The Divergence and Natural Selection of Autocatalytic Primordial Metabolic Systems

The diversity of the central metabolism of modern organisms is caused by the existence of a few metabolic modules, combination of which produces multiple metabolic pathways. This paper analyzes biomimetically reconstructed coupled autocatalytic cycles as the basis of ancestral metabolic systems. The mechanism for natural selection and evolution in autocatalytic chemical systems may be affected by natural homeostatic parameters such as ambient chemical potentials, temperature, and pressure. Competition between separate parts of an autocatalytic network with positive-plus-negative feedback resulted in the formation of primordial autotrophic, mixotrophic, and heterotrophic metabolic systems. This work examined the last common ancestor of a set of coupled metabolic cycles in a population of protocells. Physical-chemical properties of these cycles determined the main principles of natural selection for the ancestral Bacteria and Archaea taxa.     

Cycles and the Qualitative Evolution of Chemical Systems

Cycles are abundant in most kinds of networks, especially in biological ones. Here, we investigate their role in the evolution of a chemical reaction system from one self-sustaining composition of molecular species to another and their influence on the stability of these compositions. While it is accepted that, from a topological standpoint, they enhance network robustness, the consequence of cycles to the dynamics are not well understood. In a former study, we developed a necessary criterion for the existence of a fixed point, which is purely based on topological properties of the network. The structures of interest we identified were a generalization of closed autocatalytic sets, called chemical organizations. Here, we show that the existence of these chemical organizations and therefore steady states is linked to the existence of cycles. Importantly, we provide a criterion for a qualitative transition, namely a transition from one self-sustaining set of molecular species to another via the introduction of a cycle. Because results purely based on topology do not yield sufficient conditions for dynamic properties, e.g. stability, other tools must be employed, such as analysis via ordinary differential equations. Hence, we study a special case, namely a particular type of reflexive autocatalytic network. Applications for this can be found in nature, and we give a detailed account of the mitotic spindle assembly and spindle position checkpoints. From our analysis, we conclude that the positive feedback provided by these networks'' cycles ensures the existence of a stable positive fixed point. Additionally, we use a genome-scale network model of the Escherichia coli sugar metabolism to illustrate our findings. In summary, our results suggest that the qualitative evolution of chemical systems requires the addition and elimination of cycles.     

Signatures of Arithmetic Simplicity in Metabolic Network Architecture

Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life''s origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that properties similar to those predicted for the artificial chemistry hold also for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity.     

Distribution of protein poly(ADP-ribosyl)ation systems across all domains of life

Poly(ADP-ribosyl)ation is a post-translational modification of proteins involved in regulation of many cellular pathways. Poly(ADP-ribose) (PAR) consists of chains of repeating ADP-ribose nucleotide units and is synthesized by the family of enzymes called poly(ADP-ribose) polymerases (PARPs). This modification can be removed by the hydrolytic action of poly(ADP-ribose) glycohydrolase (PARG) and ADP-ribosylhydrolase 3 (ARH3). Hydrolytic activity of macrodomain proteins (MacroD1, MacroD2 and TARG1) is responsible for the removal of terminal ADP-ribose unit and for complete reversion of protein ADP-ribosylation.Poly(ADP-ribosyl)ation is widely utilized in eukaryotes and PARPs are present in representatives from all six major eukaryotic supergroups, with only a small number of eukaryotic species that do not possess PARP genes. The last common ancestor of all eukaryotes possessed at least five types of PARP proteins that include both mono and poly(ADP-ribosyl) transferases. Distribution of PARGs strictly follows the distribution of PARP proteins in eukaryotic species. At least one of the macrodomain proteins that hydrolyse terminal ADP-ribose is also always present. Therefore, we can presume that the last common ancestor of all eukaryotes possessed a fully functional and reversible PAR metabolism and that PAR signalling provided the conditions essential for survival of the ancestral eukaryote in its ancient environment.PARP proteins are far less prevalent in bacteria and were probably gained through horizontal gene transfer. Only eleven bacterial species possess all proteins essential for a functional PAR metabolism, although it is not known whether PAR metabolism is truly functional in bacteria. Several dsDNA viruses also possess PARP homologues, while no PARP proteins have been identified in any archaeal genome.Our analysis of the distribution of enzymes involved in PAR metabolism provides insight into the evolution of these important signalling systems, as well as providing the basis for selection of the appropriate genetic model organisms to study the physiology of the specific human PARP proteins.     

Respiratory Chains in the Last Common Ancestor of Living Organisms

Sequences in current databases show that a number of proteins involved in respiratory processes are homologous in archaeal and bacterial species. In particular, terminal oxidases belonging to oxygen, nitrate, sulfate, and sulfur respiratory pathways have been sequenced in members of both domains. They include cytochrome oxidase, nitrate reductase, adenylylsulfate reductase, sulfite reductase, and polysulfide reductase. These proteins can be assigned to the last common ancestor of living organisms assuming that the deepest split of the three domains of life occurred between Archaea and Bacteria and that they were not acquired through lateral gene transfer by one of these domains. These molecular data indicate that several of the most important respiratory pathways arose early in evolution and that the last common ancestor of living organisms was not a simple organism in its energetic metabolism. Rather, it may have been able to gain energy by means of at least four electron transport chains, and therefore it may have been prepared to face a wide range of environmental conditions.     

Compositional complementarity and prebiotic ecology in the origin of life

We hypothesize that life began not with the first self-reproducing molecule or metabolic network, but as a prebiotic ecology of co-evolving populations of macromolecular aggregates (composomes). Each composome species had a particular molecular composition resulting from molecular complementarity among environmentally available prebiotic compounds. Natural selection acted on composomal species that varied in properties and functions such as stability, catalysis, fission, fusion and selective accumulation of molecules from solution. Fission permitted molecular replication based on composition rather than linear structure, while fusion created composomal variability. Catalytic functions provided additional chemical novelty resulting eventually in autocatalytic and mutually catalytic networks within composomal species. Composomal autocatalysis and interdependence allowed the Darwinian co-evolution of content and control (metabolism). The existence of chemical interfaces within complex composomes created linear templates upon which self-reproducing molecules (such as RNA) could be synthesized, permitting the evolution of informational replication by molecular templating. Mathematical and experimental tests are proposed.     

Computational identification of obligatorily autocatalytic replicators embedded in metabolic networks

Background  

If chemical A is necessary for the synthesis of more chemical A, then A has the power of replication (such systems are known as autocatalytic systems). We provide the first systems-level analysis searching for small-molecular autocatalytic components in the metabolisms of diverse organisms, including an inferred minimal metabolism.     

The natural selection of metabolism explains curvature in allometric scaling

I simulate the natural selection of metabolism and mass to explain the curvature in the metabolic allometry for placental and marsupial mammals. The simulation model starts with a single ancestor in each clade at the Cretaceous–Palaeogene boundary 65 million years ago. The release of inter‐specific competition by the extinction of dinosaurs make it possible for each clade to diversify into a multitude of species across a wide range of empty niches. The selection of mass in these species depends on the net assimilated energy that depends on 1) the handling of the resources in the different niches, and on 2) mass‐specific metabolism that defines the pace of the handling process. The model is fitted to explain the maximum observed body masses over time and the current inter‐specific allometry for metabolism. The selection of mass‐specific metabolism is found to bend the metabolic allometry over time, even when all species have the same selection on the per‐generation time‐scale of natural selection. This is because the smaller species evolve over a larger number of generations than the larger species. The strongest curvature is in the placental clade, where the estimated rate of exponential increase in mass‐specific metabolism is 9.3 × 10^?9 (95% CI: 7.3 × 10^?9 – 1.1 × 10^?8) on the per‐generation time‐scale. This is an order of magnitude larger than the estimate for marsupials, in agreement with an average metabolism that is 30% larger in placentals relative to marsupials of similar size.     

Group II introns: structure, folding and splicing mechanism

Group II introns are large autocatalytic RNAs found in organellar genomes of plants and lower eukaryotes, as well as in some bacterial genomes. Interestingly, these ribozymes share characteristic traits with both spliceosomal introns and non-LTR retrotransposons and may have a common evolutionary ancestor. Furthermore, group II intron features such as structure, folding and catalytic mechanism differ considerably from those of other large ribozymes, making group II introns an attractive model system to gain novel insights into RNA biology and biochemistry. This review explores recent advances in the structural and mechanistic characterization of group II intron architecture and self-splicing.     

Shifts in growth strategies reflect tradeoffs in cellular economics

The growth rate‐dependent regulation of cell size, ribosomal content, and metabolic efficiency follows a common pattern in unicellular organisms: with increasing growth rates, cell size and ribosomal content increase and a shift to energetically inefficient metabolism takes place. The latter two phenomena are also observed in fast growing tumour cells and cell lines. These patterns suggest a fundamental principle of design. In biology such designs can often be understood as the result of the optimization of fitness. Here we show that in basic models of self‐replicating systems these patterns are the consequence of maximizing the growth rate. Whereas most models of cellular growth consider a part of physiology, for instance only metabolism, the approach presented here integrates several subsystems to a complete self‐replicating system. Such models can yield fundamentally different optimal strategies. In particular, it is shown how the shift in metabolic efficiency originates from a tradeoff between investments in enzyme synthesis and metabolic yields for alternative catabolic pathways. The models elucidate how the optimization of growth by natural selection shapes growth strategies.     

Physico-chemical and evolutionary constraints for the formation and selection of first biopolymers: towards the consensus paradigm of the abiogenic origin of life

During the last two decades, the common school of thought has split into two, so that the problem of the origin of life is tackled in the framework of either the 'replication first' paradigm or the 'metabolism first' scenario. The first paradigm suggests that the life started from the spontaneous emergence of the first, supposedly RNA-based 'replicators' and considers in much detail their further evolution in the so-called 'RNA world'. The alternative hypothesis of 'metabolism first' derives the life from increasingly complex autocatalytic chemical cycles. In this work, we emphasize the role of selection during the pre-biological stages of evolution and focus on the constraints that are imposed by physical, chemical, and biological laws. We try to demonstrate that the 'replication first' and 'metabolism first' hypotheses complement, rather than contradict, each other. We suggest that life on Earth has started from a 'metabolism-driven replication'; the suggested scenario might serve as a consensus scheme in the framework of which the molecular details of origin of life can be further elaborated. The key feature of the scenario is the participation of the UV irradiation both as driving and selecting forces during the earlier stages of evolution.     

Transitional forms between the three domains of life and evolutionary implications

The question as to the origin and relationship between the three domains of life is lodged in a phylogenetic impasse. The dominant paradigm is to see the three domains as separated. However, the recently characterized bacterial species have suggested continuity between the three domains. Here, we review the evidence in support of this hypothesis and evaluate the implications for and against the models of the origin of the three domains of life. The existence of intermediate steps between the three domains discards the need for fusion to explain eukaryogenesis and suggests that the last universal common ancestor was complex. We propose a scenario in which the ancestor of the current bacterial Planctomycetes, Verrucomicrobiae and Chlamydiae superphylum was related to the last archaeal and eukaryotic common ancestor, thus providing a way out of the phylogenetic impasse.     

Selection between multiple periodic regimes in a biochemical system: complex dynamic behaviour resolved by use of one-dimensional maps

We analyse a model biochemical system in which two autocatalytic enzyme reactions are coupled in series, in conditions where multiple stable periodic regimes coexist for the same set of parameter values. We determine how the periodic regimes are reached from different initial conditions. The structure of the attraction basins is generally simple in the case of two coexisting limit cycles (birhythmicity). This structure and the associated behaviour may, however, become highly complex. In particular, the system exhibits enhanced sensitivity to initial conditions when the boundaries of the attraction basins are fractal. In the latter case, it becomes difficult to predict the evolution towards either one of two limit cycles, a phenomenon known as final state sensitivity. We show how these complex phenomena can be explained in a unified and simple manner by means of one-dimensional return maps derived from the time evolution of the model and from fifth degree polynomial equations. We suggest experimental tests of the sensitivity to initial conditions in chemical systems presenting birhythmicity. The physiological significance of the results is discussed with respect to the sensitivity of regulatory systems admitting multiple stable biological rhythms.     

Population growth of human Y chromosomes: a study of Y chromosome microsatellites

We use variation at a set of eight human Y chromosome microsatellite loci to investigate the demographic history of the Y chromosome. Instead of assuming a population of constant size, as in most of the previous work on the Y chromosome, we consider a model which permits a period of recent population growth. We show that for most of the populations in our sample this model fits the data far better than a model with no growth. We estimate the demographic parameters of this model for each population and also the time to the most recent common ancestor. Since there is some uncertainty about the details of the microsatellite mutation process, we consider several plausible mutation schemes and estimate the variance in mutation size simultaneously with the demographic parameters of interest. Our finding of a recent common ancestor (probably in the last 120,000 years), coupled with a strong signal of demographic expansion in all populations, suggests either a recent human expansion from a small ancestral population, or natural selection acting on the Y chromosome.     

Biochemistry and Evolution of Anaerobic Energy Metabolism in Eukaryotes

Summary: Major insights into the phylogenetic distribution, biochemistry, and evolutionary significance of organelles involved in ATP synthesis (energy metabolism) in eukaryotes that thrive in anaerobic environments for all or part of their life cycles have accrued in recent years. All known eukaryotic groups possess an organelle of mitochondrial origin, mapping the origin of mitochondria to the eukaryotic common ancestor, and genome sequence data are rapidly accumulating for eukaryotes that possess anaerobic mitochondria, hydrogenosomes, or mitosomes. Here we review the available biochemical data on the enzymes and pathways that eukaryotes use in anaerobic energy metabolism and summarize the metabolic end products that they generate in their anaerobic habitats, focusing on the biochemical roles that their mitochondria play in anaerobic ATP synthesis. We present metabolic maps of compartmentalized energy metabolism for 16 well-studied species. There are currently no enzymes of core anaerobic energy metabolism that are specific to any of the six eukaryotic supergroup lineages; genes present in one supergroup are also found in at least one other supergroup. The gene distribution across lineages thus reflects the presence of anaerobic energy metabolism in the eukaryote common ancestor and differential loss during the specialization of some lineages to oxic niches, just as oxphos capabilities have been differentially lost in specialization to anoxic niches and the parasitic life-style. Some facultative anaerobes have retained both aerobic and anaerobic pathways. Diversified eukaryotic lineages have retained the same enzymes of anaerobic ATP synthesis, in line with geochemical data indicating low environmental oxygen levels while eukaryotes arose and diversified.     

Organizational invariance and metabolic closure: analysis in terms of (M,R) systems

This article analyses the work of Robert Rosen on an interpretation of metabolic networks that he called (M,R) systems. His main contribution was an attempt to prove that metabolic closure (or metabolic circularity) could be explained in purely formal terms, but his work remains very obscure and we try to clarify his line of thought. In particular, we clarify the algebraic formulation of (M,R) systems in terms of mappings and sets of mappings, which is grounded in the metaphor of metabolism as a mathematical mapping. We define Rosen's central result as the mathematical expression in which metabolism appears as a mapping f that is the solution to a fixed-point functional equation. Crucially, our analysis reveals the nature of the mapping, and shows that to have a solution the set of admissible functions representing a metabolism must be drastically smaller than Rosen's own analysis suggested that it needed to be. For the first time, we provide a mathematical example of an (M,R) system with organizational invariance, and we analyse a minimal (three-step) autocatalytic set in the context of (M,R) systems. In addition, by extending Rosen's construction, we show how one might generate self-referential objects f with the remarkable property f(f)=f, where f acts in turn as function, argument and result. We conclude that Rosen's insight, although not yet in an easily workable form, represents a valuable tool for understanding metabolic networks.     

Self-maintenance and self-reproduction in an abstract cell model

Living cells must maintain their membranes by active metabolism. The membrane is not static but a dynamic structure that has evolved along with its internal reactions. When we reflect on the emergence and evolution of primitive cells, we should not forget the mutual dependency between membranes and metabolic cycles inside the cell. In this paper, we present a simple abstract model of the self-maintaining cell. A metabolic cycle will produce a self-assembling membrane that will enclose the metabolic cycle. We show that a self-maintaining cell has the potential to reproduce itself spontaneously. Further, we have demonstrated two different ways of cellular reproduction depending on the mobility of chemicals. In the first case, a cell releases autocatalytic chemicals that create new cells outside the mother cell. In the second case, a cell grows larger and divides itself into daughter cells by creating a new internal dividing membrane.     

The natural selection of metabolism and mass selects lifeforms from viruses to multicellular animals

I show that the natural selection of metabolism and mass can select for the major life‐history and allometric transitions that define lifeforms from viruses, over prokaryotes and larger unicells, to multicellular animals. The proposed selection is driven by a mass‐specific metabolism that is selected as the pace of the resource handling that generates net energy for self‐replication. An initial selection of mass is given by a dependence of mass‐specific metabolism on mass in replicators that are close to a lower size limit. A sublinear maximum dependence selects for virus‐like replicators, with no intrinsic metabolism, no cell, and practically no mass. A superlinear dependence selects for prokaryote‐like self‐replicating cells, with asexual reproduction and incomplete metabolic pathways. These self‐replicators have selection for increased net energy, and this generates a gradual unfolding of population‐dynamic feed‐back selection from interactive competition. The incomplete feed‐back selects for larger unicells with more developed metabolic pathways, and the completely developed feed‐back for multicellular animals with sexual reproduction. This model unifies the natural selection of lifeforms from viruses to multicellular animals, and it provides a parsimonious explanation where allometries and major life histories evolve from the natural selection of metabolism and mass.     

Host Adaptation in Legionellales Is 1.9 Ga,Coincident with Eukaryogenesis

Bacteria adapting to living in a host cell caused the most salient events in the evolution of eukaryotes, namely the seminal fusion with an archaeon, and the emergence of both mitochondrion and chloroplast. A bacterial clade that may hold the key to understanding these events is the deep-branching gammaproteobacterial order Legionellales—containing among others Coxiella and Legionella—of which all known members grow inside eukaryotic cells. Here, by analyzing 35 novel Legionellales genomes mainly acquired through metagenomics, we show that this group is much more diverse than previously thought, and that key host-adaptation events took place very early in its evolution. Crucial virulence factors like the Type IVB secretion (Dot/Icm) system and two shared effector proteins were gained in the last Legionellales common ancestor (LLCA). Many metabolic gene families were lost in LLCA and its immediate descendants, including functions directly and indirectly related to molybdenum metabolism. On the other hand, genome sizes increased in the ancestors of the Legionella genus. We estimate that LLCA lived approximately 1.89 Ga, probably predating the last eukaryotic common ancestor by approximately 0.4–1.0 Gy. These elements strongly indicate that host adaptation arose only once in Legionellales, and that these bacteria were using advanced molecular machinery to exploit and manipulate host cells early in eukaryogenesis.