SEARCH · bioRxiv Science

Results for “Biochemistry”

Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 757 records · Page 42Linked to original sources

bioRxiv2025

Joint multi-omics profiling of brain and body health in aging

The human brain and peripheral systems undergo coordinated changes throughout the lifespan, yet studies of aging have traditionally examined these systems as separate entities. Here we ask how brain health relates to peripheral biomarkers of bodily health including body mass index, blood pressure, and blood biochemistry results. We use partial least squares analysis to identify generalizable patterns of covariance between multi-modal neuroimaging data (structural, functional, diffusion, and arterial spin labeling MRI), demographic, and peripheral physiological markers in two large-scale deeply phenotyped datasets: the Human Connectome Project-Aging and UK Biobank. This data-driven pattern learning approach identifies two principal axes of brain-body associations in both biological sex groups. The first axis is driven by the dominant contribution of age. Across multiple brain measures, aging is associated with loss of brain structural integrity and cerebral vascular dysfunction. The second axis is driven by metabolic features, characterized by low high-density lipoprotein cholesterol, elevated body mass index, blood pressure, glycosylated hemoglobin, insulin, glucose, and alanine aminotransferase, and reduced cerebral blood perfusion. Finally, we show that deviations from a healthy metabolic profile are linked to cognitive deficits, particularly in females. Our study contributes to development of comprehensive translatable biomarkers for brain health assessment, and highlights the importance of metabolic health as a determinant of brain health.

neuroscience↗

bioRxiv2025

Asymmetry in hydrophobicity induces electric potential in non-charged protein condensates

The capacity of biomolecular condensates to establish and modulate electrochemical equilibria is emerging as an important functioning mechanism in cellular biochemistry. However, the physical chemistry basis of the electric potentials arising from biomacromolecular phase transitions remains unclear. Here, we show that asymmetry in hydrophobicity, which is a generalizable feature in condensate system, can directly encode an electric potential gradient between the dilute and the dense phases. We demonstrate that using a non-charged intrinsically disordered protein, ion-dependent kosmotropic effect can encode measurable pH and interphase potential gradients into condensate. All-atom molecular dynamics simulations further reveal that the distinct intrinsic transfer free energy of ions defines the ion partitioning capability of condensates via favorable interactions with protein backbones. The simulation also shows the existence of both interfacial and interphase electric potentials. These built-in potentials modulate the partitioning and reactivity of charged solutes, enabling non-enzymatic, potential-dependent chemistry within condensates. Our findings identify hydrophobic asymmetry as a simple and generalizable mechanism for charging biological matter, linking water activity and ion energetics to the emergent electrochemistry of condensates.

biophysics↗

bioRxiv2025

Anthropogenic nitrogen deposition decouples relationships with decomposing microbes, altering SOM molecular composition, but not molecular complexity or diversity

Soil organic matter (SOM) consists of diverse biochemical constituents, spanning a spectrum of chemical complexity, and the relative abundance of these substrates influences microbial metabolism and soil carbon persistence. However, mechanistic controls governing these processes and how they may be affected by environmental change remains incomplete. This study aims to assess (1) the molecular-level changes that occur across stages of root decomposition, from undecayed plant root litter to 1-year decomposed root litter, to mineral SOM and (2) how these changes are altered by anthropogenic nitrogen (N) deposition by using SOM biochemical and microbiome datasets and a long-term field experiment. N deposition did not significantly alter undecomposed or 1-year decomposed root litter, but did alter decomposing microbial communities and mineral SOM biochemical composition, specifically in lignin- and lipid-derived compounds. Taken together, this restructuring of microbial communities and alteration of SOM biochemistry likely contributed to the previously observed reduction in SOM decomposition.

ecology↗

bioRxiv2025

Phase separation as a tunable regulator of canonical gene regulatory motifs

Gene regulatory networks govern essential cellular processes such as signal transduction, metabolism, and cell fate control. Within these networks, canonical motifs such as genetic toggle switches and repressilators serve as building blocks that generate bistable and oscillatory behaviors. An open question is how cells regulate the dynamical behavior of such motifs, both in natural contexts and in synthetic systems. Recent studies highlight phase separation of transcription factors (TFs) and nucleic acids as a key organizing principle of intracellular biochemistry. In this work, we explore how phase separation of TFs influences the dynamics of toggle switch and repressilator using mean-field theory and stochastic simulations. Our mean-field analysis reveals that phase separation reshapes motif dynamics by altering fixed-point stability and basin geometry in toggle switch, and by altering oscillatory cycles in repressilator. A key finding for both motifs is that when multiple TFs undergo phase separation, the one with the lowest saturation concentration for phase separation dominates system dynamics. Interestingly, stochastic simulations show that the impact of phase separation on fluctuations (or noise) in the abundance of transcription factors within network motifs is architecture-dependent and sharply contrasts with its buffering effect on noise in the expression of isolated genes. Overall, our results show that biomolecular phase separation acts as a physical principle for tuning stability and noise in gene regulatory networks, providing new insights into cellular decision-making.

biophysics↗

bioRxiv2025

The dynamic response of the bacterial flagellar motor to its direct intracellular input signal

The bacterial flagellar motor drives bacterial swimming and chemotaxis by rotating helical flagellar filaments. When Escherichia coli navigates chemical gradients, the motor switches from counterclockwise (CCW) during forward swimming to clockwise (CW) during direction-changing tumbles. The motor responds indirectly to extracellular chemosensory input to membrane-bound chemoreceptors using an intervening intracellular signaling pathway. How the motor responds to its direct input signal - the diffusible messenger CheY-P - remains poorly understood. Steady-state motor measurements have been modeled as an allosteric switch between CCW/CW states that depend on mean CheY-P levels. Allosteric models have suggested that as many as 20 CheY-P molecules can be bound to the motor when it switches rotational direction. But steady-state models cannot predict the sensitivity of the motor to dynamic changes in CheY-P that essentially modulate chemotactic behavior. We present an optogenetic reagent that precisely controls the direct dynamical input signal to the motor. We designed a "caged" molecule, Opto-CheY, that is transiently activated by photon absorption. We find that activation and binding of 1-3 CheY-P molecules is sufficient to switch the motor from the CCW to CW state. The sensitivity of the motor to small changes in CheY-P occupancy helps resolve a long-standing paradox about the high sensitivity of the chemotactic response to external sensory input. Optogenetic biochemistry by light-activated uncaging of signal molecules is a new strategy to dissect information-processing in the living cell. Significance StatementMotile bacteria swim to better environments by modulating the rotation of the bacterial flagellar motor. How this motor responds to intracellular signaling activity is poorly understood. The physiologically-relevant response of the motor is to transient activation of intracellular signaling molecules on the sub-second time scale of bacterial decision-making. Here, we report the first optogenetic probe that targets in vivo the output module of the the chemotactic network. We demonstrate that the motor has high dynamical sensitivity to the binding of single intracellular signaling molecules. This solves a long-standing problem of high sensitivity and signal amplification in the bacterial chemotactic response.

biophysics↗

bioRxiv2025

Sphingolipid-driven interleaflet coupling orchestrates Rho-GTPase recruitment to nanodomains for signal activation in plants

Biological membranes are both laterally heterogeneous and asymmetrical across leaflets, yet how this asymmetry contributes to signal transduction remains unclear. Here we show that sphingolipid-driven interleaflet coupling coordinates nanodomain organization and Rho-GTPase activation in plants. Using molecular dynamics simulations, super-resolution and single-molecule imaging, quantitative genetics, and biochemistry, we find that very long acyl chain (VLCFA)-containing sphingolipids in the outer leaflet interdigitate with phosphatidylserine (PS) in the inner leaflet, forming a vertical molecular bridge that organizes PS into nanodomains. This coupling promotes recruitment and activation of the Rho-GTPase ROP6 in response to auxin, whereas disruption of VLCFA synthesis or sphingolipid composition disperses PS and ROP6 nanodomains, impairing cytoskeletal reorganization and directional growth. Our findings reveal interleaflet coupling as a fundamental organizing principle linking membrane asymmetry to signaling, providing a conceptual framework for spatial and temporal control of signal transduction across eukaryotic membranes.

plant biology↗

bioRxiv2025

Biocompatibility assessment of SilkMA-Gelatin ink tuned for 3D extrusion bioprinting

3D bioprinting applications have led to the development of multifunctional scaffolds that are biocompatible, overcoming shear stress to provide structural integrity. We report the isolation of silk fibroin (SF) using calcium chloride (CaCl2), which was further developed into an ink comprising silkMA and gelatin, demonstrating effective cytocompatibility and biocompatibility when 3D printed using an extrusion-based 3D bioprinter. Rheological characterization of SilkMA-Gelatin showed an improved viscosity and printability of the formulation as compared to an unmodified silk-gelatin composition. SilkMA-gelatin was bioprinted with NIH3T3 cells and demonstrated enhanced viability and proliferation, highlighting its cytocompatibility and ability to support a favourable 3D microenvironment. In vivo biocompatibility of the 3D bioprinted SilkMA-Gelatin was evaluated in Wistar rats, where 3D printed scaffolds maintained structural stability for up to 1 month, with no inflammatory response, progressive cell infiltration, and re-epithelialization. Serum biochemistry analysis, including ALP, ALT, LDH, and Urea (BUN), remained within normal physiological ranges, further confirming systemic safety. Based on the findings, the optimized SilkMA-gelatin ink proves to be highly effective in fabricating cell-laden structures that are stable, exhibit enhanced cytocompatibility and biocompatibility, and offer promising potential for advanced tissue regeneration applications. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=172 SRC="FIGDIR/small/687334v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@1fad3dcorg.highwire.dtl.DTLVardef@6b2d3aorg.highwire.dtl.DTLVardef@6655b8org.highwire.dtl.DTLVardef@85d894_HPS_FORMAT_FIGEXP M_FIG Schematic overview of 3D bioprinting in wound healing and biomedical applications C_FIG

bioengineering↗

bioRxiv2025

Enabling regiospecific di-halogenation in one-pot reactions using an engineered single-component flavin-dependent tryptophan halogenase

Installation of halogen atoms to organic compounds through flavin-dependent halogenases (FDHs) catalyzed reactions has emerged as an attractive strategy in organic biochemistry and synthetic biology. A cyanobacterial FDH termed AetF that contains FDH and flavin reductase in the same polypeptide chain could become a useful tool enzyme as the need of including a reductase is omitted. Notably, AetF exploits a unique substrate-interaction network to consecutively brominate tryptophan (Trp) on C5 and then C7 to generate di-brominated Trp. In this study, structure-based engineering is used to eliminate the C7 halogenation capacity of AetF. The resulting variant AetF-AIF that contains three residue substitutions mainly catalyzes bromination or iodination on C5 of Trp. We also show that combining AetF-AIF in tandem with the wild type AetF enables the generation of heterogeneously halogenated Trp in a one-pot reaction. The final products, 5-Br-7-I-Trp or 5-I-7-Br-Trp depending on the addition order of halides, account for a high ratio in the reaction mixture without additional purification step. These results display the potentials of single-component Trp-FDHs in a wide application of the halogenation reactions. Table of Content Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/687318v1_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@101bd34org.highwire.dtl.DTLVardef@12ca797org.highwire.dtl.DTLVardef@aee280org.highwire.dtl.DTLVardef@1984907_HPS_FORMAT_FIGEXP M_FIG A single-component flavin-dependent halogenase that catalyzes di-bromination of tryptophan was engineered as a mono-halogenase and coupled in a one-pot reaction for the synthesis of heterogeneously halogenated tryptophan. C_FIG

molecular biology↗

bioRxiv2025

Learning from All Views: A Multiview Contrastive Framework for Metabolite Annotation

Metabolomics, enabled by high-throughput mass spectrometry, promises to advance our understanding of cellular biochemistry and guide new discoveries in disease mechanisms, drug development, and personalized medicine. However, as the assignment of molecular structures to measured spectra is challenging, annotation rates remain low and hinder potential advancements. We present MultiView Projection (MVP), a novel framework for learning a joint embedding space between molecules and spectra by leveraging multiple data views: molecular graphs, molecular fingerprints, spectra, and consensus spectra. MVP builds on contrastive multiview learning to capture mutual information across views, leading to more robust and generalizable representations for spectral annotation. Unlike prior approaches that consider multiple views via concatenation or as targets of auxiliary tasks, MVP learns from all views jointly, resulting in improved molecular candidate ranking. Notably, MVP supports annotation using either individual spectra or consensus spectra, enabling flexible use of multiple measurements. On the MassSpecGym benchmark, we show that annotation using query consensus spectra significantly outperforms rank aggregation strategies based on constituent spectrum annotation. Using the consensus spectrum view, MVP achieves 35.99% and 13.96% rank@1 when retrieving candidates by mass and formula, respectively. When ranking using individual spectra, MVP demonstrates performance that is superior to or on par with existing methods, achieving 26.37% and 11.10% rank@1 for candidates by mass and formula, respectively. MVP offers a flexible, extensible foundation for learning from multiple molecule/spectra data views. For Table of Contents Only O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/688047v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@f6c219org.highwire.dtl.DTLVardef@40f8d4org.highwire.dtl.DTLVardef@19031b6org.highwire.dtl.DTLVardef@1afa58d_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2025

Biophysical Design Space for Cellular Self-assembly and Dynamics

In natural biological systems, cells organize into tissues through interactions of several processes, including cellular signaling, collective migration, contractile activity of cytoskeletal elements and interactions with their surroundings. In recent decades, advancements in microscopy, genetic engineering, biochemistry, and computational modeling have enabled a more quantitative understanding of these processes. In this article, we present an integrated computational framework that couples various physical mechanisms such as cell-cell adhesion, strength and persistence of cellular motility, and the background stiffness. We use this framework to study how they collectively interact to determine the self-organization of the cells from a pseudo-random structure as well as the migration behavior of the cells. Notably, our simulations predict that motility has a two-way effect on cellular self-assembly: it promotes aggregation at moderate levels but disrupts clusters when excessively strong, yielding an optimal motility for formation of multicellular clusters. On the other hand, adhesion shows a two-stage effect: At lower value it self-assembles the structure, at higher value it compacts it. Furthermore, we experimentally demonstrate the motility-assisted self-aggregation of cells using cancer cells in a granular mechanical milieu. Finally we show that cell-cell adhesion and background medium tune the strength and persistence of cellular migration. Altogether, this work presents a computational framework that allows us to design phase behavior of collective of cells tuning their interaction, motility, and the background mechanics.

biophysics↗

bioRxiv2025

Homogeneous antibody-DNA-conjugates using unmodified oligonucleotides and photo-crosslinkable protein G-HUH endonuclease fusion proteins

Antibody-DNA conjugates are increasingly used in analytical biochemistry and nanotechnology. However, current methods for their preparation often lack specificity, resulting in heterogeneous products. Here, we present a novel strategy to covalently label the Fc domain of antibodies with single-strand DNA in a site-specific and stoichiometrically controlled manner. This method employs unmodified oligonucleotides and a fusion protein consisting of a protein G dimer linked to an HUH endonuclease. We first evaluated the sequence specificity and optimal conditions for DNA attachment to three HUH endonuclease variants, DCV, PCV2, and WDV. Our results show increased sequence specificity in the presence of Mg2+ compared to the more commonly used Mn2+ cofactor ion. Although formation of the phospho-tyrosine bond is found to be reversible, no significant hydrolysis of the protein-DNA conjugates is observed for up to 8 days at room temperature. The DCV domain allowed essentially complete formation of DNA-fusion protein conjugates at a 1:1 protein-DNA ratio, eliminating the need for removal of excess oligos. Subsequent photo-crosslinking yielded antibody-DNA conjugates that were successfully used in a proximity extension assay (PEA) to detect TNF and IL-6. Our method provides an efficient, low cost and generally applicable method to prepare homogeneous antibody-DNA conjugates with 1:1 stoichiometry.

bioengineering↗

bioRxiv2025

Study on Dianthus superbus L. against Acute Liver Injury via the Gut-Liver Axis -- Regulation of Gut Microbiota and Tryptophan Metabolism to Activate AhR Signaling

BackgroundDianthus superbus L. (DS) treats liver diseases, but its ALI mechanism via gut microbiota/metabolites is unclear. PurposeInvestigate DS effects on CCl-induced ALI and mechanisms. MethodsDS components (HPLC-MS/MS) were identified. ALI rats received DS. Liver/colon injury, fibrosis (biochemistry, histology, IHC, IF, WB for -SMA, Collagen I, Occludin, ZO-1), serum metabolomics, fecal 16S rRNA, and tryptophan-targeted metabolomics were assessed. Antibiotics and FMT from DS-treated donors explored microbiota roles. Results37 components, including Kaempferol and Aurantiamide, were identified. DS attenuated ALI, reducing hepatic -SMA/Collagen I while increasing AhR/Cyp1a1, and upregulating colonic Occludin/ZO-1. FMT replicated DS benefits. Untargeted metabolomics linked effects to Linoleic/Tryptophan metabolism. 16S rRNA showed increased beneficial microbiota (HT002, Lactobacillus, Romboutsia); FMT confirmed Lactobacillus enrichment. DS normalized tryptophan metabolites (4-Hydroxybenzoic acid, L-Kynurenine, Indole-3-carboxaldehyde). ConclusionDS ameliorates ALI gut-microbiota-dependently by modulating tryptophan metabolism, enhancing intestinal barrier function, activating AHR signaling, and suppressing fibrosis biomarkers, indicating its potential as a microbiota modulator for ALI. ImportanceAcute liver injury is a serious health threat with limited treatment options. This study explores how a traditional medicinal herb, Dianthus superbus L. (DS), protects the liver through an unexpected route: the gut. We discovered that DS works by rebalancing the community of gut bacteria, which in turn improves the intestinal barrier and fine-tunes the bodys tryptophan metabolism. This cascade of effects ultimately activates a key cellular pathway (AhR) that reduces liver inflammation and fibrosis. Our findings not only clarify how this traditional remedy works but also highlight the critical role of the gut-liver axis, positioning DS as a promising, microbiota-targeting therapeutic candidate for preventing and treating liver disease.

microbiology↗

bioRxiv2025

How do selective serotonin reuptake inhibitors effect metabolism? A lesson for teaching non-majors about enzymes and metabolic pathways

Understanding foundational concepts in molecular biology and biochemistry can be challenging for many college students. For non-science majors, an introductory biology course may be their sole exposure to college-level science and only opportunity to learn about enzymes and metabolism. Framing these topics within issues that are personally relevant can make the material more meaningful and impactful for non-majors. There is a need to develop curricula that instructors of large-enrollment introductory biology courses can use to teach non-biology majors about enzymes and metabolism. Here, we designed and implemented a lesson that integrates enzyme function and metabolism within the context of selective serotonin reuptake inhibitors (SSRIs). SSRIs are a widely prescribed class of antidepressants whose efficacy can be influenced by enzymes. Genetic polymorphisms in the genes encoding these enzymes can result in individual differences in metabolic responses and lead to medication-induced weight gain. Framing the content in this way allows non-major students to connect enzyme function to genetics, energy balance, and metabolic processes through a health-related, societally relevant issue. In our lesson, students engaged in collaborative learning activities that emphasized interpreting biological data, graphing, and scientific reasoning. Pre- and post-assessment data from a conceptual inventory showed learning gains that exceeded baseline data and were greater than those observed with the traditional curriculum. Students also reported a more coherent understanding of enzyme function and a greater appreciation of the contents relevance to their own lives. This lesson provides an example of embedding biochemical concepts in real-world contexts for students who are non-science majors.

scientific communication and education↗

bioRxiv2017

Repetitive DNA reeling by the Cascade-Cas3 complex in nucleotide unwinding steps

CRISPR-Cas loci provide an RNA-guided adaptive immune system against invading genetic elements. Interference in type I systems relies on the RNA-guided surveillance complex Cascade for target DNA recognition and the trans-acting Cas3 helicase/nuclease protein for target degradation. Even though the biochemistry of CRISPR interference has been largely covered, the biophysics of DNA unwinding and coupling of the helicase and nuclease domains of Cas3 remains elusive. Here we employed single-molecule FRET to probe the helicase activity with a high spatiotemporal resolution. We show that Cas3 remains tightly associated with the target-bound Cascade complex while reeling in the target DNA using a spring-loaded mechanism. This spring-loaded reeling occurs in distinct bursts of three base pairs, that each underlie three successive 1-nt unwinding events. Reeling is highly repetitive, compensating for inefficient nicking activity of the nuclease domain. Our study reveals that the discontinuous helicase properties of Cas3 and its tight interaction with Cascade ensure well controlled degradation of target DNA only.

biophysics↗

bioRxiv2017

Application of the immunoregulatory receptor LILRB1 as a novel crystallisation chaperone for class I peptide-MHC complexes

X-ray crystallographic studies of class I peptide-MHC molecules (pMHC) continue to provide important insights into immune recognition, however their success depends on generation of diffraction-quality crystals, which remains a significant challenge. While protein engineering techniques such as surface-entropy reduction and lysine methylation have proven utility in facilitating and/or improving protein crystallisation, they risk affecting the conformation and biochemistry of the class I MHC antigen binding groove. An attractive alternative is the use of noncovalent crystallisation chaperones, however these have not been developed for pMHC. Here we describe a method for promoting class I pMHC crystallisation, by exploiting its natural ligand interaction with the immunoregulatory receptor LILRB1 as a novel crystallisation chaperone. First, focussing on a model HIV-1-derived HLA-A2-restricted peptide, we determined a 2.4[A] HLA-A2/LILRB1 structure, which validated that co-crystallisation with LILRB1 does not alter conformation of the antigenic peptide. We then demonstrated that addition of LILRB1 enhanced the crystallisation of multiple pMHC complexes, and identified a generic condition for initial co-crystallisation. LILRB1 chaperone-based pMHC crystallisation enabled structure determination for class I pMHC previously intransigent to crystallisation, including both conventional and post-translationally-modified peptides, of diverse lengths. LILRB1 chaperone-mediated crystallisation should expedite molecular insights into the immunobiology of diverse immune-related diseases and immunotherapeutic strategies, particularly involving class I pMHC complexes that are challenging to crystallise. Moreover, since the LILRB1 recognition interface involves predominantly non-polymorphic regions of the MHC molecule, the approach we outline could prove applicable to a diverse range of class I pMHC.

immunology↗

bioRxiv2017

Evolutionary plasticity in the innate immune function of Akirin

Eukaryotic gene expression requires the coordinated action of transcription factors, chromatin remodelling complexes and RNA polymerase. The conserved nuclear protein Akirin plays a central role in immune gene expression in insects and mammals, linking the SWI/SNF chromatin-remodelling complex with the transcription factor NF{kappa}B. Although nematodes lack NF{kappa}B, Akirin is also indispensable for the expression of defence genes in the epidermis of Caenorhabditis elegans following natural fungal infection. Through a combination of reverse genetics and biochemistry, we discovered that in C. elegans Akirin has conserved its role of bridging chromatin-remodellers and transcription factors, but that the identity of its functional partners is different since it forms a physical complex with NuRD proteins and the POU-class transcription factor CEH-18. In addition to providing a substantial step forward in our understanding of innate immune gene regulation in C. elegans, our results give insight into the molecular evolution of lineage-specific signalling pathways.

immunology↗

bioRxiv2017

Metals enable a non-enzymatic acetyl CoA pathway

The evolutionary origins of carbon fixation, the biological conversion of CO2 to metabolites, remain unclear. Phylogenetics indicates that the AcCoA pathway, the reductive fixation of CO2 to acetyl and pyruvate, was a key biosynthetic route used by the Last Universal Common Ancestor (LUCA) to build its biochemistry. However, debate exists over whether CO2 fixation is a relatively late invention of pre-LUCA evolution or whether it dates back to prebiotic chemistry. Here we show that zero-valent forms of the transition metals known to act as co-factors in the AcCoA pathway (Fe0, Ni0, Co0) fix CO2 on their surface in a manner closely resembling the biological pathway, producing acetate and pyruvate in near mM concentrations following cleavage from the surface. The reaction is robust over a wide range of temperatures and pressures with acetate and pyruvate constituting the major products in solution at 1 bar of CO2 and 30 {degrees}g;C. The discovered conditions also promote 7 of the 11 steps of the rTCA cycle and amino acid synthesis, providing a stunning direct connection between simple inorganic chemistry and ancient CO2-fixation pathways. The results strongly sup-port the notion that CO2-fixation pathways are an outgrowth of spontaneous geochemistry.

evolutionary biology↗

bioRxiv2017

Firefly genomes illuminate the origin and evolution of bioluminescence

Fireflies are among the best-studied of the bioluminescent organisms. Despite longterm interest in the biochemistry, neurobiology, and evolution of firefly flash signals and the widespread biotechnological applications of firefly luciferase, only a limited set of genes related to this complex trait have been described. To investigate the genetic basis of firefly bioluminescence, we generated a high-quality reference genome for the Big Dipper firefly Photinus pyralis, from which the first laboratory luciferase was cloned, using long-read (PacBio), short-read (Illumina), and Hi-C sequencing technologies. To facilitate comparative genomics, we also generated short-read genome assemblies for a Japanese firefly Aquatica lateralis and a bioluminescent click beetle, Ignelater luminosus. Analyses of these genomic datasets supports at least two independent gains of luminescence in beetles, and provides new insights into the evolution of beetle bioluminescence and chemical defenses that likely co-evolved over their 100 million years of evolution.

genomics↗