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 segregated zones of the planet. The driving force for the emergence of life was the so-called fourth law of thermo- dynamics, which proposes that systems with sufficient degrees of freedom self-organize to maximize the rate of entropy production [43, 70]. Life provided a mechanism to channel electrons ever more efficiently from the interior to the exterior of the earth, thereby allowing increasing rates of entropy generation. This feature of life continues to this day (now augmenting geochemical electron flux with solar-powered variants), with evidence pointing to the fact that ecosystems act in an analogous fashion to maximize the rate of entropy production [34]. It was not only the physical barrier to electron flow that was important for the fourth law to act and life to emerge. If electron transfer reactions were facile in hydrothermal mixing zones, then simple chemical processes would serve to dissipate the redox gradient directly, leaving no opportunity for complex autocatalytic networks to develop. Only if autocatalytic networks were more efficient at me- diating electron transfer than direct chemical processes could there be selection of complex systems. On this basis, it is proposed that the critical features of the earthʼs environment for the emergence of life were: (i) a continuous input of redox energy; (ii) a kinetic barrier to the dissipation of the intrinsic redox gradient; (iii) the availability of catalysts in a mixing zone that could speed dissipation of the gradient, but where initial catalysts were inefficient and capable of increased efficiency by diversification to networks of more specific catalysts; and (iv) protection against significant external shocks (irradiation, variations in pH and ionic strength, etc.) to facilitate protocell evolution by allowing the reproduction of catalytic networks as discrete entities. This environment provided an evolutionary opportunity for the emergence of networks of catalysts of increasing complexity and was necessary, but not sufficient, for life. There is a limit to the complexity of simple catalytic cycles, associated with limits to fidelity of reproduction [75]. It is proposed that life, as we know it, emerged when a digital information subsystem evolved that transcended the information limits of simple chemical networks and allowed open-ended Darwinian evolution with natural selection.
2.2 Iron-Sulfur Species and the Early Evolution of Catalytic Centers Following the patchwork model of evolution of biochemical catalysts [40], the best starting point for evolution is the availability of generic, but inefficient catalysts that are capable of evolving increased specificity and efficiency [71]. One key issue for self-organizing autocatalytic networks, highlighted by Orgel [52], is the need for a series of catalysts that mediate all the processes of the network. Iron-sulfur-based species [5] are well placed to fill this role, since they are capable of catalyzing a diverse range of both redox and acid-base chemistry. Much of this chemistry is utilized in contemporary core metabolism via iron-sulfur clusters that resemble iron sulfide mineral structures (Figure 1) [60]. Iron- sulfur clusters occur naturally in aqueous systems [61]. Biochemical clusters of this kind mediate the following processes: (i) bioenergetic electron-transfer processes (e.g., [11, 82]); (ii) other metabolic redox chemistry (e.g., carbon fixation [57], nitrogen fixation [23], reversible hydrogen formation [51],
Artificial Life Volume 17, Number 3 205
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
Figure 1. Iron-sulfur minerals and catalytic biochemical clusters. 1: mackinawite substructure; 2: [2Fe,2S] electron transfer cluster; 3: greigite substructure; 4: [4Fe,4S] electron transfer cluster; 5: acid-base catalyst (aconitase with citrate bound); 6: radical generating cluster (with S-adenosylmethionine bound, R = adenosyl); 7: model for Ni-substituted greigite; 8: carbon fixing cluster of ACS.
and organic radical chemistry [6, 50]); and (iii) a diverse range of acid-base chemistry, including hydration- dehydration chemistry (e.g., aconitase, serine dehydratase, and related enzymes [26]). The specific catalytic properties of iron-sulfur-dependent enzymes are controlled by the composition of the metal-sulfur cluster and the details of the coordinating ligands (Figure 1). For example, iron-sulfur clusters completely coordinated by sulfur ligands (2 and 4) act as specific electron transfer proteins in which the redox potential is moderated by cluster size and details [58]. Clusters, such as the [4Fe,4S] cluster in aconitase (5), with one nonsulfur coordination site, can undergo active metal and ligand exchange chemistry. Ligands, such as carboxylates, transiently bound to such clusters can undergo re- actions involving acid-base catalysis [26]. When bound to an iron-sulfur cluster, the amino acid deriva- tive S-adenosylmethionine is a source of organic radicals (6). Iron sulfide minerals contain other metal ions (7) [63]. The presence of adjacent metal ions (e.g., nickel, cobalt, and molybdenum) provides new distinctive catalytic chemistry that can exploit the electron transfer chemistry of iron sulfides. For example, nickel-iron-sulfur clusters are utilized in a number of enzymes, including both key en- zymes of the Wood-Ljungdahl carbon fixation pathway, CO dehydrogenase and acetyl-CoA synthase (8) [76]; likewise, molybdenum-iron-sulfur clusters are utilized in nitrogenase [23]. The ability to modify and control specific catalytic activities via coordination chemistry provides the potential for the evolution of catalysts of diversified specificity and activity in an emerging division of (protometabolic) labor. There is an opportunity for positive feedback loops in the interactions between metal-sulfur clusters and organic chemistry that underpins the development of an expanding web of protometabolic reactions. New protometabolites provide new catalytic opportunities for metal-sulfur clusters that, in turn, catalyze the formation and interconversion of new protometabolites.
2.3 Prebiotic Wood-Ljungdahl Carbon Fixation: The First Step The shortest and simplest known route to biological carbon fixation is the Wood-Ljungdahl pathway (Figure 2), in which carbon dioxide is reduced to carbon monoxide at an iron-nickel-sulfur center of CO dehydrogenase (CODH). The carbon monoxide is then transferred internally to acetyl CoA synthase (ACS), another iron-, nickel-, and sulfur-dependent enzyme, where it carbonylates a methyl-nickel species. The resulting acetyl nickel intermediate is intercepted by the thiol coenzyme A to produce acetyl CoA [29, 33, 65]. The methyl group is sourced from methyl tetrahydrofolate (CH3-THF) and is de- livered to this system by a cobalt corrinoid iron-sulfur protein (CFeSP) [69]. In this carbon fixation pathway the key manipulations of carbon species are mediated by nickel and cobalt centers with adjacent iron-sulfur clusters supplying electrons. In geochemical systems the initially deposited iron monosulfide is nanoparticulate mackinawite, which adsorbs divalent metal ions [81] such as nickel and cobalt. Huber and Wächtershäuser [37] have shown that inorganic iron-nickel sulfide catalyzes a simple analogue of acetyl CoA synthase chemistry in water, converting methanethiol to methyl thioacetate (Figure 2). The
206 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
product thioester is hydrolyzed under the reaction conditions to acetate, providing a strong overall thermodynamic driving force for the process [67]. This simple geochemistry immediately provides a positive feedback mechanism that can underpin the generation of more complex catalytic networks as introduced above. Carbon fixation involves the reductive formation of organic compounds, notably carboxylates [48], which provide the first of a family of ligands that can coordinate to, and modify, the reactivity of the metal ions present. Re- duction of carbon-containing species results in the concomitant oxidation of the iron sulfide: