Figure 4 - uploaded by Kunihiko Kaneko
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The core network for the recursive state (with numbers in bold), and a part of the parasitic molecules (with numbers in italic).
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The origin of heredity is studied as a recursive state in a replicatingprotocell consisting of many molecule species in mutually catalyzingreaction networks. Protocells divide when the number of molecules, increasing due to replication, exceeds a certain threshold. We study how the chemicals in a catalytic network can form recursive production stat...
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Explanation of exponential growth in self-reproduction is an important step toward elucidation of the origins of life because optimization of the growth potential across rounds of selection is necessary for Darwinian evolution. To produce another copy with approximately the same composition, the exponential growth rates for all components have to b...
Citations
... Interface 20: 20230346 receives exactly one copy of each chromosome, the consolidation of a genome allows for reliable inheritance even when there are very large numbers of ACs and insufficient space for all of them to be represented by enough member molecules that both offspring cells reliably receive the full complement. Mathematical models have demonstrated that given a protocell with analogue inheritance involving many RNA molecules, a single master genome can gradually evolve [76,77]. ...
Prior research on evolutionary mechanisms during the origin of life has mainly assumed the existence of populations of discrete entities with information encoded in genetic polymers. Recent theoretical advances in autocatalytic chemical ecology establish a broader evolutionary framework that allows for adaptive complexification prior to the emergence of bounded individuals or genetic encoding. This framework establishes the formal equivalence of cells, ecosystems and certain localized chemical reaction systems as autocatalytic chemical ecosystems (ACEs): food-driven (open) systems that can grow due to the action of autocatalytic cycles (ACs). When ACEs are organized in meta-ecosystems, whether they be populations of cells or sets of chemically similar environmental patches, evolution, defined as change in AC frequency over time, can occur. In cases where ACs are enriched because they enhance ACE persistence or dispersal ability, evolution is adaptive and can build complexity. In particular, adaptive evolution can explain the emergence of self-bounded units (e.g. protocells) and genetic inheritance mechanisms. Recognizing the continuity between ecological and evolutionary change through the lens of autocatalytic chemical ecology suggests that the origin of life should be seen as a general and predictable outcome of driven chemical ecosystems rather than a phenomenon requiring specific, rare conditions.
... In a cell, however, a variety o f c hemicals form a complex reaction network to synthesize themselves. Here we study a model with a large number of chemical species, to discuss how a cell with such large number of components and complex reaction network can sustain reproduction, keeping similar chemical compositions [32,33](see also [34]). ...
... In our model there are four basic parameters; the total number of molecules N , the total number of molecule species k, the mutation rate , and the reaction path rate . By carrying out simulations of this model, choosing a variety of parameter values N; k; ; , also by taking various random networks, we have found that the behaviors are classied into the following three phases [32,33]: ...
In spite of recent advances, there still remains a large gape between a
set of chemical reactions and a biological cell. Here we discuss several
theoretical efforts to fill in the gap. The topics cover (i) slow
relaxation to equilibrium due to glassy behavior in catalytic reaction
networks (ii) consistency between molecule replication and cell growth,
as well as energy metabolism (iii) control of a system by minority
molecules in mutually catalytic system, which work as a carrier of
genetic information, and leading to evolvability (iv) generation of a
compartmentalized structure as a cluster of molecules centered around
the minority molecule, and division of the cluster accompanied by the
replication of minority molecule (v) sequential, logical process over
several states from concurrent reaction dynamics, by taking advantage of
discreteness in molecule number.
... At the same time, the cell serves as a micro-scale container that maintains chemical reactions over generations. Although such recursive reactors are ubiquitous in the biological world, it is not obvious what properties should arise from such growing and dividing micro-compartments [2]. One of the intriguing properties of proliferating cells is that while they repeatedly change size during growth and division, they have volume distributions that are specific to each cell species [3,4]. ...
Living cells replicate by passing through cycles of growth and division, and they act as containers for chemical reactions. To determine basic properties of such recursively growing and dividing micro-compartments, we constructed a model system in a micro-fluidic device. In this system, droplets in a water-in-oil emulsion underwent cycles of fusion and subsequent division with nutrient-mimicking droplets. We found that repeating the combinations of growth (by fusion) and division of the droplets brought about their steady size distribution that had a skewed shape, similar to that which had been observed for proliferating cells. Our numerical analysis suggested that the skewness was originated from stochasticity in the addition of volumes in the growth process.
... It is widely accepted that the appearance of self-reproducing protocells must have involved the emergence of networks of mutually interacting molecules, so as to resemble present-day cells (Bagley and Farmer 1991;Farmer et al. 1986;Jain and Krishna 2001;Kaneko 2002;Kauffman 1993;Shenhav et al. 2005b). What is still undecided is the nature of the specific molecules that involved in such a process. ...
... One major scenario claims that life began with a single self-replicating molecule, e.g., RNA (Gesteland et al. 2000;Gilbert 1986;Joyce 2002), which later evolved into networks instructed by the replicating biopolymers. An alternative scenario claims that as early as replicating entities have emerged, they must have constituted relatively complex molecular networks, arising via spontaneous accretion of weakly bound assemblies of simpler organic molecules (Bachmann et al. 1992; Barandiaran and Ruiz-Mirazo 2008;Benko et al. 2003;Dyson 1999;Jain and Krishna 2002;Kaneko 2002;Kauffman 1993;Luisi et al. 1999;Ruiz-Mirazo and Moreno 2004;Segre et al. , 2001Shapiro 2006;Shenhav et al. 2003;Stadler 1991;Morowitz 1992). In this alternative scenario it is further proposed that assembly reproduction directly stems from certain network attributes. ...
... An important operating principle previously shown to be shared between GARD and present-day life is a capacity to undergo reproduction-like processes. This general concept is embodied in several additional approaches indicating information transfer in entities that do not explicitly contain templating biopolymers (Etxeberria and Ruiz-Mirazo 2009;Krishna 2001, 2002;Kaneko 2002Kaneko , 2003Ruiz-Mirazo and Moreno 2004) and display autonomy and self construction. In GARD, it is manifested in the transmission of compositional information from an ancestor assembly to its progeny. ...
The Graded Autocatalysis Replication Domain (GARD) model describes an origin of life scenario which involves non-covalent compositional assemblies, made of monomeric mutually catalytic molecules. GARD constitutes an alternative to informational biopolymers as a mechanism of primordial inheritance. In the present work, we examined the effect of mutations, one of the most fundamental mechanisms for evolution, in the context of the networks of mutual interaction within GARD prebiotic assemblies. We performed a systematic analysis analogous to single and double gene deletions within GARD. While most deletions have only a small effect on both growth rate and molecular composition of the assemblies, ~10% of the deletions caused lethality, or sometimes showed enhanced fitness. Analysis of 14 different network properties on 2,000 different GARD networks indicated that lethality usually takes place when the deleted node has a high molecular count, or when it is a catalyst for such node. A correlation was also found between lethality and node degree centrality, similar to what is seen in real biological networks. Addressing double knockout mutations, our results demonstrate the occurrence of both synthetic lethality and extragenic suppression within GARD networks, and convey an attempt to correlate synthetic lethality to network node-pair properties. The analyses presented help establish GARD as a workable alternative prebiotic scenario, suggesting that life may have begun with large molecular networks of low fidelity, that later underwent evolutionary compaction and fidelity augmentation.
... We assume that the catalytic activity c(j) is chosen again from random number over [0; 1]. By carrying out simulations of this model, choosing a variety of parameter values N; k; ; p, a l s o b y taking various random networks, we h a ve found that the behaviors are classied into the following three types [Kaneko, 2002[Kaneko, ,2003a: ...
As an example of constructive biology, recursive production of a protocell is studied. Theory of minority control in a mutually catalytic reaction system is pre-sented, which gives a basis on the origin of bio-information. Recursive production states as well as switching among them in a catalytic reaction network system are studied numerically, where compositional information, evolvability, and universal uctuation law are discussed. As an experimental approach, construction of proto-cell is outlined. It consists of in-vitro autonomous replication system, replication of liposome, and RNA transcription and protein synthesis in liposome. Relevance of the minority control theory to sustain and evolve catalytic activity is demonstrated.
... This contends that certain life-like processes could have emerged prior to the synthesis of biopolymers (Morowitz H.J. et al. 1988; Wachtershauser 1988; Szathmary 2000; Shenhav et al. 2003). Such life-like entities may have been driven by mechanisms of mutual catalysis among constituent organic molecules (Kauffman 1993; Stadler et al. 1993; Dyson 1999; Jain and Krishna 2001; Kaneko 2002). Furthermore, according to this school of thought, biopolymers could be the result of primitive selection and rudimentary evolution rather than prerequisites for them. ...
The basic Graded Autocatalysis Replication Domain (GARD) model consists of a repertoire of small molecules, typically amphiphiles, which join and leave a non-covalent micelle-like assembly. Its replication behavior is due to occasional fission, followed by a homeostatic growth process governed by the assembly's composition. Limitations of the basic GARD model are its small finite molecular repertoire and the lack of a clear path from a 'monomer world' towards polymer-based living entities. We have now devised an extension of the model (polymer GARD or P-GARD), where a monomer-based GARD serves as a 'scaffold' for oligomer formation, as a result of internal chemical rules. We tested this concept with computer simulations of a simple case of monovalent monomers, whereby more complex molecules (dimers) are formed internally, in a manner resembling biosynthetic metabolism. We have observed events of dimer 'take-over' - the formation of compositionally stable, replication-prone quasi stationary states (composomes) that have appreciable dimer content. The appearance of novel metabolism-like networks obeys a time-dependent power law, reminiscent of evolution under punctuated equilibrium. A simulation under constant population conditions shows the dynamics of takeover and extinction of different composomes, leading to the generation of different population distributions. The P-GARD model offers a scenario whereby biopolymer formation may be a result of rather than a prerequisite for early life-like processes.
... One of the authors, Kaneko, and Yomo recently provided the "Minority Control conjecture," which propounds that chemical species with a small number of molecules governs the behavior of a replicating system, which is related to the origin of heredity [17,18,19]. Matsuura et al. experimentally demonstrated that a small number of genetic molecules is essential for evolution [20]. ...
To study the dynamics of chemical processes, we often adopt rate equations to observe the change in chemical concentrations. However, when the number of the molecules is small, the fluctuations cannot be neglected. We often study the effects of fluctuations with the help of stochastic differential equations. Chemicals are composed of molecules on a microscopic level. In principle, the number of molecules must be an integer, which must only change discretely. However, in analysis using stochastic differential equations, the fluctuations are regarded as continuous changes. This approximation can only be valid if applied to fluctuations that involve a sufficiently large number of molecules. In the case of extremely rare chemical species, the actual discreteness of the molecules may critically affect the dynamics of the system. To elucidate the effects of the discreteness, we study an autocatalytic system consisting of several interacting chemical species with a small number of molecules through stochastic particle simulations. We found novel states, which were characterized as an extinction of molecule species, due to the discrete nature of the molecules. We also observed a strong dependence of the chemical concentrations on the size of the system, which was caused by transitions to the novel states.
... In a cell, however, a variety of chemicals form a complex reaction network to synthesize themselves. Here we study a model with a large number of chemical species, to discuss how a cell with such large number of components and complex reaction network can sustain reproduction, keeping similar chemical compositions [32,33](see also [34]). ...
... In our model there are four basic parameters; the total number of molecules N , the total number of molecule species k, the mutation rate µ, and the reaction path rate ρ. By carrying out simulations of this model, choosing a variety of parameter values N, k, µ, ρ, also by taking various random networks, we have found that the behaviors are classified into the following three phases [32,33]: ...
To unveil the logic of cell from a level of chemical reaction dynamics, we need to clarify how ensemble of chemicals can autonomously produce the set of chemical, without assuming a specific external control mechanism. A cell consists of a huge number of chemical species that catalyze each other. Often the number of each molecule species is not so large, and accordingly the number fluctuations in each molecule species can be large. In the amidst of such diversity and large fluctuations, how can a cell make recursive production? On the other hand, a cell can change its state to evolve to a different type over a longer time span. How are reproduction and evolution compatible? We address these questions, based on several model studies with catalytic reaction network.
Life is that which replicates and evolves, but there is no consensus on how life emerged. We advocate a systems protobiology view, whereby the first replicators were assemblies of spontaneously accreting, heterogeneous and mostly non-canonical amphiphiles. This view is substantiated by rigorous chemical kinetics simulations of the graded autocatalysis replication domain (GARD) model, based on the notion that the replication or reproduction of compositional information predated that of sequence information. GARD reveals the emergence of privileged non-equilibrium assemblies (composomes), which portray catalysis-based homeostatic (concentration-preserving) growth. Such a process, along with occasional assembly fission, embodies cell-like reproduction. GARD pre-RNA evolution is evidenced in the selection of different composomes within a sparse fitness landscape, in response to environmental chemical changes. These observations refute claims that GARD assemblies (or other mutually catalytic networks in the metabolism first scenario) cannot evolve. Composomes represent both a genotype and a selectable phenotype, anteceding present-day biology in which the two are mostly separated. Detailed GARD analyses show attractor-like transitions from random assemblies to self-organized composomes, with negative entropy change, thus establishing composomes as dissipative systems-hallmarks of life. We show a preliminary new version of our model, metabolic GARD (M-GARD), in which lipid covalent modifications are orchestrated by non-enzymatic lipid catalysts, themselves compositionally reproduced. M-GARD fills the gap of the lack of true metabolism in basic GARD, and is rewardingly supported by a published experimental instance of a lipid-based mutually catalytic network. Anticipating near-future far-reaching progress of molecular dynamics, M-GARD is slated to quantitatively depict elaborate protocells, with orchestrated reproduction of both lipid bilayer and lumenal content. Finally, a GARD analysis in a whole-planet context offers the potential for estimating the probability of life's emergence. The invigorated GARD scrutiny presented in this review enhances the validity of autocatalytic sets as a bona fide early evolution scenario and provides essential infrastructure for a paradigm shift towards a systems protobiology view of life's origin.
Life system is both complex and complicated [12]. These two features have to be distinguished. In a complicated system, many factors are involved and the possible variety of combination of such factors is enormous. It requires hard efforts to disintegrate it into parts, but in principle it is possible. Indeed in the bioinformatics, studies along this direction are carried forward with the aid of computer. On the other hand, in “complex systems”, one has to face the circular relationship in which each part is understood only through the relationship with the whole, although the whole, of course, consists of parts. In the complex systems approach, we try to understand universal logic that biological systems have to obey through such dynamic circulation between the whole and parts. Here we are not concerned with determining a specific role of a molecule or a biochemical process; Rather we intend to understand some universal features that a class of biological systems exhibit, irrespectively of details.
