BioCosmos Feed

Higher Permeability of l-Ribose Versus d-Ribose through Prebiotically-Relevant Lipid Bilayers Measured by Molecular Dynamics Simulations Challenges Origin of Life Models for the Generation of D-RNA

Tue, 18 Aug 2026 00:00:00 GMT

Membrane permeability has been suggested as a contributing factor in the prebiotic selection of d-ribose as the sugar component of nucleic acid polymers. Experimental work has demonstrated that d-ribose permeates through fatty acid bilayers faster than several diastereomers, but permeation of the enantiomer l-ribose was not experimentally tested. Here, we used molecular dynamics simulations to calculate the permeability coefficients of β-d-ribopyranose and three aldopentose stereoisomers through fatty acid bilayers of varying length and composition, including two bilayers specifically composed to mimic the range of short chain amphiphiles assumed to be present in prebiotic scenarios. The permeation rate of aldopentose stereoisomers through oleic acid bilayers, myristoleic acid bilayers, and 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayers, correlates with experimental permeability measurements. In these three bilayers, β-d-ribopyranose and β-l-ribopyranose permeated similarly. By contrast, in short chain bilayers containing mixtures of lauric acid, myristic acid, and myristoleic acid, β-l-ribopyranose diffused across the membrane between 2-fold and 3-fold faster than β-d-ribopyranose. The rate of intramolecular hydrogen bonding interactions formed during permeation was similar between the two enantiomers. These results imply that the interior of protocells likely contained both enantiomers of ribose and assembled a mixture of heterochiral and homochiral nucleic acid polymers, which would slow down replication and greatly increase consumption of nucleotides. Thus, passive membrane permeation alone cannot select for β-d-ribopyranose in putative prebiotic models, and that competition by β-l-ribopyranose for inclusion in early nucleic acid polymers must be considered in models of protocell evolution.

The RNA World Hypothesis: A Critical Reassessment of Prebiotic Plausibility

Sat, 16 May 2026 00:00:00 GMT

The RNA world hypothesis (RWH) proposes that life originated from self-replicating RNA molecules, yet its prebiotic plausibility remains poorly quantified. This study applies equilibrium thermodynamics to evaluate maximum achievable concentrations of abiotic RNA oligomers in aqueous solution. The free energy of phosphodiester hydrolysis (ΔG°hyd = −22.2 kJ/mol) indicates an equilibrium constant K ≈ 1.3 × 10−4 for nucleotide condensation at 25°C and pH 7. Analysis of prebiotic nucleotide synthesis reveals significant chemical constraints: (1) ribose from formose reactions requires contradictory conditions (pH ~10–12, 60°C–80°C) incompatible with nucleobase formation from HCN polymerization (pH < 7, <0°C); (2) prebiotic phosphate availability was <10−7 M due to mineral sequestration; (3) N-glycosidic bond formation exhibits prohibitively high activation energy; (4) successfully formed molecules and bonds are too unstable on a prebiotic timescale to permit accumulation: ribose t½ ≈ 300 days at 25°C; RNA phosphodiester t½ ≈ 4 years/bond (a 1000-nt RNA has t½, strand ≈ 4 years/999 ≈ 1.5 days). Assuming unrealistically high nucleotide concentrations of 10−10 M—comparable to amino acid estimates—yields tetranucleotide (N4) concentration [N4] ≈ 10−52 M, seven orders of magnitude below the concentration corresponding to one molecule in Earth's total water (10−45 M). Strategies to increase local oligomer concentration through wet-dry cycles or montmorillonite catalysis require experimentally optimized conditions (e.g. pure 10–15 mM activated nucleotides, precise pH 2.5–3, 80°C–90°C) that are prebiotically implausible. Additionally, D-ribose exists as five equilibrating isomers with four potential glycosidic bond sites per isomer, generating ~180–300 mononucleotide isomers and >107 dinucleotide variants, diluting functional sequences exponentially with chain length. These thermodynamic and kinetic constraints indicate that even short RNA oligomers (>3 nucleotides) most probably did not accumulate prebiotically at detectable concentrations, challenging the hypothesis that an RNA World bridged prebiotic chemistry to deoxyribonucleotide hydrolysis (DNA)-based life.

Shared Pathways to Peptides in Biochemistry and Prebiotic Chemistry through Ester Amide Exchange Chemistry

Thu, 30 Apr 2026 00:00:00 GMT

The origin of life requires plausible pathways for the emergence of polymers under realistic early-Earth conditions. Increasing geological and geochemical evidence supports highly dynamic environments characterized by strong temperature gradients and fluctuating hydration states that repeatedly drive chemistry out of equilibrium. Wet–dry cycling in shallow settings can promote polymer formation by favoring condensation during dehydration and hydrolysis during rehydration, thereby imposing a rudimentary, persistence-based selection pressure. Here we highlight a conceptual chemical bridge between prebiotic polymer chemistry and extant biochemistry: ester-mediated amide formation via ester-amide exchange. In modern translation, peptide bond formation proceeds not by direct condensation of amino acids but by nucleophilic attack of the α-amine of the A-site aminoacyl-tRNA on the ester linkage of the P-site peptidyl-tRNA at the ribosomal peptidyl transferase center. Strikingly similar chemistry arises abiotically under wet–dry cycling in mixtures of hydroxy acids and amino acids, where dehydration readily generates esters that subsequently undergo ester-amide exchange to form depsipeptides, which are oligomers composed of mixed ester and amide linkages, without sophisticated catalysts. We argue that wet-dry cycling and ester-mediated exchange may outline a plausible continuum from non-coded depsipeptide formation to the refined ribosomal peptide synthesis, offering an experimentally tractable framework for interrogating the constraints that shaped early polymer evolution.

Dr. Walt Shaw, 1939–2026

Sat, 21 Mar 2026 00:00:00 GMT

On Evolutionary Novelty

Fri, 30 Jan 2026 00:00:00 GMT

Darwin's ‘endless forms most beautiful’ was his testimony to the creative power of natural selection. Creativity, by definition, implies novelty: bringing into existence something which had never before existed. Novelty constitutes the grist for the mill of natural selection to refine those endless forms most beautiful. But whence evolutionary novelty? Since the rise of the Neodarwinian idea of gene selectionism, evolutionary novelty is supposed to arise through new presentation of selective environments and gene modification, reflecting Darwin's own ambition of creating a naturalistic explanation for the generation of his ‘endless forms most beautiful’. The Neodarwinian idea deprives organisms of their fundamental agency of purposefulness and intentionality, which are regarded as illusions rather than fundamental to life itself. Surprisingly, those fundamental attributes arise naturally from the thermodynamics of life combined with a proper understanding of the phenomenon of homeostasis. Adaptation as a purposeful phenomenon driven by organismal intelligence and self-knowledge emerges naturally from this, as well as a new perspective on the evolutionary origins of novel forms and functions.

Assembly Theory Provides A Measure of Specified Complexity That Quantifies but does Not Explain Selection and Evolution

Sun, 26 Oct 2025 00:00:00 GMT

Categorizing complex objects into ‘life’ and ‘not-life’ buckets is hard. Understanding how the ‘life’ objects came to be in the first place is even harder. The authors of assembly theory (AT) purport to make headway on both issues by providing a measure, dubbed assembly, for categorizing objects and a related mechanism, dubbed selection, underlying their discovery. We show that assembly is a measure of specified complexity, leveraging the assembly index ai for the complexity of the object and the copy number ni for its specification. This provides a theoretical foundation for AT’s success as an object-categorizer. AT’s model for selection yields some helpful parameterizations, but lacks concreteness, and does not grapple with the confounding factors that make the problem of life’s origin so challenging. At best, AT’s selection model highlights the actual problem that a viable selection process must address: the problem of information.

Life from Chemistry: A Critical Commentary on the State of Abiogenesis Research

Fri, 12 Sep 2025 00:00:00 GMT

There is No Paradox of Evolution: A Reply to Feser

Fri, 18 Jul 2025 00:00:00 GMT

Edward Feser, in his recent paper ‘Life, Reproduction, and the Paradox of Evolution’, argues that reproduction cannot be explained by natural selection, and as a result is irreducibly teleological. And further, since definitions of life depend on the concept of reproduction, the definition of life is irreducibly teleological as well. It will be argued here that Feser does not make his case. At issue is the absence of an appropriate distinction between “replicability” and “reproduction”. Natural selection can, then, explain reproduction, as reproduction is just selected-for replicability.

Thermodynamic Limitations on the Natural Emergence of Long Chain Molecules: Implications for Origin of Life

Wed, 09 Jul 2025 00:00:00 GMT

For a polymer of N-monomer-units long, or N-mer, which has a dimer decay time constant of τ, the polymer decay time constant is proved to be closely approximated by τ/N (under rather general assumptions). The implications of this for abiogenesis are profound, namely that there would be small amounts of time available (order of days) for a prebiotic sequence of a condensation polymer to serve as the primary information-bearing code for the last universal common ancestor. All three classes of prebiotically relevant polymers (polynucleotides, polypeptides and polysaccharides) are condensation polymers expected to be subject to these time constraints.

Reframing Cancer through a Processual Ontology

Wed, 07 May 2025 00:00:00 GMT

Cancer research has long been dominated by a gene-centric, substantialist ontology that reduces the disease to static mutations, overlooking its dynamic, relational nature. This letter proposes a processual ontology, inspired by Alfred North Whitehead’s philosophy, to reframe cancer as a system of interactions across genetic, epigenetic, and environmental scales. Evidence highlights non-genetic plasticity in resistance, tissue context in tumor behavior, and ancient survival programs in cancer’s origins. Shifting to this perspective fosters holistic research and adaptive therapies, offering a more comprehensive understanding of cancer’s complexity and promising improved outcomes beyond traditional models.

What ‘Has Life Potentially’?

Thu, 24 Apr 2025 00:00:00 GMT

The origin of life in the cosmos poses some perplexing philosophical problems. For instance: Does life exist at the very beginning of the cosmos, or does it emerge at a specific moment that occurs later in the earth's natural history?

Introduction: The Definition of Life

Thu, 24 Apr 2025 00:00:00 GMT

In this special issue of BioCosmos, we address the problem of the definition of life. If we assume that biology is a genuine science, with its own distinctive subject matter, then there must be a real distinction between living and non-living things. We are concerned not merely with the meaning of the word ‘life’ or with merely clarifying our biological concepts, but with uncovering what it is (if anything) in the world that unifies the domain of living things and separates it from the rest of the cosmos. Six distinguished philosophers have contributed their answers to this problem.

Aristotle's Many Lives

Thu, 24 Apr 2025 00:00:00 GMT

Distinctively, Aristotle denies that there is a univocal definition of life, but he still offers an account of how the many different ways of being alive are related. In particular, more advanced forms of life potentially contain less advanced forms of life in them. In this paper, I defend this interpretation of Aristotle against other recent interpreters. I also set out Aristotle's account of the most general life-activity – nutrition – and show how his account doesn't fall prey to the objection that it is parochial.

The Maximum Genetic Diversity Theory: A Comprehensive Framework for Understanding Evolutionary Processes

Thu, 24 Apr 2025 00:00:00 GMT

A good understanding of evolutionary processes is essential for addressing a variety of important scientific questions. In the early 1960s, the discovery of protein sequences revealed an unexpected phenomenon known as genetic equidistance, which led to the development of the molecular clock hypothesis. This hypothesis later inspired Kimura's neutral theory (NT). While the NT has served as a useful null model, it has struggled to fully explain genetic diversity. Systematic neutrality tests of the human mitochondrial genome have raised questions about the validity of the NT. As the molecular clock has fallen out of favor, this has also affected the standing of the NT and reintroduced the genetic equidistance phenomenon (GEP) as an unresolved issue. In the early 2000s, renewed interest in this phenomenon led to the formulation of the maximum genetic diversity (MGD) hypothesis, which offers a more comprehensive approach to understanding evolution. Analytical tests suggest that current genetic distances are primarily at maximum saturation rather than steadily increasing, as previously proposed by the molecular clock and NT. The MGD theory posits that macroevolution – from simple to complex organisms – involves a punctuated rise in epigenetic complexity accompanied by a decrease in the maximum genetic diversity a taxon can sustain. This theory has undergone extensive testing, contributing to our evolving understanding of evolutionary processes.

Life, Reproduction, and the Paradox of Evolution

Sat, 08 Mar 2025 00:00:00 GMT

A neglected but challenging argument developed by Peter Geach, John Haldane, and Stephen Rothman purports to show that reproduction cannot be explained by natural selection and is irreducibly teleological. Meanwhile, the most plausible definitions of life include reproduction as a constitutive feature. The implication of combining these ideas is that life cannot be explained by natural selection and is irreducibly teleological. This does not entail that life cannot be explained in evolutionary terms of some kind, but it does lend support to the controversial view of Jerry Fodor and Thomas Nagel that evolutionists need to look beyond the constraints of Neo-Darwinism.

An Aristotelian-Thomistic Discussion of the Definition of Life

Sat, 08 Mar 2025 00:00:00 GMT

Many deny or doubt that life can be defined.

The Meaning of ‘Life’

Sat, 08 Mar 2025 00:00:00 GMT

Attempts to define life have been uniformly unsuccessful, and this paper argues that no such definition is to be expected. However, it is important that life is not, as is still often assumed, a collection of discrete individual things, but rather a set of deeply intertwined processes. The paper provides three reasons for this view: that living systems are metabolic systems far from thermodynamic equilibrium; that they have characteristic life cycles, often passing through very different states; and that they are typically symbiotic, mutually interdependent with other systems. Recognition of this processual character of life makes clear why an adequate definition of life, a set of necessary and sufficient conditions for being alive, is unlikely to be forthcoming.

What is Life? An Operational Definition

Sat, 08 Mar 2025 00:00:00 GMT

One way of defining life is via a real definition, which gives the essence of life. Another approach is an operational definition, which shows how living things can be tested or measured in a way that is distinctive of the biological. Although I give a real definition elsewhere, in this paper I provide an operational definition, echoing Canguilhem’s dictum that life is what is capable of making mistakes. Biological mistakes are central to the behaviour of organisms, their parts and sub-systems, and the collections to which they belong. I provide an informal definition of a biological mistake. I contrast mistakes with mere failures and malfunctions. Although closely related phenomena, each is distinct. After giving some brief examples of mistake-making and how it can be tested, I reply to some objections to the very idea of a biological mistake.

Structural Bioinformatics Studies of Integral Transmembrane Enzymes pMMO Complex, C560, CYB, and DHSD and their AlphaFold3-Predicted Water-Soluble QTY Variants

Tue, 28 Jan 2025 00:00:00 GMT

The QTY (glutamine, threonine, tyrosine) code is a simple protein engineering and design tool that systematically replaces the hydrophobic amino acids leucine (L), isoleucine (I), valine (V), and phenylalanine (F) into the hydrophilic amino acids glutamine (Q), threonine (T), and tyrosine (Y), respectively, to enable the water-solubility of membrane proteins including membrane enzymes. In this study, we present the structural bioinformatics study of six membrane protein enzymes with experimentally determined CryoEM structures including the methane monooxygenase pMMO complex (pMOA, pMOB, pMOC), CYB, C560, DHSD, and their AlphaFold3-predicted water-soluble QTY variants. We applied the QTY code only to the transmembrane alpha-helices of the proteins. We then superposed structures of CryoEM-determined native proteins with their water-soluble QTY variants. The QTY code engineered water-soluble QTY variants demonstrate remarkable structural similarity with their native structures, with RMSD (Root Mean Square Deviation) values between 0.506Å and 0.887Å despite significant (33.33–86.61%) changes to the protein sequence of the transmembrane domains. To verify the effectiveness of our study, we show the changes in hydrophobicity surfaces between the native proteins and their QTY variants, and explain the rationale behind such change. Our structural bioinformatics studies provide key insight into differences between the hydrophobic alpha-helices and alpha-hydrophilic helices. The QTY code will likely further aid the future applications of methane oxidation enzymes. The water-soluble QTY variants could aid in studying and utilization of the enzymes in aqueous environments without detergent solubilization and stabilization. These QTY variant membrane enzymes may be particularly useful for future industrial-scale production in aqueous chassis such as filamentous algae.

The Complexity of Glycan Structures, Functions, and Origins

Tue, 31 Dec 2024 00:00:00 GMT

Sugars have more reactive groups than either amino acids or nucleotides. This allows them to form branched oligo- and polysaccharides. Therefore, the number of possible structures is far greater than comparably sized peptides or nucleic acids. The result is that carbohydrates have far greater information-carrying potential than either proteins or nucleic acids. Carbohydrates are present in, and essential for, all three of life’s kingdom’s; archaea, bacteria, and eukaryotes. This article illustrates the structural, functional, and evolutionary complexity of animal carbohydrates, i.e. glycans. These glycans include glycosaminoglycans, glycolipids, and glycoproteins. Attachment of glycans to proteins increases their functional range and allows their functions to be fine-tuned in response to the environment. Different copies of a single protein have different glycans attached. Each copy is a glycoform and the combination of a protein’s glycoforms is called its glycotype. Protein glycotypes are cell-, tissue- and developmentally-specific. The combination glycoproteins, glycosaminoglycans, and glycolipids form glycopatterns that are essential for organization of cells into tissues during development. The synthesis of a single glycan structure requires numerous enzymes, and the production of the necessary functional protein glycotypes and cellular glycopatterns requires integrated regulated expression of these enzymes by (glyco)gene regulatory networks (gGRNs) and micro RNA (miRNA) regulatory networks. Explanations for the origin of glycans must include mechanisms for the origin of glycosyl transferases, hydrolases, metabolic pathways for the activated sugar precursors, and all the components and information necessary to form the aforementioned regulatory networks. The challenges that this poses for a standard neo-Darwinian explanation are discussed.