The Emergence and Early Evolution of Biological Carbon-Fixation

The fixation of into living matter sustains all life on Earth, and embeds the biosphere within geochemistry. The six known chemical pathways used by extant organisms for this function are recognized to have overlaps, but their evolution is incompletely understood. Here we reconstruct the complete early evolutionary history of biological carbon-fixation, relating all modern pathways to a single ancestral form. We find that innovations in carbon-fixation were the foundation for most major early divergences in the tree of life. These findings are based on a novel method that fully integrates metabolic and phylogenetic constraints. Comparing gene-profiles across the metabolic cores of deep-branching organisms and requiring that they are capable of synthesizing all their biomass components leads to the surprising conclusion that the most common form for deep-branching autotrophic carbon-fixation combines two disconnected sub-networks, each supplying carbon to distinct biomass components. One of these is a linear folate-based pathway of reduction previously only recognized as a fixation route in the complete Wood-Ljungdahl pathway, but which more generally may exclude the final step of synthesizing acetyl-CoA. Using metabolic constraints we then reconstruct a “phylometabolic” tree with a high degree of parsimony that traces the evolution of complete carbon-fixation pathways, and has a clear structure down to the root. This tree requires few instances of lateral gene transfer or convergence, and instead suggests a simple evolutionary dynamic in which all divergences have primary environmental causes. Energy optimization and oxygen toxicity are the two strongest forces of selection. The root of this tree combines the reductive citric acid cycle and the Wood-Ljungdahl pathway into a single connected network. This linked network lacks the selective optimization of modern fixation pathways but its redundancy leads to a more robust topology, making it more plausible than any modern pathway as a primitive universal ancestral form

The compositional and evolutionary logic of metabolism

Metabolism displays striking and robust regularities in the forms of modularity and hierarchy, whose composition may be compactly described. This renders metabolic architecture comprehensible as a system, and suggests the order in which layers of that system emerged. Metabolism also serves as the foundation in other hierarchies, at least up to cellular integration including bioenergetics and molecular replication, and trophic ecology. The recapitulation of patterns first seen in metabolism, in these higher levels, suggests metabolism as a source of causation or constraint on many forms of organization in the biosphere. We identify as modules widely reused subsets of chemicals, reactions, or functions, each with a conserved internal structure. At the small molecule substrate level, module boundaries are generally associated with the most complex reaction mechanisms and the most conserved enzymes. Cofactors form a structurally and functionally distinctive control layer over the small-molecule substrate. Complex cofactors are often used at module boundaries of the substrate level, while simpler ones participate in widely used reactions. Cofactor functions thus act as "keys" that incorporate classes of organic reactions within biochemistry. The same modules that organize the compositional diversity of metabolism are argued to have governed long-term evolution. Early evolution of core metabolism, especially carbon-fixation, appears to have required few innovations among a small number of conserved modules, to produce adaptations to simple biogeochemical changes of environment. We demonstrate these features of metabolism at several levels of hierarchy, beginning with the small-molecule substrate and network architecture, continuing with cofactors and key conserved reactions, and culminating in the aggregation of multiple diverse physical and biochemical processes in cells.Comment: 56 pages, 28 figure

Remnants of an ancient metabolism without phosphate

Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility. We used systems biology approaches to explore the alternative hypothesis that a protometabolism could have emerged prior to the incorporation of phosphate. Surprisingly, we identified a cryptic phosphate-independent core metabolism producible from simple prebiotic compounds. This network is predicted to support the biosynthesis of a broad category of key biomolecules. Its enrichment for enzymes utilizing iron-sulfur clusters, and the fact that thermodynamic bottlenecks are more readily overcome by thioester rather than phosphate couplings, suggest that this network may constitute a "metabolic fossil" of an early phosphate-free nonenzymatic biochemistry. Our results corroborate and expand previous proposals that a putative thioester-based metabolism could have predated the incorporation of phosphate and an RNA-based genetic system. PAPERCLIP

Environmental boundary conditions for the origin of life converge to an organo-sulfur metabolism

Published in final edited form as: Nat Ecol Evol. 2019 December ; 3(12): 1715–1724. doi:10.1038/s41559-019-1018-8.It has been suggested that a deep memory of early life is hidden in the architecture of metabolic networks, whose reactions could have been catalyzed by small molecules or minerals before genetically encoded enzymes. A major challenge in unravelling these early steps is assessing the plausibility of a connected, thermodynamically consistent proto-metabolism under different geochemical conditions, which are still surrounded by high uncertainty. Here we combine network-based algorithms with physico-chemical constraints on chemical reaction networks to systematically show how different combinations of parameters (temperature, pH, redox potential and availability of molecular precursors) could have affected the evolution of a proto-metabolism. Our analysis of possible trajectories indicates that a subset of boundary conditions converges to an organo-sulfur-based proto-metabolic network fuelled by a thioester- and redox-driven variant of the reductive tricarboxylic acid cycle that is capable of producing lipids and keto acids. Surprisingly, environmental sources of fixed nitrogen and low-potential electron donors are not necessary for the earliest phases of biochemical evolution. We use one of these networks to build a steady-state dynamical metabolic model of a protocell, and find that different combinations of carbon sources and electron donors can support the continuous production of a minimal ancient 'biomass' composed of putative early biopolymers and fatty acids.80NSSC17K0295 - Intramural NASA; 80NSSC17K0296 - Intramural NASA; T32 GM100842 - NIGMS NIH HHSAccepted manuscrip

The Role of N2 as a Geo-Biosignature for the Detection and Characterization of Earth-like Habitats

Since the Archean, N2 has been a major atmospheric constituent in Earth's atmosphere. Nitrogen is an essential element in the building blocks of life, therefore the geobiological nitrogen cycle is a fundamental factor in the long term evolution of both Earth and Earth-like exoplanets. We discuss the development of the Earth's N2 atmosphere since the planet's formation and its relation with the geobiological cycle. Then we suggest atmospheric evolution scenarios and their possible interaction with life forms: firstly, for a stagnant-lid anoxic world, secondly for a tectonically active anoxic world, and thirdly for an oxidized tectonically active world. Furthermore, we discuss a possible demise of present Earth's biosphere and its effects on the atmosphere. Since life forms are the most efficient means for recycling deposited nitrogen back into the atmosphere nowadays, they sustain its surface partial pressure at high levels. Also, the simultaneous presence of significant N2 and O2 is chemically incompatible in an atmosphere over geological timescales. Thus, we argue that an N2-dominated atmosphere in combination with O2 on Earth-like planets within circumstellar habitable zones can be considered as a geo-biosignature. Terrestrial planets with such atmospheres will have an operating tectonic regime connected with an aerobe biosphere, whereas other scenarios in most cases end up with a CO2-dominated atmosphere. We conclude with implications for the search for life on Earth-like exoplanets inside the habitable zones of M to K-stars

Modern views of ancient metabolic networks

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

Atmospheric Evolution

Earth's atmosphere has evolved as volatile species cycle between the atmosphere, ocean, biomass and the solid Earth. The geochemical, biological and astrophysical processes that control atmospheric evolution are reviewed from an "Earth Systems" perspective, with a view not only to understanding the history of Earth, but also to generalizing to other solar system planets and exoplanets.Comment: 34 pages, 3 figures, 2 tables. Accepted as a chapter in "Encyclopaedia of Geochemistry", Editor Bill White, Springer-Nature, 201

Modeling pN2 through Geological Time: Implications for Planetary Climates and Atmospheric Biosignatures

Nitrogen is a major nutrient for all life on Earth and could plausibly play a similar role in extraterrestrial biospheres. The major reservoir of nitrogen at Earth's surface is atmospheric N2, but recent studies have proposed that the size of this reservoir may have fluctuated significantly over the course of Earth's history with particularly low levels in the Neoarchean - presumably as a result of biological activity. We used a biogeochemical box model to test which conditions are necessary to cause large swings in atmospheric N2 pressure. Parameters for our model are constrained by observations of modern Earth and reconstructions of biomass burial and oxidative weathering in deep time. A 1-D climate model was used to model potential effects on atmospheric climate. In a second set of tests, we perturbed our box model to investigate which parameters have the greatest impact on the evolution of atmospheric pN2 and consider possible implications for nitrogen cycling on other planets. Our results suggest that (a) a high rate of biomass burial would have been needed in the Archean to draw down atmospheric pN2 to less than half modern levels, (b) the resulting effect on temperature could probably have been compensated by increasing solar luminosity and a mild increase in pCO2, and (c) atmospheric oxygenation could have initiated a stepwise pN2 rebound through oxidative weathering. In general, life appears to be necessary for significant atmospheric pN2 swings on Earth-like planets. Our results further support the idea that an exoplanetary atmosphere rich in both N2 and O2 is a signature of an oxygen-producing biosphere.Comment: 33 pages, 11 figures, 2 tables (includes appendix), published in Astrobiolog

The thermodynamic landscape of carbon redox biochemistry

Redox biochemistry plays a key role in the transduction of chemical energy in all living systems. Observed redox reactions in metabolic networks represent only a minuscule fraction of the space of all possible redox reactions. Here we ask what distinguishes observed, natural redox biochemistry from the space of all possible redox reactions between natural and non-natural compounds. We generate the set of all possible biochemical redox reactions involving linear chain molecules with a fixed numbers of carbon atoms. Using cheminformatics and quantum chemistry tools we analyze the physicochemical and thermodynamic properties of natural and non-natural compounds and reactions. We find that among all compounds, aldose sugars are the ones with the highest possible number of connections (reductions and oxidations) to other molecules. Natural metabolites are significantly enriched in carboxylic acid functional groups and depleted in carbonyls, and have significantly higher solubilities than non-natural compounds. Upon constructing a thermodynamic landscape for the full set of reactions as a function of pH and of steady-state redox cofactor potential, we find that, over this whole range of conditions, natural metabolites have significantly lower energies than the non-natural compounds. For the set of 4-carbon compounds, we generate a Pourbaix phase diagram to determine which metabolites are local energetic minima in the landscape as a function of pH and redox potential. Our results suggest that, across a set of conditions, succinate and butyrate are local minima and would thus tend to accumulate at equilibrium. Our work suggests that metabolic compounds could have been selected for thermodynamic stability, and yields insight into thermodynamic and design principles governing nature’s metabolic redox reactions.https://www.biorxiv.org/content/10.1101/245811v1Othe