385 research outputs found

    Modern views of ancient metabolic networks

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    Metabolism is a molecular, cellular, ecological and planetary phenomenon, whose fundamental principles are likely at the heart of what makes living matter different from inanimate one. Systems biology approaches developed for the quantitative analysis of metabolism at multiple scales can help understand metabolism's ancient history. In this review, we highlight work that uses network-level approaches to shed light on key innovations in ancient life, including the emergence of proto-metabolic networks, collective autocatalysis and bioenergetics coupling. Recent experiments and computational analyses have revealed new aspects of this ancient history, paving the way for the use of large datasets to further improve our understanding of life's principles and abiogenesis.https://www.sciencedirect.com/science/article/pii/S2452310017302196Published versio

    Twenty years of "Lipid World": a fertile partnership with David Deamer

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    "The Lipid World" was published in 2001, stemming from a highly effective collaboration with David Deamer during a sabbatical year 20 years ago at the Weizmann Institute of Science in Israel. The present review paper highlights the benefits of this scientific interaction and assesses the impact of the lipid world paper on the present understanding of the possible roles of amphiphiles and their assemblies in the origin of life. The lipid world is defined as a putative stage in the progression towards life's origin, during which diverse amphiphiles or other spontaneously aggregating small molecules could have concurrently played multiple key roles, including compartment formation, the appearance of mutually catalytic networks, molecular information processing, and the rise of collective self-reproduction and compositional inheritance. This review brings back into a broader perspective some key points originally made in the lipid world paper, stressing the distinction between the widely accepted role of lipids in forming compartments and their expanded capacities as delineated above. In the light of recent advancements, we discussed the topical relevance of the lipid worldview as an alternative to broadly accepted scenarios, and the need for further experimental and computer-based validation of the feasibility and implications of the individual attributes of this point of view. Finally, we point to possible avenues for exploring transition paths from small molecule-based noncovalent structures to more complex biopolymer-containing proto-cellular systems.711473 - Minerva Foundation; 80NSSC17K0295, 80NSSC17K0296, 1724150 - National Science FoundationPublished versio

    Systems-chemistry approach to prebiotic evolution

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    The puzzle of the origin of life is grand. A major challenge is to understand the transition from a mixture of molecules into an entity with basic life faculties, such as a protocell, capable of self-replication and inheritance. Two major schools tackle this problem: the genetic, or replicator-first approach, and the metabolism-first approach. The replicator-first approach focuses on a single self-perpetuating informational biopolymer, e.g., RNA, as the first step, and it is thus often referred to as the “RNA world”. In contrast, the metabolism-first approach focuses on a network of chemical reactions among simpler chemical components that became endowed with some reproductive characteristics as the first step that led to a protocell. The lipid world scenario, largely initiated by our laboratory, delineates a specific example of metabolism first. It suggests that spontaneously forming assemblies of relatively simple molecules, such as mutually interacting lipids, that resemble primitive metabolism, are capable of storing and transmitting information similar to sequence-based polymeric RNA, except that in this case it is compositional information that is at work. This thesis is about further exploration of the lipid world scenario, showing in more detail how a relatively simple chemical system can acquire features such as selection and evolution. This was accomplished by studying dynamical aspects of the graded autocatalysis replication domain (GARD) computer-simulation lipid world model, previously developed at our laboratory. GARD simulates the homeostatic growth of a compositional amphiphile assembly by reversible accretion from a buffered heterogeneous external pool. This process is governed by a network of mutually catalytic reactions, and exhibits quasi-stationary compositional states termed compotype, that may be regarded as GARD species. I have demonstrated that that such GARD species exhibit positive as well as negative selection, an important prerequisite of a minimally living system. I further showed that when the catalytic network becomes dominated by mutual catalysis, as opposed to self-catalysis, selection is enhanced. When studying the dynamics of large populations of GARD assemblies under constant population conditions, I rewardingly found that they exhibit dynamics similar to natural ecosystem populations, e.g. similes of competition or predator-prey dynamics. I was able to establish relationships between a compotype’s internal molecular parameters (e.g. its molecular diversity) and population ecology behavior. In a separate vein, I have developed a new approach towards observing open-ended evolution, which enables asking whether there is an optimal level of open endedness in prebiotic evolution. Finally, I was able to show clear similarities between GARD compotypes and quasispecies in the Eigen-Schuster model for evolution, further underlining GARD’s capacity as an alternative to RNA World. Taken together, these results uncover quantitative aspects of the GARD model which in turn contribute towards our understanding of the origin of life via the lipid world scenario

    "Minimal metabolism": A key concept to investigate the origins and nature of biological systems

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    The systems view on life and its emergence from complex chemistry has remarkably increased the scientific attention on metabolism in the last two decades. However, during this time there has not been much theoretical discussion on what constitutes a metabolism and what role it actually played in biogenesis. A critical and updated review on the topic is here offered, including some references to classical models from last century, but focusing more on current and future research. Metabolism is considered as intrinsically related to the living but not necessarily equivalent to it. More precisely, the idea of "minimal metabolism", in contrast to previous, top-down conceptions, is formulated as a heuristic construct, halfway between chemistry and biology. Thus, rather than providing a complete or final characterization of metabolism, our aim is to encourage further investigations on it, particularly in the context of life's origin, for which some concrete methodological suggestions are provided.This work was carried out as part of a Horizon 2020 Marie Curie ITN ("ProtoMet"-Grant Agreement no. 813873 with the European Commission), within which NL obtained a PhD fellowship. KR-M also acknowledges support from the Basque Government (Grant IT 122819) and the Spanish Ministry of Science and Innovation (PID2019-104576GB-I00

    Systems protobiology:Origin of life in lipid catalytic networks

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    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 systemstextemdashhallmarks 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

    Modelling Early Transitions Toward Autonomous Protocells

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    This thesis broadly concerns the origins of life problem, pursuing a joint approach that combines general philosophical/conceptual reflection on the problem along with more detailed and formal scientific modelling work oriented in the conceptual perspective developed. The central subject matter addressed is the emergence and maintenance of compartmentalised chemistries as precursors of more complex systems with a proper cellular organization. Whereas an evolutionary conception of life dominates prebiotic chemistry research and overflows into the protocells field, this thesis defends that the 'autonomous systems perspective' of living phenomena is a suitable - arguably the most suitable - conceptual framework to serve as a backdrop for protocell research. The autonomy approach allows a careful and thorough reformulation of the origins of cellular life problem as the problem of how integrated autopoietic chemical organisation, present in all full-fledged cells, originated and developed from more simple far-from-equilibrium chemical aggregate systems.Comment: 205 Pages, 27 Figures, PhD Thesis Defended Feb 201

    Life, An Evidence for Creation

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    The advanced state of understanding of the biochemistry of the bacterial cell, as evidenced by the knowledge of the complete nucleotide sequences of Haemophilus influenzae and Escherichia coli, allows the re·examination of the plausibility of the spontaneous generation of life. It is seen that in order to function these one·celled organisms require approximately 1700 and 4300 genes and gene products respectively. In the living state, none of the chemical reactions, though catalyzed very efficiently by specific enzymes, is allowed to reach its end point. The phenomenon of life depends on the steady state, nonequilibrium condition of all chemical reactions. This is the consequence of two features. One, the design of the substrates and their catalysts causes the dove-tailing of chemical changes into interconnected biochemical assembly lines. During growth, the influx of carbon, nitrogen etc. and energy sources is balanced by the utilization of the end-products of biosynthetic pathways and the efflux of waste. Secondly, somewhere in the past, these biochemical chain-reactions were ignited successfully, and they continue uninterrupted since the dawn of life, over many generations. This is recognized by the biologist\u27s dictum: life comes from life . Forty five years of futile laboratory efforts to demonstrate the plausibility of spontaneous abiogenesis have underscored the incredibility of the postulates of chemical evolution. Furthermore, the inability of modem biochemists to generate living matter even non spontaneously, drives home the concept that life was created by an Intelligence far exceeding ours

    Primal Eukaryogenesis:On the Communal Nature of Precellular States, Ancestral to Modern Life

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    This problem-oriented, exploratory and hypothesis-driven discourse toward the unknown combines several basic tenets: (i) a photo-active metal sulfide scenario of primal biogenesis in the porespace of shallow sedimentary flats, in contrast to hot deep-sea hydrothermal vent conditions; (ii) an inherently complex communal system at the common root of present life forms; (iii) a high degree of internal compartmentalization at this communal root, progressively resembling coenocytic (syncytial) super-cells; (iv) a direct connection from such communal super-cells to proto-eukaryotic macro-cell organization; and (v) multiple rounds of micro-cellular escape with streamlined reductive evolution—leading to the major prokaryotic cell lines, as well as to megaviruses and other viral lineages. Hopefully, such nontraditional concepts and approaches will contribute to coherent and plausible views about the origins and early life on Earth. In particular, the coevolutionary emergence from a communal system at the common root can most naturally explain the vast discrepancy in subcellular organization between modern eukaryotes on the one hand and both archaea and bacteria on the other
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