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Balazs Konnyű - One of the best experts on this subject based on the ideXlab platform.
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ecology and evolution in the rna world dynamics and stability of prebiotic Replicator systems
Life, 2017Co-Authors: András Szilágyi, Istvan Zachar, Istvan Scheuring, Adam Kun, Balazs KonnyűAbstract:As of today, the most credible scientific paradigm pertaining to the origin of life on Earth is undoubtedly the RNA World scenario. It is built on the assumption that catalytically active Replicators (most probably RNA-like macromolecules) may have been responsible for booting up life almost four billion years ago. The many different incarnations of nucleotide sequence (string) Replicator models proposed recently are all attempts to explain on this basis how the genetic information transfer and the functional diversity of prebiotic Replicator systems may have emerged, persisted and evolved into the first living cell. We have postulated three necessary conditions for an RNA World model system to be a dynamically feasible representation of prebiotic chemical evolution: (1) it must maintain and transfer a sufficient diversity of information reliably and indefinitely, (2) it must be ecologically stable and (3) it must be evolutionarily stable. In this review, we discuss the best-known prebiotic scenarios and the corresponding models of string-Replicator dynamics and assess them against these criteria. We suggest that the most popular of prebiotic Replicator systems, the hypercycle, is probably the worst performer in almost all of these respects, whereas a few other model concepts (parabolic Replicator, open chaotic flows, stochastic corrector, metabolically coupled Replicator system) are promising candidates for development into coherent models that may become experimentally accessible in the future.
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In silico ribozyme evolution in a metabolically coupled RNA population
Biology Direct, 2015Co-Authors: Balazs Konnyű, András Szilágyi, Tamas CzaranAbstract:Background The RNA World hypothesis offers a plausible bridge from no-life to life on prebiotic Earth, by assuming that RNA, the only known molecule type capable of playing genetic and catalytic roles at the same time, could have been the first evolvable entity on the evolutionary path to the first living cell. We have developed the Metabolically Coupled Replicator System (MCRS), a spatially explicit simulation modelling approach to prebiotic RNA-World evolution on mineral surfaces, in which we incorporate the most important experimental facts and theoretical considerations to comply with recent knowledge on RNA and prebiotic evolution. In this paper the MCRS model framework has been extended in order to investigate the dynamical and evolutionary consequences of adding an important physico-chemical detail, namely explicit Replicator structure – nucleotide sequence and 2D folding calculated from thermodynamical criteria – and their possible mutational changes, to the assumptions of a previously less detailed toy model. Results For each mutable nucleotide sequence the corresponding 2D folded structure with minimum free energy is calculated, which in turn is used to determine the fitness components (degradation rate, replicability and metabolic enzyme activity) of the Replicator. We show that the community of such Replicators providing the monomer supply for their own replication by evolving metabolic enzyme activities features an improved propensity for stable coexistence and structural adaptation. These evolutionary advantages are due to the emergent uniformity of metabolic Replicator fitnesses imposed on the community by local group selection and attained through Replicator trait convergence, i.e., the tendency of Replicator lengths, ribozyme activities and population sizes to become similar between the coevolving Replicator species that are otherwise both structurally and functionally different. Conclusions In the most general terms it is the surprisingly high extra viability of the metabolic Replicator system that the present model adds to the MCRS concept of the origin of life. Surface-bound, metabolically coupled RNA Replicators tend to evolve different, enzymatically active sites within thermodynamically stable secondary structures, and the system as a whole evolves towards the robust coexistence of a complete set of such ribozymes driving the metabolism producing monomers for their own replication. Reviewers This article was reviewed by Gáspár Jékely, Anthony Poole and Armen Mulkidjanian
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spatial aspects of prebiotic Replicator coexistence and community stability in a surface bound rna world model
BMC Evolutionary Biology, 2013Co-Authors: Balazs Konnyű, Tamas CzaranAbstract:The coexistence of macromolecular Replicators and thus the stability of presumed prebiotic Replicator communities have been shown to critically depend on spatially constrained catalytic cooperation among RNA-like modular Replicators. The necessary spatial constraints might have been supplied by mineral surfaces initially, preceding the more effective compartmentalization in membrane vesicles which must have been a later development of chemical evolution. Using our surface-bound RNA world model – the Metabolic Replicator Model (MRM) platform – we show that the mobilities on the mineral substrate surface of both the macromolecular Replicators and the small molecules of metabolites they produce catalytically are the key factors determining the stable persistence of an evolvable metabolic Replicator community. The effects of Replicator mobility and metabolite diffusion on different aspects of Replicator coexistence in MRM are determined, including the maximum attainable size of the metabolic Replicator system and its resistance to the invasion of parasitic Replicators. We suggest a chemically plausible hypothetical scenario for the evolution of the first protocell starting from the surface-bound MRM system.
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The evolution of enzyme specificity in the metabolic Replicator model of prebiotic evolution.
PloS one, 2011Co-Authors: Balazs Konnyű, Tamas CzaranAbstract:The chemical machinery of life must have been catalytic from the outset. Models of the chemical origins have attempted to explain the ecological mechanisms maintaining a minimum necessary diversity of prebiotic Replicator enzymes, but little attention has been paid so far to the evolutionary initiation of that diversity. We propose a possible first step in this direction: based on our previous model of a surface-bound metabolic Replicator system we try to explain how the adaptive specialization of enzymatic Replicator populations might have led to more diverse and more efficient communities of cooperating Replicators with two different enzyme activities. The key assumptions of the model are that mutations in the Replicator population can lead towards a) both of the two different enzyme specificities in separate Replicators: efficient “specialists” or b) a “generalist” Replicator type with both enzyme specificities working at less efficiency, or c) a fast-replicating, non-enzymatic “parasite”. We show that under realistic trade-off constraints on the phenotypic effects of these mutations the evolved Replicator community will be usually composed of both types of specialists and of a limited abundance of parasites, provided that the Replicators can slowly migrate on the mineral surface. It is only at very weak trade-offs that generalists take over in a phase-transition-like manner. The parasites do not seriously harm the system but can freely mutate, therefore they can be considered as pre-adaptations to later, useful functions that the metabolic system can adopt to increase its own fitness.
Paulien Hogeweg - One of the best experts on this subject based on the ideXlab platform.
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evolutionary dynamics of rna like Replicator systems a bioinformatic approach to the origin of life
Physics of Life Reviews, 2012Co-Authors: Nobuto Takeuchi, Paulien HogewegAbstract:We review computational studies on prebiotic evolution, focusing on informatic processes in RNA-like Replicator systems. In particular, we consider the following processes: the maintenance of information by Replicators with and without interactions, the acquisition of information by Replicators having a complex genotype-phenotype map, the generation of information by Replicators having a complex genotype-phenotype-interaction map, and the storage of information by Replicators serving as dedicated templates. Focusing on these informatic aspects, we review studies on quasi-species, error threshold, RNA-folding genotype-phenotype map, hypercycle, multilevel selection (including spatial self-organization, classical group selection, and compartmentalization), and the origin of DNA-like Replicators. In conclusion, we pose a future question for theoretical studies on the origin of life.
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on the origin of dna genomes evolution of the division of labor between template and catalyst in model Replicator systems
PLOS Computational Biology, 2011Co-Authors: Nobuto Takeuchi, Paulien Hogeweg, Eugene V KooninAbstract:The division of labor between template and catalyst is a fundamental property of all living systems: DNA stores genetic information whereas proteins function as catalysts. The RNA world hypothesis, however, posits that, at the earlier stages of evolution, RNA acted as both template and catalyst. Why would such division of labor evolve in the RNA world? We investigated the evolution of DNA-like molecules, i.e. molecules that can function only as template, in minimal computational models of RNA Replicator systems. In the models, RNA can function as both template-directed polymerase and template, whereas DNA can function only as template. Two classes of models were explored. In the surface models, Replicators are attached to surfaces with finite diffusion. In the compartment models, Replicators are compartmentalized by vesicle-like boundaries. Both models displayed the evolution of DNA and the ensuing division of labor between templates and catalysts. In the surface model, DNA provides the advantage of greater resistance against parasitic templates. However, this advantage is at least partially offset by the disadvantage of slower multiplication due to the increased complexity of the replication cycle. In the compartment model, DNA can significantly delay the intra-compartment evolution of RNA towards catalytic deterioration. These results are explained in terms of the trade-off between template and catalyst that is inherent in RNA-only replication cycles: DNA releases RNA from this trade-off by making it unnecessary for RNA to serve as template and so rendering the system more resistant against evolving parasitism. Our analysis of these simple models suggests that the lack of catalytic activity in DNA by itself can generate a sufficient selective advantage for RNA Replicator systems to produce DNA. Given the widespread notion that DNA evolved owing to its superior chemical properties as a template, this study offers a novel insight into the evolutionary origin of DNA.
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The evolution of strand preference in simulated RNA Replicators with strand displacement: Implications for the origin of transcription
Biology direct, 2008Co-Authors: Nobuto Takeuchi, Laura Salazar, Anthony M. Poole, Paulien HogewegAbstract:Background: The simplest conceivable example of evolving systems is RNA molecules that can replicate themselves. Since replication produces a new RNA strand complementary to a template, all templates would eventually become double-stranded and, hence, become unavailable for replication. Thus the problem of how to separate the two strands is considered a major issue for the early evolution of self-replicating RNA. One biologically plausible way to copy a doublestranded RNA is to displace a preexisting strand by a newly synthesized strand. Such copying can in principle be initiated from either the (+) or (-) strand of a double-stranded RNA. Assuming that only one of them, say (+), can act as replicase when single-stranded, strand displacement produces a new replicase if the (-) strand is the template. If, however, the (+) strand is the template, it produces a new template (but no replicase). Modern transcription exhibits extreme strand preference wherein anti-sense strands are always the template. Likewise, replication by strand displacement seems optimal if it also exhibits extreme strand preference wherein (-) strands are always the template, favoring replicase production. Here we investigate whether such strand preference can evolve in a simple RNA Replicator system with strand displacement. Results: We first studied a simple mathematical model of the Replicator dynamics. Our results indicated that if the system is well-mixed, there is no selective force acting upon strand preference per se. Next, we studied an individual-based simulation model to investigate the evolution of strand preference under finite diffusion. Interestingly, the results showed that selective forces “emerge” because of finite diffusion. Strikingly, the direction of the strand preference that evolves [i.e. (+) or (-) strand excess] is a complex non-monotonic function of the diffusion intensity. The mechanism underlying this behavior is elucidated. Furthermore, a speciation-like phenomenon is observed under certain conditions: two extreme replication strategies, namely replicase producers and template producers, emerge and coexist among competing Replicators.
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The Role of Complex Formation and Deleterious Mutations for the Stability of RNA-Like Replicator Systems
Journal of Molecular Evolution, 2007Co-Authors: Nobuto Takeuchi, Paulien HogewegAbstract:In the RNA world hypothesis, RNA(-like) self-Replicators are suggested as the central player of prebiotic evolution. However, there is a serious problem in the evolution of complexity in such Replicators, i.e., the problem of parasites. Parasites, which are replicated by catalytic Replicators (catalysts), but do not replicate the others, can destroy a whole Replicator system by exploitation. Recently, a theoretical study underlined complex formation between Replicators—an often neglected but realistic process—as a stabilizing factor in a Replicator system by demonstrating that complex formation can shift the viable range of diffusion intensity to higher values. In the current study, we extend the previous study of complex formation. Firstly, by investigating a well-mixed Replicator system, we establish that complex formation gives parasites an implicit advantage over catalysts, which makes the system significantly more vulnerable to parasites. Secondly, by investigating a spatially extended Replicator system, we show that the formation of traveling wave patterns plays a crucial role in the stability of the system against parasites, and that because of this the effect of complex formation is not straightforward; i.e., whether complex formation stabilizes or destabilizes the spatial system is a complex function of other parameters. We give a detailed analysis of the spatial system by considering the pattern dynamics of waves. Furthermore, we investigate the effect of deleterious mutations. Surprisingly, high mutation rates can weaken the exploitation of the catalyst by the parasite.
Tamas Czaran - One of the best experts on this subject based on the ideXlab platform.
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From self-replication to Replicator systems en route to de novo life
Nature Reviews Chemistry, 2020Co-Authors: Paul Adamski, Tamas Czaran, András Szilágyi, Eörs Szathmáry, Adam Kun, Marcel Eleveld, Ankush Sood, Sijbren OttoAbstract:The process by which chemistry can give rise to biology remains one of the biggest mysteries in contemporary science. The de novo synthesis and origin of life both require the functional integration of three key characteristics — replication, metabolism and compartmentalization — into a system that is maintained out of equilibrium and is capable of open-ended Darwinian evolution. This Review takes systems of self-replicating molecules as starting points and describes the steps necessary to integrate additional characteristics of life. We analyse how far experimental self-Replicators have come in terms of Darwinian evolution. We also cover models of Replicator communities that attempt to solve Eigen’s paradox, whereby accurate replication needs complex machinery yet obtaining such complex self-Replicators through evolution requires accurate replication. Successful models rely on a collective metabolism and a way of (transient) compartmentalization, suggesting that the invention and integration of these two characteristics is driven by evolution. Despite our growing knowledge, there remain numerous key challenges that may be addressed by a combined theoretical and experimental approach. Self-replicating systems play a central role in the emergence of life. This Review describes the features that self-replicating systems need to acquire to transition from chemistry to biology and surveys the progress made in theoretical and experimental approaches.
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In silico ribozyme evolution in a metabolically coupled RNA population
Biology Direct, 2015Co-Authors: Balazs Konnyű, András Szilágyi, Tamas CzaranAbstract:Background The RNA World hypothesis offers a plausible bridge from no-life to life on prebiotic Earth, by assuming that RNA, the only known molecule type capable of playing genetic and catalytic roles at the same time, could have been the first evolvable entity on the evolutionary path to the first living cell. We have developed the Metabolically Coupled Replicator System (MCRS), a spatially explicit simulation modelling approach to prebiotic RNA-World evolution on mineral surfaces, in which we incorporate the most important experimental facts and theoretical considerations to comply with recent knowledge on RNA and prebiotic evolution. In this paper the MCRS model framework has been extended in order to investigate the dynamical and evolutionary consequences of adding an important physico-chemical detail, namely explicit Replicator structure – nucleotide sequence and 2D folding calculated from thermodynamical criteria – and their possible mutational changes, to the assumptions of a previously less detailed toy model. Results For each mutable nucleotide sequence the corresponding 2D folded structure with minimum free energy is calculated, which in turn is used to determine the fitness components (degradation rate, replicability and metabolic enzyme activity) of the Replicator. We show that the community of such Replicators providing the monomer supply for their own replication by evolving metabolic enzyme activities features an improved propensity for stable coexistence and structural adaptation. These evolutionary advantages are due to the emergent uniformity of metabolic Replicator fitnesses imposed on the community by local group selection and attained through Replicator trait convergence, i.e., the tendency of Replicator lengths, ribozyme activities and population sizes to become similar between the coevolving Replicator species that are otherwise both structurally and functionally different. Conclusions In the most general terms it is the surprisingly high extra viability of the metabolic Replicator system that the present model adds to the MCRS concept of the origin of life. Surface-bound, metabolically coupled RNA Replicators tend to evolve different, enzymatically active sites within thermodynamically stable secondary structures, and the system as a whole evolves towards the robust coexistence of a complete set of such ribozymes driving the metabolism producing monomers for their own replication. Reviewers This article was reviewed by Gáspár Jékely, Anthony Poole and Armen Mulkidjanian
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spatial aspects of prebiotic Replicator coexistence and community stability in a surface bound rna world model
BMC Evolutionary Biology, 2013Co-Authors: Balazs Konnyű, Tamas CzaranAbstract:The coexistence of macromolecular Replicators and thus the stability of presumed prebiotic Replicator communities have been shown to critically depend on spatially constrained catalytic cooperation among RNA-like modular Replicators. The necessary spatial constraints might have been supplied by mineral surfaces initially, preceding the more effective compartmentalization in membrane vesicles which must have been a later development of chemical evolution. Using our surface-bound RNA world model – the Metabolic Replicator Model (MRM) platform – we show that the mobilities on the mineral substrate surface of both the macromolecular Replicators and the small molecules of metabolites they produce catalytically are the key factors determining the stable persistence of an evolvable metabolic Replicator community. The effects of Replicator mobility and metabolite diffusion on different aspects of Replicator coexistence in MRM are determined, including the maximum attainable size of the metabolic Replicator system and its resistance to the invasion of parasitic Replicators. We suggest a chemically plausible hypothetical scenario for the evolution of the first protocell starting from the surface-bound MRM system.
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The evolution of enzyme specificity in the metabolic Replicator model of prebiotic evolution.
PloS one, 2011Co-Authors: Balazs Konnyű, Tamas CzaranAbstract:The chemical machinery of life must have been catalytic from the outset. Models of the chemical origins have attempted to explain the ecological mechanisms maintaining a minimum necessary diversity of prebiotic Replicator enzymes, but little attention has been paid so far to the evolutionary initiation of that diversity. We propose a possible first step in this direction: based on our previous model of a surface-bound metabolic Replicator system we try to explain how the adaptive specialization of enzymatic Replicator populations might have led to more diverse and more efficient communities of cooperating Replicators with two different enzyme activities. The key assumptions of the model are that mutations in the Replicator population can lead towards a) both of the two different enzyme specificities in separate Replicators: efficient “specialists” or b) a “generalist” Replicator type with both enzyme specificities working at less efficiency, or c) a fast-replicating, non-enzymatic “parasite”. We show that under realistic trade-off constraints on the phenotypic effects of these mutations the evolved Replicator community will be usually composed of both types of specialists and of a limited abundance of parasites, provided that the Replicators can slowly migrate on the mineral surface. It is only at very weak trade-offs that generalists take over in a phase-transition-like manner. The parasites do not seriously harm the system but can freely mutate, therefore they can be considered as pre-adaptations to later, useful functions that the metabolic system can adopt to increase its own fitness.
Nobuto Takeuchi - One of the best experts on this subject based on the ideXlab platform.
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evolutionary dynamics of rna like Replicator systems a bioinformatic approach to the origin of life
Physics of Life Reviews, 2012Co-Authors: Nobuto Takeuchi, Paulien HogewegAbstract:We review computational studies on prebiotic evolution, focusing on informatic processes in RNA-like Replicator systems. In particular, we consider the following processes: the maintenance of information by Replicators with and without interactions, the acquisition of information by Replicators having a complex genotype-phenotype map, the generation of information by Replicators having a complex genotype-phenotype-interaction map, and the storage of information by Replicators serving as dedicated templates. Focusing on these informatic aspects, we review studies on quasi-species, error threshold, RNA-folding genotype-phenotype map, hypercycle, multilevel selection (including spatial self-organization, classical group selection, and compartmentalization), and the origin of DNA-like Replicators. In conclusion, we pose a future question for theoretical studies on the origin of life.
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on the origin of dna genomes evolution of the division of labor between template and catalyst in model Replicator systems
PLOS Computational Biology, 2011Co-Authors: Nobuto Takeuchi, Paulien Hogeweg, Eugene V KooninAbstract:The division of labor between template and catalyst is a fundamental property of all living systems: DNA stores genetic information whereas proteins function as catalysts. The RNA world hypothesis, however, posits that, at the earlier stages of evolution, RNA acted as both template and catalyst. Why would such division of labor evolve in the RNA world? We investigated the evolution of DNA-like molecules, i.e. molecules that can function only as template, in minimal computational models of RNA Replicator systems. In the models, RNA can function as both template-directed polymerase and template, whereas DNA can function only as template. Two classes of models were explored. In the surface models, Replicators are attached to surfaces with finite diffusion. In the compartment models, Replicators are compartmentalized by vesicle-like boundaries. Both models displayed the evolution of DNA and the ensuing division of labor between templates and catalysts. In the surface model, DNA provides the advantage of greater resistance against parasitic templates. However, this advantage is at least partially offset by the disadvantage of slower multiplication due to the increased complexity of the replication cycle. In the compartment model, DNA can significantly delay the intra-compartment evolution of RNA towards catalytic deterioration. These results are explained in terms of the trade-off between template and catalyst that is inherent in RNA-only replication cycles: DNA releases RNA from this trade-off by making it unnecessary for RNA to serve as template and so rendering the system more resistant against evolving parasitism. Our analysis of these simple models suggests that the lack of catalytic activity in DNA by itself can generate a sufficient selective advantage for RNA Replicator systems to produce DNA. Given the widespread notion that DNA evolved owing to its superior chemical properties as a template, this study offers a novel insight into the evolutionary origin of DNA.
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The evolution of strand preference in simulated RNA Replicators with strand displacement: Implications for the origin of transcription
Biology direct, 2008Co-Authors: Nobuto Takeuchi, Laura Salazar, Anthony M. Poole, Paulien HogewegAbstract:Background: The simplest conceivable example of evolving systems is RNA molecules that can replicate themselves. Since replication produces a new RNA strand complementary to a template, all templates would eventually become double-stranded and, hence, become unavailable for replication. Thus the problem of how to separate the two strands is considered a major issue for the early evolution of self-replicating RNA. One biologically plausible way to copy a doublestranded RNA is to displace a preexisting strand by a newly synthesized strand. Such copying can in principle be initiated from either the (+) or (-) strand of a double-stranded RNA. Assuming that only one of them, say (+), can act as replicase when single-stranded, strand displacement produces a new replicase if the (-) strand is the template. If, however, the (+) strand is the template, it produces a new template (but no replicase). Modern transcription exhibits extreme strand preference wherein anti-sense strands are always the template. Likewise, replication by strand displacement seems optimal if it also exhibits extreme strand preference wherein (-) strands are always the template, favoring replicase production. Here we investigate whether such strand preference can evolve in a simple RNA Replicator system with strand displacement. Results: We first studied a simple mathematical model of the Replicator dynamics. Our results indicated that if the system is well-mixed, there is no selective force acting upon strand preference per se. Next, we studied an individual-based simulation model to investigate the evolution of strand preference under finite diffusion. Interestingly, the results showed that selective forces “emerge” because of finite diffusion. Strikingly, the direction of the strand preference that evolves [i.e. (+) or (-) strand excess] is a complex non-monotonic function of the diffusion intensity. The mechanism underlying this behavior is elucidated. Furthermore, a speciation-like phenomenon is observed under certain conditions: two extreme replication strategies, namely replicase producers and template producers, emerge and coexist among competing Replicators.
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The Role of Complex Formation and Deleterious Mutations for the Stability of RNA-Like Replicator Systems
Journal of Molecular Evolution, 2007Co-Authors: Nobuto Takeuchi, Paulien HogewegAbstract:In the RNA world hypothesis, RNA(-like) self-Replicators are suggested as the central player of prebiotic evolution. However, there is a serious problem in the evolution of complexity in such Replicators, i.e., the problem of parasites. Parasites, which are replicated by catalytic Replicators (catalysts), but do not replicate the others, can destroy a whole Replicator system by exploitation. Recently, a theoretical study underlined complex formation between Replicators—an often neglected but realistic process—as a stabilizing factor in a Replicator system by demonstrating that complex formation can shift the viable range of diffusion intensity to higher values. In the current study, we extend the previous study of complex formation. Firstly, by investigating a well-mixed Replicator system, we establish that complex formation gives parasites an implicit advantage over catalysts, which makes the system significantly more vulnerable to parasites. Secondly, by investigating a spatially extended Replicator system, we show that the formation of traveling wave patterns plays a crucial role in the stability of the system against parasites, and that because of this the effect of complex formation is not straightforward; i.e., whether complex formation stabilizes or destabilizes the spatial system is a complex function of other parameters. We give a detailed analysis of the spatial system by considering the pattern dynamics of waves. Furthermore, we investigate the effect of deleterious mutations. Surprisingly, high mutation rates can weaken the exploitation of the catalyst by the parasite.
Eörs Szathmáry - One of the best experts on this subject based on the ideXlab platform.
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From self-replication to Replicator systems en route to de novo life
Nature Reviews Chemistry, 2020Co-Authors: Paul Adamski, Tamas Czaran, András Szilágyi, Eörs Szathmáry, Adam Kun, Marcel Eleveld, Ankush Sood, Sijbren OttoAbstract:The process by which chemistry can give rise to biology remains one of the biggest mysteries in contemporary science. The de novo synthesis and origin of life both require the functional integration of three key characteristics — replication, metabolism and compartmentalization — into a system that is maintained out of equilibrium and is capable of open-ended Darwinian evolution. This Review takes systems of self-replicating molecules as starting points and describes the steps necessary to integrate additional characteristics of life. We analyse how far experimental self-Replicators have come in terms of Darwinian evolution. We also cover models of Replicator communities that attempt to solve Eigen’s paradox, whereby accurate replication needs complex machinery yet obtaining such complex self-Replicators through evolution requires accurate replication. Successful models rely on a collective metabolism and a way of (transient) compartmentalization, suggesting that the invention and integration of these two characteristics is driven by evolution. Despite our growing knowledge, there remain numerous key challenges that may be addressed by a combined theoretical and experimental approach. Self-replicating systems play a central role in the emergence of life. This Review describes the features that self-replicating systems need to acquire to transition from chemistry to biology and surveys the progress made in theoretical and experimental approaches.
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On the propagation of a conceptual error concerning hypercycles and cooperation
Journal of Systems Chemistry, 2013Co-Authors: Eörs SzathmáryAbstract:The hypercycle is a system of Replicators, whose members are auto- and cross-catalytic: replication of each member is catalyzed by at least one other member of the system. Therefore, the kinetics of growth of every member is at least second order. In ecology such systems are called mutualistic whose members are cooperating with each other. The dynamics of such systems are described broadly by the Replicator equation. In chemistry hypercycles are often confused with collectively autocatalytic systems in which the members catalyze each other’s formation rather than replication (growth being therefore first-order). Examples of this confusion abound in the literature. The trouble is that such category errors mistakenly imply that the available theories of hypercycles and cooperation are applicable, although in fact they are not. Cooperation in population biology means a higher-order interaction among agents with (at least the capacity of) multiplication. From the point of evolution, what matters is the genetic effects on the cooperative act. As systems chemistry has one of its roots in the theoretical biology, insights from this field ought to be respected even by experimentalists, let alone theoreticians.
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the neuronal Replicator hypothesis
Neural Computation, 2010Co-Authors: Chrisantha Fernando, Richard A Goldstein, Eörs SzathmáryAbstract:We propose that replication (with mutation) of patterns of neuronal activity can occur within the brain using known neurophysiological processes. Thereby evolutionary algorithms implemented by neuro-nal circuits can play a role in cognition. Replication of structured neuronal representations is assumed in several cognitive architectures. Replicators overcome some limitations of selectionist models of neuronal search. Hebbian learning is combined with replication to structure exploration on the basis of associations learned in the past. Neuromodulatory gating of sets of bistable neurons allows patterns of activation to be copied with mutation. If the probability of copying a set is related to the utility of that set, then an evolutionary algorithm can be implemented at rapid timescales in the brain. Populations of neuronal Replicators can undertake a more rapid and stable search than can be achieved by serial modification of a single solution. Hebbian learning added to neuronal replication allows a powerful structuring of variability capable of learning the location of a global optimum from multiple previously visited local optima. Replication of solutions can solve the problem of catastrophic forgetting in the stability-plasticity dilemma. In short, neuronal replication is essential to explain several features of flexible cognition. Predictions are made for the experimental validation of the neuronal Replicator hypothesis.
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The origin of Replicators and reproducers
Philosophical transactions of the Royal Society of London. Series B Biological sciences, 2006Co-Authors: Eörs SzathmáryAbstract:Replicators are fundamental to the origin of life and evolvability. Their survival depends on the accuracy of replication and the efficiency of growth relative to spontaneous decay. Infrabiological systems are built of two coupled autocatalytic systems, in contrast to minimal living systems that must comprise at least a metabolic subsystem, a hereditary subsystem and a boundary, serving respective functions. Some scenarios prefer to unite all these functions into one primordial system, as illustrated in the lipid world scenario, which is considered as a didactic example in detail. Experimentally produced chemical Replicators grow parabolically owing to product inhibition. A selection consequence is survival of everybody. The chromatographized Replicator model predicts that such Replicators spreading on surfaces can be selected for higher replication rate because double strands are washed away slower than single strands from the surface. Analysis of real ribozymes suggests that the error threshold of replication is less severe by about one order of magnitude than thought previously. Surface-bound dynamics is predicted to play a crucial role also for exponential Replicators: unlinked genes belonging to the same genome do not displace each other by competition, and efficient and accurate replicases can spread. The most efficient form of such useful population structure is encapsulation by reproducing vesicles. The stochastic corrector model shows how such a bag of genes can survive, and what the role of chromosome formation and intragenic recombination could be. Prebiotic and early evolution cannot be understood without the models of dynamics.
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The evolution of Replicators
Philosophical transactions of the Royal Society of London. Series B Biological sciences, 2000Co-Authors: Eörs SzathmáryAbstract:Replicators of interest in chemistry, biology and culture are briefly surveyed from a conceptual point of view. Systems with limited heredity have only a limited evolutionary potential because the number of available types is too low. Chemical cycles, such as the formose reaction, are holistic Replicators since replication is not based on the successive addition of modules. Replicator networks consisting of catalytic molecules (such as reflexively autocatalytic sets of proteins, or reproducing lipid vesicles) are hypothetical ensemble Replicators, and their functioning rests on attractors of their dynamics. Ensemble Replicators suffer from the paradox of specificity: while their abstract feasibility seems to require a high number of molecular types, the harmful effect of side reactions calls for a small system size. No satisfactory solution to this problem is known. Phenotypic Replicators do not pass on their genotypes, only some aspects of the phenotype are transmitted. Phenotypic Replicators with limited heredity include genetic membranes, prions and simple memetic systems. Memes in human culture are unlimited hereditary, phenotypic Replicators, based on language. The typical path of evolution goes from limited to unlimited heredity, and from attractor–based to modular (digital) Replicators.
