Prebiological Evolution and the Andrew J. Pratt* Metabolic Origins of Life University of Canterbury Keywords Abiogenesis, origin of life, metabolism, hydrothermal, iron Abstract The chemoton model of cells posits three subsystems: metabolism, compartmentalization, and information. A specific model for the prebiological evolution of a reproducing system with rudimentary versions of these three interdependent subsystems is presented. This is based on the initial emergence and reproduction of autocatalytic networks in hydrothermal microcompartments containing iron sulfide. The driving force for life was catalysis of the dissipation of the intrinsic redox gradient of the planet. The codependence of life on iron and phosphate provides chemical constraints on the ordering of prebiological evolution. The initial protometabolism was based on positive feedback loops associated with in situ carbon fixation in which the initial protometabolites modified the catalytic capacity and mobility of metal-based catalysts, especially iron-sulfur centers. A number of selection mechanisms, including catalytic efficiency and specificity, hydrolytic stability, and selective solubilization, are proposed as key determinants for autocatalytic reproduction exploited in protometabolic evolution. This evolutionary process led from autocatalytic networks within preexisting compartments to discrete, reproducing, mobile vesicular protocells with the capacity to use soluble sugar phosphates and hence the opportunity to develop nucleic acids. Fidelity of information transfer in the reproduction of these increasingly complex autocatalytic networks is a key selection pressure in prebiological evolution that eventually leads to the selection of nucleic acids as a digital information subsystem and hence the emergence of fully functional chemotons capable of Darwinian evolution. 1 Introduction: Chemoton Subsystems and Evolutionary Pathways Living cells are autocatalytic entities that harness redox energy via the selective catalysis of biochemical transformations. The complexity of cells requires that they emerged from evolutionary processes that predate life: a form of prebiological evolution [71]. Understanding this prebiological evolution, and the selection processes that gave rise to the complexity of cells, is a key to unraveling the origin of life. The simplest model for cells is the chemoton model, which regards them as fluid automata [28]. Chemoton theory proposes that living cells are composed of three essential interconnected subsystems associated with metabolism, compartmentalization, and information. A metabolic subsystem is required to provide the building blocks and chemical energy for life. Compartmentalization is required for evolution to act * Department of Chemistry, University of Canterbury, Christchurch, PB4800, New Zealand. E-mail: [email protected] © 2011 Massachusetts Institute of Technology Artificial Life 17: 203–217 (2011) Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/artl_a_00032 by guest on 25 September 2021 A. J. Pratt Prebiological Evolution and the Metabolic Origins of Life on discrete competing entities. Finally, an information subsystem allows the evolution of levels of complexity that are a distinctive feature of life. A theory of the origin of life based on the chemoton, or a related model, must explain a clear pathway to the coexistence of these three interdependent subsystems [71]. Simultaneous creation of an entity with all three subsystems in place is exceedingly improbable [19]; it is more likely that cells arose via a pathway involving accretion of one or two subsystem(s) by a simpler system. There are competing perspectives based on the assumed timing of events. What comes first: compartments, information, and/or metabolism? The two main competing hypotheses both assume compartmentalization as an early feature, either via the self-assembly of membranes [17] or via surface adsorption [77]. They differ in the initially associated subsystem: information first or metabolism first. The closest synthetic models we have of partial chemotons are protocells based on lipid- encapsulated RNA molecules [31, 47]. These build on the demonstration of directed evolution within in vitro RNA systems [42] and the success of the RNA world hypothesis in exploring the dual ability of RNA molecules to act as both catalysts and stores of hereditary information [1]. However, an RNA world depends on the continued availability of complex raw materials, including sources of chemically activated nucleotides for polymerization, and of turnover of these materials to allow selection of func- tional macromolecular structures. A significant challenge for this model is to understand the energy flux that created and sustained an RNA world—in particular the underpinning functional metabolism that harnessed redox energy for the evolution of the system and that provided the basis for con- temporary biochemistry. In this model it is often assumed that metabolism emerges to replace spent preexisting metabolites. This model for the engineering of metabolic pathways backward to alternative starting materials, originally due to Horowitz [35], is out of step with recent insights into the evolution of biochemical metabolism [83] and unlikely to be the complete story. The competing viewpoint is that the first steps to life were based on compartmentalized proto- metabolism that subsequently developed an information subsystem. Wächtershäuser, Russell, de Duve, Morowitz, and others have developed models of this type in which protometabolic reactions are catalyzed and organized on iron sulfide surfaces [15, 62, 74, 77]. One major challenge for models based on networks of catalysts as initiators of life, such as those envisaged in the GARD model [66], is the limited evolvability of such systems [75]. This article presents a model for the origin of life that links iron-sulfur and RNA world models. It is proposed here that these two perspectives can be reconciled if there is a particular ordering of pre- biological events. The chemical constraints posed by two of the essential elements of life fundamental to these models, iron and phosphate, underpin this ordering. Iron catalysis is a key feature required for the development of protometabolic processes. Phosphate is a required building block of a sugar phosphate metabolism and of RNA itself. A fundamental problem is that phosphates precipitate in the presence of some free multivalent metal ions, notably iron and calcium. Precipitation of phosphates provides a concentration mechanism for this otherwise scarce resource that was likely to be a limiting nutrient for life at its inception [7]. However, precipitation compromises the development of a soluble metabolism that incorporates phosphate species [54]. Cells avoid this precipitation problem via a com- bination of encapsulation and exclusion of multivalent metal ions [27]. Essentially all iron within living cells is encapsulated within proteins either as iron mineral clusters or as porphyrin complexes. Both oligopeptides and porphyrins [24] are oligomers derivable from amino acid building blocks that are, in principle, accessible from plausible prebiotic catalysis. This is a key insight in developing a model for the ordering of events leading to life. It is proposed that self-organizing autocatalytic cycles based on iron predate the utilization of phosphate-containing protometabolites. The initial autocatalytic chem- istry gave rise to ligands that could encapsulate iron. Once the free metal iron levels were controlled in this way, it became possible for phosphates to be solubilized and hence integrated with an emerging protometabolism. As protometabolic systems became more complex, the reproduction of this informa- tion became a key selection mechanism for the emergence of protocells utilizing RNA. It is proposed that the RNA world, with vesicle-based compartmentalization, emerged in response to this demand for enhanced fidelity of information reproduction. An evolutionary account is presented that provides a series of specific chemical and physical selection mechanisms for the early stage development of a 204 Artificial Life Volume 17, Number 3 Downloaded from http://www.mitpressjournals.org/doi/pdf/10.1162/artl_a_00032 by guest on 25 September 2021 A. J. Pratt Prebiological Evolution and the Metabolic Origins of Life three-subsystem RNA world chemoton in which the RNA world emerges as a logical consequence of a prebiological (non-Darwinian) evolutionary process. 2 Protometabolism in Preexisting Compartments 2.1 Why and How Did Life Emerge? Life depends on a continuous input of energy that can fuel redox chemistry. This proposal follows the hypothesis of Russell and Kanik [64] that life emerged to exploit the intrinsic redox gradient of the earth that has existed since its origin. Reactive electron acceptors, such as oxygen, were scavenged when the earth formed. The residual components separated out into physically segregated domains. The electron- rich core of the earth was locked away beneath the crust, separated from a weakly oxidizing atmosphere containing carbon dioxide, nitrogen, and other moderate electron acceptors. The large store of potential energy in this physical segregation of the planet could be harnessed if and when there was mixing of chemicals from the electron-rich interior with exterior electron acceptors. For this reason, life emerged in pores [63] within hydrothermal mineral deposits where there is a mixing of these otherwise