying hypercycles [43]. String-replicator dynamics have been studied and properties suggested to be necessary to RNA origins, including the ability to operate a functional genetic communication system and ecological and evolutionary stability [44][45][46]. ...
Can a replicase be found in the vast sequence space by random drift? We partially answer this question through a proof-of-concept study of the times of occurrence (hitting times) of some critical events in the origins of life for low-dimensional RNA sequences using a mathematical model and stochastic simulation studies from Python software. We parameterize fitness and similarity landscapes for polymerases and study a replicating population of sequences (randomly) participating in template-directed polymerization. Under the ansatz of localization where sequence proximity correlates with spatial proximity of sequences, we find that, for a replicating population of sequences, the hitting and establishment of a high-fidelity replicator depends critically on the polymerase fitness and sequence (spatial) similarity landscapes and on sequence dimension. Probability of hitting is dominated by landscape curvature, whereas hitting time is dominated by sequence dimension. Surface chemistries, compartmentalization, and decay increase hitting times. Compartmentalization by vesicles reveals a trade-off between vesicle formation rate and replicative mass, suggesting that compartmentalization is necessary to ensure sufficient concentration of precursors. Metabolism is thought to be necessary to replication by supplying precursors of nucleobase synthesis. We suggest that the dynamics of the search for a high-fidelity replicase evolved mostly during the final period and, upon hitting, would have been followed by genomic adaptation of genes and to compartmentalization and metabolism, effecting degree-of-freedom gains of replication channel control over domain and state to ensure the fidelity and safe operations of the primordial genetic communication system of life.
... Mutants displaying higher or lower fidelity than their parental wild-type viruses (Section 2) are often attenuated, show defects in replication, and are not found as dominant genomes in mutant spectra evolving in nature. There are biochemical and evolutionary arguments that favor the view that primitive replicons displayed high error rates [67,68]. It is tempting to propose that error-prone replication is not a biological novelty of the cellular-viral world. ...
The error rate displayed during template copying to produce viral RNA progeny is a biologically relevant parameter of the replication complexes of viruses. It has consequences for virus–host interactions, and it represents the first step in the diversification of viruses in nature. Measurements during infections and with purified viral polymerases indicate that mutation rates for RNA viruses are in the range of 10−3 to 10−6 copying errors per nucleotide incorporated into the nascent RNA product. Although viruses are thought to exploit high error rates for adaptation to changing environments, some of them possess misincorporation correcting activities. One of them is a proofreading-repair 3′ to 5′ exonuclease present in coronaviruses that may decrease the error rate during replication. Here we review experimental evidence and models of information maintenance that explain why elevated mutation rates have been preserved during the evolution of RNA (and some DNA) viruses. The models also offer an interpretation of why error correction mechanisms have evolved to maintain the stability of genetic information carried out by large viral RNA genomes such as the coronaviruses
... The RNA world [1][2][3] is an era during the origin of life when RNA played the role of both information storage molecule and enzymes. Ribozymes are the embodiments of this last function. ...
The RNA world is an era during the origin of life when RNA played the role of both information storage molecule and enzymes. RNA, in its dual roles as enzymes and information, regulates the processes of the ribocell. Thus, ribozymes were truly at the hearth of what it meant to be alive. In modern cells, metabolism is run mostly by peptide enzymes, and information is stored in DNA, but RNAs shuttle information between DNA and peptides, and they have a significant role in the regulation of cellular processes. The chapter considers the RNA world to last till DNA takes over as the main information storage molecule. The most important enzymatic function of a ribocell is the replication of the genetic material. It requires at least one enzyme, the RNA‐dependent RNA polymerase. A smaller set of RNAs can also directly control translation, inhibiting or facilitating the production of enzymes from the chromosome.
... This focus suppresses discussion of numerous weaknesses of the RNA World hypothesis itself and ignores considerable recent experimental evidence consistent with a more probable alternative scenario. The RNA World assumption is widely held (38)(39)(40)(41)(42), but it rests almost entirely on facile extrapolation from the fact that proteins cannot transmit linear sequence information from generation to generation, whereas RNA can catalyze a limited repertoire of hydrolytic and transesterification reactions in cells (43). The assumption has little actual experimental support beyond selection of catalytic aptamers from combinatorial RNA libraries. ...
Codon-dependent translation underlies genetics and phylogenetic inferences, but its origins pose two challenges. Prevailing narratives cannot account for the fact that aminoacyl-tRNA synthetases (aaRSs), which translate the genetic code, must collectively enforce the rules used to assemble themselves. Nor can they explain how specific assignments arose from rudimentary differentiation between ancestral aaRSs and corresponding transfer RNAs (tRNAs). Experimental deconstruction of the two aaRS superfamilies created new experimental tools with which to analyze the emergence of the code. Amino acid and tRNA substrate recognition are linked to phase transfer free energies of amino acids and arise largely from aaRS class-specific differences in secondary structure. Sensitivity to protein folding rules endowed ancestral aaRS–tRNA pairs with the feedback necessary to rapidly compare alternative genetic codes and coding sequences. These and other experimental data suggest that the aaRS bidirectional genetic ancestry stabilized the differentiation and interdependence required to initiate and elaborate the genetic coding table.
Expected final online publication date for the Annual Review of Biochemistry, Volume 90 is June 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... The closest to an experimentally verified self-replicating RNA system has been a set of two RNA ligase ribozymes that catalyze each other's formation (a simple autocatalytic set), which however requires complex preformed RNA building blocks [44]. Moreover, if the first replicator was a self-replicating RdRp ribozyme, its spontaneous emergence is highly unlikely given that it would consists of about 200 nucleotides [31,45]. In addition, a spontaneously emerging RdRp is likely to be error-prone and therefore unlikely to enable stable self-replication [31,42]. ...
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.
