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Cuevas, B.

Publications and source records attributed to Cuevas, B..

4 recordsLinked to original sources

Agnostic Tools for Life Detection: A Multiscale Approach to Biological and Chemical Reaction Networks

Life manifests itself across a variety of different operative scales, ranging from molecular networks up to ecologies. Deep conceptual difficulties arise when trying to define exactly what lifes distinguishing attributes are, and how they may be quantitatively distinguished from abiotic systems that are complicated but demonstrably not alive. Here we assembled different biotic and abiotic chemical reaction networks to test whether network-level (macroscale) and reaction-level (microscale) metrics can impartially distinguish biotic from abiotic category networks. Macroscale attributes such as statistical tests for a discrete networks heavy-tailed connectivity distribution generally distinguish bona fide biotic and protobiotic networks (E. coli heterotrophy, pruned protometabolism, KEGG) from abiotic networks but with two significant exceptions (radiolytic network and the Open Reaction Database). Microscale attributes such as an analysis of the frequency of a set of six primitive reaction motifs shows a depletion of some motifs in all chemical networks and the prevalence of others in specific networks; all networks were readily distinguishable from random network variants across all motifs. A comparison of the chemical spaces spanned by the different networks points to similarity and dissimilarity relationships between networks. Independent component analysis of an aggregate of all measured attributes, across all contexts, reliably distinguishes abiotic, prebiotic and biotic networks from one another. The combination of macro- and microscale attributes forms an agnostic toolset that may help to evaluate the prebiotic plausibility of different candidate settings for the origins of life, and may inform new ways of detecting and recognizing living systems (engineered or extraterrestrial) that differ from Terran biochemistry.

systems biology↗

ChemOrigins: A community curated database for origins of life chemistry

The origin of life is one of the most compelling questions in science. While experimental prebiotic chemistry has produced a wide range of reactions and plausible pathways, the resulting data remain fragmented across numerous publications and disciplinary journals. Here, we introduce ChemOrigins, an open-access, community-curated knowledge graph that organizes experimentally supported prebiotic reactions. By representing molecules, reactions, conditions, and literature sources as interconnected nodes, ChemOrigins enables modular grouping of reactions and supports complex, query-driven exploration via a graph database architecture. We demonstrate the utility of this framework through text-based searches, reaction network expansions, and the interactive visualization of user-annotated chemical modules. Unlike generative models, ChemOrigins prioritizes curated, evidence-based content and fosters community contributions through expert annotations and a user-friendly interface. As a structured resource, ChemOrigins is designed to complement existing chemical databases and serve as a foundation for computational, educational, and theoretical research in the origins-of-life field.

bioinformatics↗

Nitrogenase structural evolution across Earth s history

Life on Earth is about 4 billion years old--nearly as old as the planet itself. Over this immense timespan, living systems and their biomolecules have both adapted to and driven profound changes in the Earths environment. Among these, certain critical enzymes emerged early and have persisted through planetary extremes. Here, we implement an integrated approach to investigate the structural evolution of nitrogenase, an ancient and globally essential enzyme responsible for biological nitrogen fixation. Despite the ecological diversity of its host microbes, nitrogenase retains strict functional constraints, including extreme oxygen sensitivity, high energy demands, and substrate availability. We combined phylogenetics, ancestral sequence reconstruction, protein crystallography and deep-learning based structural prediction to resurrect nearly three billion years of nitrogenase structural history. This effort represents the first effort to predict the full set of extant and ancestral structures along the evolutionary tree of a single enzyme, yielding over 5000 structural models. Our framework lays a foundation for reconstructing key structural constraints that shape protein evolution and examining ancient enzymes within the broader context of phylogenetic relationships and environmental transitions across geological timescales.

evolutionary biology↗

Ancestral structure prediction reveals the conformational impact of the RuBisCO small subunit across time

Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is an ancient protein critical for CO2-fixation and global biogeochemistry. Form-I RuBisCO complexes uniquely harbor small subunits that form a hexadecameric complex together with their large subunits. The small subunit protein is thought to have significantly contributed to RuBisCOs response to the atmospheric rise of O2 [~]2.5 billion years ago, marking a pivotal point in the enzymes evolutionary history. Here, we performed a comprehensive evolutionary analysis of extant and ancestral RuBisCO sequences and structures to explore the impact of the small subunits earliest integration on the molecular dynamics of the overall complex. Our simulations suggest that the small subunit restricted the conformational flexibility of the large subunit early in its history, impacting the evolutionary trajectory of the Form-I RuBisCO complex. Molecular dynamics investigations of CO2 and O2 gas distribution around predicted ancient RuBisCO complexes suggest that a proposed "CO2 reservoir" role for the small subunit is not conserved throughout the enzymes evolutionary history. The evolutionary and biophysical response of RuBisCO to changing atmospheric conditions on ancient Earth showcase multi-level and trackable responses of enzymes to environmental shifts over long timescales.

evolutionary biology↗