Emergence of protocellular growth laws

Template-directed replication is known to obey a parabolic growth law due to product inhibition (Sievers & Von Kiedrowski 1994 Nature 369, 221; Lee et al. 1996 Nature 382, 525; Varga & Szathmáry 1997 Bull. Math. Biol. 59, 1145). We investigate a template-directed replication with a coupled template catalysed lipid aggregate production as a model of a minimal protocell and show analytically that the autocatalytic template-container feedback ensures balanced exponential replication kinetics; both the genes and the container grow exponentially with the same exponent. The parabolic gene replication does not limit the protocellular growth, and a detailed stoichiometric control of the individual protocell components is not necessary to ensure a balanced gene-container growth as conjectured by various authors (Gánti 2004 Chemoton theory). Our analysis also suggests that the exponential growth of most modern biological systems emerges from the inherent spatial quality of the container replication process as we show analytically how the internal gene and metabolic kinetics determine the cell population's generation time and not the growth law (Burdett & Kirkwood 1983 J. Theor. Biol. 103, 11-20; Novak et al. 1998 Biophys. Chem. 72, 185-200; Tyson et al. 2003 Curr. Opin. Cell Biol. 15, 221-231). Previous extensive replication reaction kinetic studies have mainly focused on template replication and have not included a coupling to metabolic container dynamics (Stadler et al. 2000 Bull. Math. Biol. 62, 1061-1086; Stadler & Stadler 2003 Adv. Comp. Syst. 6, 47). The reported results extend these investigations. Finally, the coordinated exponential gene-container growth law stemming from catalysis is an encouraging circumstance for the many experimental groups currently engaged in assembling self-replicating minimal artificial cells (Szostak 2001 et al. Nature 409, 387-390; Pohorille & Deamer 2002 Trends Biotech. 20 123-128; Rasmussen et al. 2004 Science 303, 963-965; Szathma ry 2005 Nature 433, 469-470; Luisi et al. 2006 Naturwissenschaften 93, 1-13).     

Imitational modeling of process of evolution: From organic macromolecules to protocell and animal cell

A dynamic imitational model of initial stages of cell evolution has been developed based on role of environmental calcium concentration. The model is designed from our hypothesis about the medium of the appearance of protocells, which could be potassium water reservoirs rather than sea salt water with its predominance of sodium salts. The necessary elements of the appearance of the protocells served organic molecules, code of their synthesis, and formation of macromolecules under favorable ion concentration in environment: a high K⁺ and Mg²⁺ and a low Na⁺ concentration. The model is based on an assumption that one of the first stages in evolution of life was the appearance in the potassium-magnesium water reservoirs of organic molecules capable for self-replication on the basis of genetic code and formation of protocell with the potassium cytoplasm. The model has demonstrated necessity of formation of cell envelope for development of the protocell. Replacement of the dominant cation in water reservoirs—potassium by sodium—required the appearance of ion-transporting devices in plasma membrane and their participation in adaptation of cells to environment. This stage of evolution was accompanied by the most important morphofunctional event—formation of the plasma membrane instead of cell envelope. The membrane provided the ion asymmetry in the cell (preservation of K⁺ in it) relatively to the sodium external medium for maintaining optimal intracellular medium. In the model system, predecessors of animal cells elaborated mechanism of maintenance of the potassium cytoplasm with the sodium counterion dominating in the environment.     

Coevolution of compositional protocells and their environment

The coevolution of environment and living organisms is well known in nature. Here, it is suggested that similar processes can take place before the onset of life, where protocellular entities, rather than full-fledged living systems, coevolve along with their surroundings. Specifically, it is suggested that the chemical composition of the environment may have governed the chemical repertoire generated within molecular assemblies, compositional protocells, while compounds generated within these protocells altered the chemical composition of the environment. We present an extension of the graded autocatalysis replication domain (GARD) model--the environment exchange polymer GARD (EE-GARD) model. In the new model, molecules, which are formed in a protocellular assembly, may be exported to the environment that surrounds the protocell. Computer simulations of the model using an infinite-sized environment showed that EE-GARD assemblies may assume several distinct quasi-stationary compositions (composomes), similar to the observations in previous variants of the GARD model. A statistical analysis suggested that the repertoire of composomes manifested by the assemblies is independent of time. In simulations with a finite environment, this was not the case. Composomes, which were frequent in the early stages of the simulation disappeared, while others emerged. The change in the frequencies of composomes was found to be correlated with changes induced on the environment by the assembly. The EE-GARD model is the first GARD model to portray a possible time evolution of the composomes repertoire.     

Generic Darwinian selection in catalytic protocell assemblies

To satisfy the minimal requirements for life, an information carrying molecular structure must be able to convert resources into building blocks and also be able to adapt to or modify its environment to enhance its own proliferation. Furthermore, new copies of itself must have variable fitness such that evolution is possible. In practical terms, a minimal protocell should be characterized by a strong coupling between its metabolism and genetic subsystem, which is made possible by the container. There is still no general agreement on how such a complex system might have been naturally selected for in a prebiotic environment. However, the historical details are not important for our investigations as they are related to assembling and evolution of protocells in the laboratory. Here, we study three different minimal protocell models of increasing complexity, all of them incorporating the coupling between a 'genetic template', a container and, eventually, a toy metabolism. We show that for any local growth law associated with template self-replication, the overall temporal evolution of all protocell's components follows an exponential growth (efficient or uninhibited autocatalysis). Thus, such a system attains exponential growth through coordinated catalytic growth of its component subsystems, independent of the replication efficiency of the involved subsystems. As exponential growth implies the survival of the fittest in a competitive environment, these results suggest that protocell assemblies could be efficient vehicles in terms of evolving through Darwinian selection.     

An optimal degree of physical and chemical heterogeneity for the origin of life?

The accumulation of pure, concentrated chemical building blocks, from which the essential components of protocells could be assembled, has long been viewed as a necessary, but extremely difficult step on the pathway to the origin of life. However, recent experiments have shown that moderately increasing the complexity of a set of chemical inputs can in some cases lead to a dramatic simplification of the resulting reaction products. Similarly, model protocell membranes composed of certain mixtures of amphiphilic molecules have superior physical properties than membranes composed of single amphiphiles. Moreover, membrane self-assembly under simple and natural conditions gives rise to heterogeneous mixtures of large multi-lamellar vesicles, which are predisposed to a robust pathway of growth and division that simpler and more homogeneous small unilamellar vesicles cannot undergo. Might a similar relaxation of the constraints on building block purity and homogeneity actually facilitate the difficult process of nucleic acid replication? Several arguments suggest that mixtures of monomers and short oligonucleotides may enable the chemical copying of polynucleotides of sufficient length and sequence complexity to allow for the emergence of the first nucleic acid catalysts. The question of the origin of life may become less daunting once the constraints of overly well-defined laboratory experiments are appropriately relaxed.     

Vesicle encapsulation stabilizes intermolecular association and structure formation of functional RNA and DNA

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The emergence of ribozymes synthesizing membrane components in RNA-based protocells

A significant problem of the origin of life is the emergence of cellular self-replication. In the context of the “RNA world”, a crucial concern is how the RNA-based protocells could achieve the ability to produce their own membrane. Here we show, with the aid of a computer simulation, that for these protocells, there would be “immediately” a selection pressure for the emergence of a ribozyme synthesizing membrane components. The ribozyme would promote the enlargement of cellular space and favor the incoming (by permeation) of RNA's precursors, thus benefit the replication of inner RNA, including itself. Via growth and division, protocells containing the ribozyme would achieve superiority and spread in the system, and meanwhile the ribozyme would spread in the system. The present work is inspiring because it suggests that the transition from molecular self-replication to cellular self-replication might have occurred naturally (and necessarily) in the origin of life, leading to the emergence of Darwinian evolution at the cellular level.