• RNA assembly
• RNA structure
• loop-closing ligation
• origin of life
• prebiotic chemistry

• RNA/chemistry
• RNA/metabolism
• RNA/genetics
• Nucleic Acid Conformation

• 2104708 NSF
• Howard Hughes Medical Institute
• 2325198 NSF
• R01GM145986 NIH HHS
• R01 GM145986 NIGMS NIH HHS
• NSF
• NIH
• Howard Hughes Medical Institute

• molecular evolution
• organisms
• organs
• origin of life
• proto-organs
• reproduction

• MICINN

• RNA archaeology
• RNA virus
• RNase P
• RNase‐III
• UV‐C‐light
• mRNA
• palimpsest
• viral‐quasispecies

• RNA, Viral/genetics
• RNA, Viral/chemistry
• Evolution, Molecular
• RNA Viruses/genetics
• Humans
• Animals
• Archaeology

• PROYECTOS DE I+D+i Ministerio de Ciencia e Innovacion (MICINN)
• PID2020-113888RB-I00 Ministerio de Ciencia e Innovacion (MICINN)
• PID2019-104903RB-I00 Ministerio de Ciencia e Innovacion (MICINN)
• Agencia Estatal de Investigacion (AEI)

• RNA world
• coexistence
• error threshold
• evolutionary biology
• none
• parabolic growth
• template replication

• RNA/genetics
• RNA/metabolism
• Stochastic Processes
• Evolution, Molecular

• TWCF0268 TWCF
• National Research, Development and Innovation Office
• Templeton World Charity Foundation
• Hungarian Academy of Sciences
• Eötvös Loránd University

• Consortial properties
• Early evolution
• Genetic innovation
• Mutation
• RNA networks
• Virus

• Quasispecies

• RNA world
• aminoacylation
• genetic code
• origin of life
• proto-ribosome
• ribosome evolution
• tRNA
• translation

• RNA stem-loop groups
• biocommunication
• excess productivity
• gangs of life
• learning
• memory
• social behavior

• RNA/genetics
• RNA/chemistry
• Nucleic Acid Conformation
• Viruses
• Ribosomes

• RNA stem-loop groups
• biocommunication
• excess productivity
• gangs of life
• learning
• memory
• social behavior

• RNA/genetics
• RNA/chemistry
• Nucleic Acid Conformation
• Viruses
• Ribosomes

• Darwinian evolution
• RNA
• RNA world
• autocatalytic sets
• chemical evolution
• origin of life
• replicase
• ribozyme
• template-based replication

• Isoxazoles
• Origin of Life
• Prebiotic Chemistry
• Proto-RNA
• RNA

• Nucleosides/chemistry
• RNA/chemistry
• Isoxazoles
• Cytidine/chemistry
• Urea/chemistry

• Deutsche Forschungsgemeinschaft
• HORIZON EUROPE European Research Council
• Volkswagen Foundation

• genotype–phenotype map
• modularity
• molecular cooperation
• redundancy
• viral evolution
• viroids

• Adaptation, Physiological
• Biological Evolution
• Evolution, Molecular
• Phenotype
• Selection, Genetic

The RNA world is one of the principal hypotheses to explain the emergence of living systems on the prebiotic Earth. It posits that RNA oligonucleotides acted as both carriers of information as well as catalytic molecules, promoting their own replication. However, it does not explain the origin of the catalytic RNA molecules. How could the transition from a pre-RNA to an RNA world occur? A starting point to answer this question is to analyze the dynamics in sequence space on the lowest level, where mononucleotide and short oligonucleotides come together and collectively evolve into larger molecules. To this end, we study the sequence-dependent self-assembly of polymers from a random initial pool of short building blocks via templated ligation. Templated ligation requires two strands that are hybridized adjacently on a third strand. The thermodynamic stability of such a configuration crucially depends on the sequence context and, therefore, significantly influences the ligation probability. However, the sequence context also has a kinetic effect, since non-complementary nucleotide pairs in the vicinity of the ligation site stall the ligation reaction. These sequence-dependent thermodynamic and kinetic effects are explicitly included in our stochastic model. Using this model, we investigate the system-level dynamics inside a non-equilibrium ‘RNA reactor’ enabling a fast chemical activation of the termini of interacting oligomers. Moreover, the RNA reactor subjects the oligomer pool to periodic temperature changes inducing the reshuffling of the system. The binding stability of strands typically grows with the number of complementary nucleotides forming the hybridization site. While shorter strands unbind spontaneously during the cold phase, larger complexes only disassemble during the temperature peaks. Inside the RNA reactor, strand growth is balanced by cleavage via hydrolysis, such that the oligomer pool eventually reaches a non-equilibrium stationary state characterized by its length and sequence distribution. How do motif-dependent energy and stalling parameters affect the sequence composition of the pool of long strands? As a critical factor for self-enhancing sequence selection, we identify kinetic stalling due to non-complementary base pairs at the ligation site. Kinetic stalling enables cascades of self-amplification that result in a strong reduction of occupied states in sequence space. Moreover, we discuss the significance of the symmetry breaking for the transition from a pre-RNA to an RNA world.

• RNA evolution
• hammerhead ribozyme
• origin of life
• rolling circle mechanism
• satellite RNA
• viroid-like RNA

• Ministerio de Economía y Competitividad of Spain (MINECO)

• RNA ligase
• RNA world
• autocatalytic sets
• early Earth
• genome evolution
• ribozymes

• catalysis
• coacervates
• ligases
• peptides
• ribozymes

• Biocatalysis
• Oligonucleotides/biosynthesis
• Oligonucleotides/chemistry
• Peptides/chemistry
• Peptides/metabolism
• RNA/chemistry
• RNA/metabolism
• RNA, Catalytic/metabolism

• 92772 Volkswagen Foundation
• 364653263 Deutsche Forschungsgemeinschaft
• 802000 European Research Council
• Volkswagen Foundation
• European Research Council
• Deutsche Forschungsgemeinschaft

• Code biology
• Macrocode
• Origin of life
• Progenote.

• Experimental evolution
• Fitness landscape
• Genotype network
• Genotype-phenotype map
• Molecular evolution
• Phenotypic bias

• membership roles
• quasispecies consortia
• virolution
• virus persistence

Viroids are non-coding circular RNA molecules with rod-like or branched structures. They are often ribozymes, characterized by catalytic RNA. They can perform many basic functions of life and may have played a role in evolution since the beginning of life on Earth. They can cleave, join, replicate, and undergo Darwinian evolution. Furthermore, ribozymes are the essential elements for protein synthesis of cellular organisms as parts of ribosomes. Thus, they must have preceded DNA and proteins during evolution. Here, we discuss the current evidence for viroids or viroid-like RNAs as a likely origin of life on Earth. As such, they may also be considered as models for life on other planets or moons in the solar system as well as on exoplanets.

• RNase P
• early earth
• endosymbionts
• exoplanets
• meteorites
• non-coding RNA
• ribozymes

• Animals
• Gene Silencing
• Genetic Complementation Test
• Humans
• Meteoroids
• Nucleic Acid Conformation
• Origin of Life
• Plant Diseases/virology
• RNA Interference
• RNA, Catalytic/genetics
• RNA, Viral/genetics
• Ribosomes/chemistry
• Ribosomes/genetics
• Symbiosis
• Viroids/genetics
• Virus Diseases/metabolism
• Virus Replication

Thresholds are widespread in origin of life scenarios, from the emergence of chirality, to the appearance of vesicles, of autocatalysis, all the way up to Darwinian evolution. Here, we analyze the “error threshold,” which poses a condition for sustaining polymer replication, and generalize the threshold approach to other properties of prebiotic systems. Thresholds provide theoretical predictions, prescribe experimental tests, and integrate interdisciplinary knowledge. The coupling between systems and their environment determines how thresholds can be crossed, leading to different categories of prebiotic transitions. Articulating multiple thresholds reveals evolutionary properties in prebiotic scenarios. Overall, thresholds indicate how to assess, revise, and compare origin of life scenarios.

• Astrobiology
• Astrochemistry
• Biochemistry
• Biological Sciences
• Chemistry
• Evolutionary Biology
• Evolutionary Processes

Abiotic emergence of ordered information stored in the form of RNA is an important unresolved problem concerning the origin of life. A polymer longer than 40–100 nucleotides is necessary to expect a self-replicating activity, but the formation of such a long polymer having a correct nucleotide sequence by random reactions seems statistically unlikely. However, our universe, created by a single inflation event, likely includes more than 10¹⁰⁰ Sun-like stars. If life can emerge at least once in such a large volume, it is not in contradiction with our observations of life on Earth, even if the expected number of abiogenesis events is negligibly small within the observable universe that contains only 10²² stars. Here, a quantitative relation is derived between the minimum RNA length l_min required to be the first biological polymer, and the universe size necessary to expect the formation of such a long and active RNA by randomly adding monomers. It is then shown that an active RNA can indeed be produced somewhere in an inflationary universe, giving a solution to the abiotic polymerization problem. On the other hand, l_min must be shorter than ~20 nucleotides for the abiogenesis probability close to unity on a terrestrial planet, but a self-replicating activity is not expected for such a short RNA. Therefore, if extraterrestrial organisms of a different origin from those on Earth are discovered in the future, it would imply an unknown mechanism at work to polymerize nucleotides much faster than random statistical processes.

• RNA world
• evolution
• multiloops
• self-replication

• Base Composition
• Base Sequence
• Evolution, Molecular
• Mutation
• Nucleic Acid Conformation
• RNA/chemistry
• RNA/genetics
• RNA Folding
• RNA Stability
• Structure-Activity Relationship
• Transcription, Genetic

• NSERC

• Biological information
• Origin of life
• RNA
• RNA sctructure

• Base Sequence
• Codon/genetics
• Models, Molecular
• Nucleic Acid Conformation
• Nucleotide Motifs
• Protein Biosynthesis
• RNA/chemistry
• RNA/genetics
• Thermodynamics
• Transcription, Genetic

• RNA world
• RNase III
• RNase P
• biocommunication
• biosemiotics
• quasispecies

Viroids are small, non-coding, circular RNA molecules that infect plants. Different hypotheses for their evolutionary origin have been put forward, such as an early emergence in a precellular RNA World or several de novo independent evolutionary origins in plants. Here, we discuss the plausibility of de novo emergence of viroid-like replicons by giving theoretical support to the likelihood of different steps along a parsimonious evolutionary pathway. While Avsunviroidae-like structures are relatively easy to obtain through evolution of a population of random RNA sequences of fixed length, rod-like structures typical of Pospiviroidae are difficult to fix. Using different quantitative approaches, we evaluated the likelihood that RNA sequences fold into a rod-like structure and bear specific sequence motifs facilitating interactions with other molecules, e.g., RNA polymerases, RNases, and ligases. By means of numerical simulations, we show that circular RNA replicons analogous to Pospiviroidae emerge if evolution is seeded with minimal circular RNAs that grow through the gradual addition of nucleotides. Further, these rod-like replicons often maintain their structure if independent functional modules are acquired that impose selective constraints. The evolutionary scenario we propose here is consistent with the structural and biochemical properties of viroids described to date.

• RNA secondary structure
• computational simulations
• modular evolution
• population dynamics
• simple replicators
• structure enumeration
• viroid

• Evolution, Molecular
• Nucleic Acid Conformation
• RNA, Circular/chemistry
• RNA, Circular/genetics
• RNA, Viral/chemistry
• RNA, Viral/genetics
• Replicon
• Viral Proteins/genetics
• Viroids/chemistry
• Viroids/classification
• Viroids/genetics
• Viroids/physiology
• Virus Replication

• RNA
• oligomers
• origins of life
• recombination
• ribozymes

• Base Pairing
• Base Sequence
• Genetic Variation
• Models, Chemical
• Oligoribonucleotides/chemical synthesis
• Oligoribonucleotides/chemistry
• Oligoribonucleotides/genetics
• Origin of Life
• RNA/chemical synthesis
• RNA/chemistry
• RNA/genetics
• Recombination, Genetic

• John Templeton Foundation

• RNA networks
• cells
• communication
• disease
• genomic parasites
• quasispecies
• viruses

• RNA world
• alanine
• genetic code
• tmRNA
• trans-translation

Central to the “RNA world” hypothesis of the origin of life is the emergence of an RNA catalyst capable of RNA replication. However, possible replicase ribozymes are quite complex and were likely predated by simpler non-enzymatic replication reactions. The templated polymerisation of phosphorimidazolide (Imp) activated ribonucleotides currently appears as the most tractable route to both generate and replicate short RNA oligomer pools from which a replicase could emerge. Herein we demonstrate the rapid assembly of complex ribozymes from such Imp-activated RNA fragment pools. Specifically, we show assembly of a newly selected minimal RNA polymerase ribozyme variant (150 nt) by RNA templated ligation of 5’-2-methylimidazole-activated RNA oligomers <30 nucleotides long. Our results provide support for the possibility that complex RNA structures could have emerged from pools of activated RNA oligomers and outlines a path for the transition from non-enzymatic/chemical to enzymatic RNA replication.

• RNA
• nucleic acids
• origin of life
• phosphorimidazolide
• ribozymes
• templated ligation

• Adsorption
• Catalysis
• Earth, Planet
• Hot Temperature
• Minerals/chemistry
• Origin of Life
• RNA/chemistry
• Surface Properties

• 80NSSC17K0296 Intramural NASA

The feasibility of self-assembly of a translation system from prebiotic random RNA chains is a question that is central to the ability to conceive life emerging by natural processes. The spontaneous materialization of a translation system would have required the autonomous formation of proto-transfer RNA (tRNA) and proto-ribosome molecules that are indispensable for translating an RNA chain into a polypeptide. Currently, the vestiges of a non-coded proto-ribosome, which could have only catalyzed the formation of a peptide bond between random amino acids, is consensually localized in the region encircling the peptidyl transferase center of the ribosomal large subunit. The work presented here suggests, based on high resolution structures of ribosomes complexed with messenger RNA (mRNA) and tRNAs, that three types of L-shaped RNA building blocks derived from the modern ribosome, alongside with an L-shaped proto-tRNA, each composed of about 70-mer, could have randomly occurred in the prebiotic world and combined to form a simple translation system. The model of the initial coded proto-ribosome, which includes the active sites of both ribosomal subunits, together with a bridging element, incorporates less than 6% of the current prokaryotic rRNA, yet it integrates all of the ribosomal components that are vital for synthesizing the earliest coded polypeptides.

• evolution
• origin of life
• proto-ribosome
• ribosome
• tRNA
• translation

Recombination, the exchange of information between different genetic polymer strands, is of fundamental importance in biology for genome maintenance and genetic diversification and is mediated by dedicated recombinase enzymes. Here, we describe an innate capacity for non-enzymatic recombination (and ligation) in random-sequence genetic oligomer pools. Specifically, we examine random and semi-random eicosamer (N₂₀) pools of RNA, DNA and the unnatural genetic polymers ANA (arabino-), HNA (hexitol-) and AtNA (altritol-nucleic acids). While DNA, ANA and HNA pools proved inert, RNA (and to a lesser extent AtNA) pools displayed diverse modes of spontaneous intermolecular recombination, connecting recombination mechanistically to the vicinal ring cis-diol configuration shared by RNA and AtNA. Thus, the chemical constitution that renders both susceptible to hydrolysis emerges as the fundamental determinant of an innate capacity for recombination, which is shown to promote a concomitant increase in compositional, informational and structural pool complexity and hence evolutionary potential.

• RNA
• biochemistry
• chemical biology
• ligation
• non-enzymatic
• none
• nucleic acids
• origin of life
• recombination

• Benzonase
• Dynamic combinatorial chemistry
• Origin of life
• RNA World
• Sequence space
• T4 RNA ligase

• Natural Genetic Content Operators
• RNA Networks
• genetic identities
• infectious agents
• regulatory RNAs

In recent years, an extension of the Darwinian framework is being considered for the study of prebiotic chemical evolution, shifting the attention from homogeneous populations of naked molecular species to populations of heterogeneous, compartmentalized and functionally integrated assemblies of molecules. Several implications of this shift of perspective are analysed in this critical review, both in terms of the individual units, which require an adequate characterization as self-maintaining systems with an internal organization, and also in relation to their collective and long-term evolutionary dynamics, based on competition, collaboration and selection processes among those complex individuals. On these lines, a concrete proposal for the set of molecular control mechanisms that must be coupled to bring about autonomous functional systems, at the interface between chemistry and biology, is provided.

• autonomous functional systems
• chemical evolution
• natural selection
• origins of life
• prebiotic systems chemistry

The synthesis of a 5′-boronoribonucleotidic phosphoramidite building block has been achieved and incorporated at the 5′ extremities of RNA sequences for the templated assembly of RNA shortmers.

• evolution of sex
• fitness landscape
• in vitro recombination
• laboratory directed evolution
• origin of life

• chemical evolution
• left-skewed right-weighted probability distribution
• origin of life
• stochastic dynamical model
• thermochemical and pH oscillator

• Molecular dynamics
• Non-enzymatic RNA ligation
• Origin of life
• RNA world

• catalytic RNA
• complexity
• molecular trade-off
• origin of life

• National Science Foundation
• National Research Foundation
• University of the Witwatersrand, Johannesburg
• National Aeronautics and Space Administration

• DNA
• RNA
• RNA group identities
• RNA stem loops
• repetitive sequences

• clay
• in vitro evolution
• mineral
• origin of life
• ribozyme

• Aluminum Silicates
• Clay
• Minerals/chemistry
• RNA, Catalytic/chemistry
• Surface Properties

• Physical knots
• RNA knots
• RNA structure

• NMR spectroscopy
• Non-uniform sampling
• Proteins
• RNA
• Sparse sampling

• Humans
• Nuclear Magnetic Resonance, Biomolecular/methods
• Proteins/chemistry
• RNA/chemistry
• Solutions

• Four-dimensional NMR
• HCP
• Non-uniform sampling
• RNA resonance assignment
• Selective pulses

• Carbon Isotopes/chemistry
• Nuclear Magnetic Resonance, Biomolecular/methods
• Nucleic Acid Conformation
• RNA/chemistry