Jordana Cepelewicz, The Math That Tells Cells What They Are , , 2019 pp. 1-7.
During development, cells seem to decode their fate through optimal information processing, which could hint at a more general principle of life. Cells in embryos need to make their way across a “developmental landscape” to their eventual fate. New findings bear on how they may do this so efficiently.
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M Polo Camacho, What’s all the fuss about? The inheritance of acquired traits is compatible with the Central Dogma, History And Philosophy Of The Life Sciences, 2020 pp. 1-15.
The Central Dogma of molecular biology, which holds that DNA makes protein and not the other way around, is as influential as it is controversial. Some believe the Dogma has outlived its usefulness, either because it fails to fully capture the ins-and-outs of protein synthesis (Griffiths and Stotz in Genetics and philosophy Cambridge introductions to philosophy and biology, Cambridge University Press, Cambridge, 2013; Stotz in Hist Philos Life Sci 28(4):533–548, 2006), because it turns on a confused notion of information (Sarkar in Molecular models of life, MIT Press, Cambridge, 2004), or because it problematically assumes the unidirectional flow of information from DNA to protein (Gottlieb, in: Oyama, Griffiths, Gray (eds), Cycles of contingency: developmental systems and evolution, MIT Press, Cam- bridge, 2001). This paper evaluates an underexplored defense of the Dogma, which relies on the assumption that the Dogma and the Inheritance of Acquired Traits, a principle which dates as far back as Jean Baptiste-Lamarck, are incompatible prin- ciples (Smith in The theory of evolution, Cambridge University Press, Cambridge, 1993; Judson in The eighth day of creation, Jonathan Cape, London, 1979; Dawkins in The extended phenotype, Oxford University Press, Oxford, 1970; Cobb in PLoS Biol 15(9):e2003243, 2017. https://doi.org/10.1371/journal.pbio.2003243; Wilkins in BioEssays 24(10):960–973, 2002. https://doi.org/10.1002/bies.10167; Graur The fallacious commingling of two unrelated hypotheses: ‘the central dogma’ and ‘dna makes rna makes protein’. Judge Starling., 2018. http://judgestarling.tumblr.com/ post/177554581856/the-fallacious-commingling-of-two-unrelated). By appealing to empirical evidence in molecular science, I argue that this apparent incompatibility is indeed merely apparent. I conclude by briefly demonstrating how these considera- tions bear on the topic of conceptual pluralism in the philosophy of science (Stencel and Proszewska in Found Sci 23(4):603–620, 2018. https://doi.org/10.1007/s1069 9-017-9543-x; Lu and Bourrat in Br J Philos Sci 69(3):775–800, 2018. https://doi. org/10.1093/bjps/axx019).
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A L Drăgoi, On the very low probability of complex life forms to be just emergent phenomena and about the “continuous” versus “intermittent” free will, Philosophia Naturalis, .
Page 1. 1 On the very low probability of complex life forms to be just emergent phenomena and about the “continuous” versus “intermittent” free will * DOI: Article version: 1.0 (no matter this current paper version, its latest variant …
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Jingxian Duan et al., The cell-wide web coordinates cellular processes by directing site-specific Ca2+ flux across cytoplasmic nanocourses, Nature Communications, 2019 pp. 1-12.
Ca2+ coordinates diverse cellular processes, yet how function-specific signals arise is enig- matic. We describe a cell-wide network of distinct cytoplasmic nanocourses with the nucleus at its centre, demarcated by sarcoplasmic reticulum (SR) junctions (≤400 nm across) that restrict Ca2+ diffusion and by nanocourse-specific Ca2+-pumps that facilitate signal segre- gation. Ryanodine receptor subtype 1 (RyR1) supports relaxation of arterial myocytes by unloading Ca2+ into peripheral nanocourses delimited by plasmalemma-SR junctions, fed by sarco/endoplasmic reticulum Ca2+ ATPase 2b (SERCA2b). Conversely, stimulus-specified increases in Ca2+ flux through RyR2/3 clusters selects for rapid propagation of Ca2+ signals throughout deeper extraperinuclear nanocourses and thus myocyte contraction. Nuclear envelope invaginations incorporating SERCA1 in their outer nuclear membranes demarcate further diverse networks of cytoplasmic nanocourses that receive Ca2+ signals through discrete RyR1 clusters, impacting gene expression through epigenetic marks segregated by their associated invaginations. Critically, this circuit is not hardwired and remodels for dif- ferent outputs during cell proliferation.
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Jean-Pierre Eckmann et al., Colloquium: Proteins: The physics of amorphous evolving matter, Reviews Of Modern Physics, 2019 vol. 91 (3) p. 031001.
Protein is matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with diverse biochemistry. But it is also a point along an evolutionary trajectory determined by the function performed by the protein within a hierarchy of interwoven interaction networks of the cell, the organism, and the population. A physical theory of proteins therefore needs to unify both aspects, the biophysical and the evolutionary. Specifically, it should provide a model of how the DNA gene is mapped into the functional phenotype of the protein. Several physical approaches to the protein problem are reviewed, focusing on a mechanical framework which treats proteins as evolvable condensed matter: Mutations introduce localized perturbations in the gene, which are translated to localized perturbations in the protein matter. A natural tool to examine how mutations shape the phenotype are Green’s functions. They map the evolutionary linkage among mutations in the gene (termed epistasis) to cooperative physical interactions among the amino acids in the protein. The mechanistic view can be applied to examine basic questions of protein evolution and design.
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Jeroen Eyckmans et al., A Hitchhiker's Guide to Mechanobiology, Developmental Cell, 21 (2011) 35-47.
More than a century ago, it was proposed that mechanical forces could drive tissue formation. However, only recently with the advent of enabling biophysical and molecular technologies are we beginning to understand how individual cells transduce mechanical force into biochemical signals. In turn, this knowledge of mechanotransduction at the cellular level is beginning to clarify the role of mechanics in patterning processes during embryonic development. In this perspective, we will discuss current mechanotransduction paradigms, along with the technologies that have shaped the field of mechanobiology.
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Devon M Fitzgerald and Susan M Rosenberg, What is mutation? A chapter in the series: How microbes “jeopardize” the modern synthesis, Plos Genetics, 15 (2019) e1007995-14.
Mutations drive evolution and were assumed to occur by chance: constantly, gradually, roughly uniformly in genomes, and without regard to environmental inputs, but this view is being revised by discoveries of molecular mechanisms of mutation in bacteria, now trans- lated across the tree of life. These mechanisms reveal a picture of highly regulated muta- genesis, up-regulated temporally by stress responses and activated when cells/organisms are maladapted to their environments—when stressed—potentially accelerating adaptation. Mutation is also nonrandom in genomic space, with multiple simultaneous mutations falling in local clusters, which may allow concerted evolution—the multiple changes needed to adapt protein functions and protein machines encoded by linked genes. Molecular mecha- nisms of stress-inducible mutation change ideas about evolution and suggest different ways to model and address cancer development, infectious disease, and evolution generally.
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B R Frieden and R A Gatenby, Signal transmission through elements of the cytoskeleton form an optimized information network in eukaryotic cells, Scientific Reports, 2019 pp. 1-10.
Multiple prior empirical and theoretical studies have demonstrated wire-like flow of electrons and ions along elements of the cytoskeleton but this has never been linked to a biological function. Here we propose that eukaryotes use this mode of signal transmission to convey spatial and temporal environmental information from the cell membrane to the nucleus. the cell membrane, as the interface between intra- and extra-cellular environments, is the site at which much external information is received. prior studies have demonstrated that transmembrane ion gradients permit information acquisition when an environmental signal interacts with specialized protein gates in membrane ion channels and producing specific ions to flow into or out of the cell along concentration gradients. The resulting localized change in cytoplasmic ion concentrations and charge density can alter location and enzymatic function of peripheral membrane proteins. this allows the cell to process the information and rapidly deploy a local response. Here we investigate transmission of information received and processed in and around the cell membrane by elements of the cytoskeleton to the nucleus to alter gene expression. We demonstrate signal transmission by ion flow along the cytoskeleton is highly optimized. In particular, microtubules, with diameters of about 30 nm, carry coarse-grained Shannon information to the centrosome adjacent to the nucleus with minimum loss of input source information. And, microfilaments, with diameters of about 4 nm, transmit maximum Fisher (fine-grained) information to protein complexes in the nuclear membrane. these previously unrecognized information dynamics allow continuous integration of spatial and temporal environmental signals with inherited information in the genome.
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Rosa D Hernansaiz-Ballesteros et al., Single molecules can operate as primitive biological sensors, switches and oscillators, , 2018 pp. 1-14.
Background: Switch-like and oscillatory dynamical systems are widely observed in biology. We investigate the simplest biological switch that is composed of a single molecule that can be autocatalytically converted between two opposing activity forms. We test how this simple network can keep its switching behaviour under perturbations in the system.
Results: We show that this molecule can work as a robust bistable system, even for alterations in the reactions that drive the switching between various conformations. We propose that this single molecule system could work as a primitive biological sensor and show by steady state analysis of a mathematical model of the system that it could switch between possible states for changes in environmental signals. Particularly, we show that a single molecule phosphorylation-dephosphorylation switch could work as a nucleotide or energy sensor. We also notice that a given set of reductions in the reaction network can lead to the emergence of oscillatory behaviour.
Conclusions: We propose that evolution could have converted this switch into a single molecule oscillator, which could have been used as a primitive timekeeper. We discuss how the structure of the simplest known circadian clock regulatory system, found in cyanobacteria, resembles the proposed single molecule oscillator. Besides, we speculate if such minimal systems could have existed in an RNA world.
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Antony M Jose, A framework for parsing heritable information, Journal Of The Royal Society Interface, 17 (2020) 20200154-10.
Living systems transmit heritable information using the replicating gene sequences and the cycling regulators assembled around gene sequences. Here, I develop a framework for heredity and development that includes the cycling regulators parsed in terms of what an organism can sense about itself and its environment by defining entities, their sensors and the sensed properties. Entities include small molecules (ATP, ions, metabolites, etc.), macromolecules (individual proteins, RNAs, polysaccharides, etc.) and assemblies of molecules. While concentration may be the only relevant property measured by sensors for small molecules, multiple properties that include concentration, sequence, conformation and modification may all be measured for macromolecules and assemblies. Each configuration of these entities and sensors that is recreated in successive generations in a given environment thus specifies a potentially vast amount of information driving complex development in each generation. This entity–sensor–property framework explains how sensors limit the number of distinguishable states, how distinct molecular configurations can be functionally equivalent and how regulation of sensors prevents detection of some perturbations. Overall, this framework is a useful guide for understanding how life evolves and how the storage of information has itself evolved with complexity since before the origin of life.
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Michael Lynch and Bogi Trickovic, A Theoretical Framework for Evolutionary Cell Biology, Journal Of Molecular Biology, 2020 pp. 1-33.
One of the last uncharted territories in evolutionary biology concerns the link with cell biology. Because all phenotypes ultimately derive from events at the cellular level, this connection is essential to building a mechanism- based theory of evolution. Given the impressive developments in cell biological methodologies at the structural and functional levels, the potential for rapid progress is great. The primary challenge for theory development is the establishment of a quantitative framework that transcends species boundaries. Two approaches to the problem are presented here: establishing the long-term steady-state distribution of mean phenotypes under specific regimes of mutation, selection, and drift; and evaluating the energetic costs of cellular structures and functions. Although not meant to be the final word, these theoretical platforms harbor potential for generating insight into a diversity of unsolved problems, ranging from genome structure to cellular architecture to aspects of motility in organisms across the Tree of Life.
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Osvaldo A Martin and Jorge A Vila, The Marginal Stability of Proteins: How Jiggling and Wiggling of Atoms are Connected to Neutral Evolution, Arxiv.Org, 2019 1907.07524v1, q-bio.BM.
Experimental evidence indicates that proteins are marginally stable. Unlike all previous proposals here we suggest, on a statistical thermodynamics basis, that the upper bound of the marginal stability of proteins also belongs to biomacromolecular complexes and its origin should be sought on fluctuations of the pairwise and many-body interactions on both the macro-molecules and the solvent. In other words, at the global minimum of the free energy all folding dominant forces are almost compensated in a state of quasi-equilibrium where the structures preserve their biological activity. Thus, mutations disrupting this equilibrium beyond the protein marginal stability upper bound (7.4 kcal/mol) will be subject to negative selection and mutations that preserve it will be neutral or nearly neutral, with respect to the marginal stability. Although, proteins can still evolve under the influence of natural selection.
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Johnjoe McFadden and Jim Al-Khalili, The origins of quantum biology, Proceedings Of The Royal Society A: Mathematical, Physical And Engineering Sciences, 474 (2018) 20180674-13.
Quantum biology is usually considered to be a new discipline, arising from recent research that suggests that biological phenomena such as photosynthesis, enzyme catalysis, avian navigation or olfaction may not only operate within the bounds of classical physics but also make use of a number of the non-trivial features of quantum mechanics, such as coherence, tunnelling and, perhaps, entanglement. However, although the most significant findings have emerged in the past two decades, the roots of quantum biology go much deeper—to the quantum pioneers of the early twentieth century. We will argue that some of the insights provided by these pioneering physicists remain relevant to our understanding of quantum biology today.
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Mariela D Petkova et al., Optimal Decoding of Cellular Identities in a Genetic Network, Cell, 176 (2019) 844-855.e15.
In developing organisms, spatially prescribed cell identities are thought to be determined by the expression levels of multiple genes. Quantitative tests of this idea, however, require a theoretical framework capable of exposing the rules and precision of cell specification over developmental time. We use the gap gene network in the early fly embryo as an example to show how expression levels of the four gap genes can be jointly decoded into an optimal specification of position with 1% accuracy. The decoder correctly predicts, with no free pa- rameters, the dynamics of pair-rule expression pat- terns at different developmental time points and in various mutant backgrounds. Precise cellular identities are thus available at the earliest stages of development, contrasting the prevailing view of positional information being slowly refined across successive layers of the patterning network. Our results suggest that developmental enhancers closely approximate a mathematically optimal decoding strategy.
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J C Phillips, Self-organized networks: Darwinian evolution of dynein rings, stalks, and stalk heads., Proceedings Of The National Academy Of Sciences Of The United States Of America, 117 (2020) 7799-7802.
Cytoskeletons are self-organized networks based on polymerized proteins: actin, tubulin, and driven by motor proteins, such as myosin, kinesin, and dynein. Their positive Darwinian evolution enables them to approach optimized functionality (self-organized criticality). Dynein has three distinct titled subunits, but how these units connect to function as a molecular motor is mysterious. Dynein binds to tubulin through two coiled coil stalks and a stalk head. The energy used to alter the head binding and propel cargo along tubulin is supplied by ATP at a ring 1,500 amino acids away. Here, we show how many details of this extremely distant interaction are explained by water waves quantified by thermodynamic scaling. Water waves have shaped all proteins throughout positive Darwinian evolution, and many aspects of long-range water-protein interactions are universal (described by self-organized criticality). Dynein water waves resembling tsunami produce nearly optimal energy transport over 1,500 amino acids along dynein's one-dimensional peptide backbone. More specifically, this paper identifies many similarities in the function and evolution of dynein compared to other cytoskeleton proteins such as actin, myosin, and tubulin.
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M B Plenio and S F Huelga, Dephasing-assisted transport: quantum networks and biomolecules, New Journal Of Physics, 10 (2008) 113019-15.
Transport phenomena are fundamental in physics. They allow for information and energy to be exchanged between individual constituents of communication systems, networks or even biological entities. Environmental noise will generally hinder the efficiency of the transport process. However, and contrary to intuition, there are situations in classical systems where thermal fluctuations are actually instrumental in assisting transport phenomena. Here we show that, even at zero temperature, transport of excitations across dissipative quantum networks can be enhanced by local dephasing noise. We explain the underlying physical mechanisms behind this phenomenon and propose possible experimental demonstrations in quantum optics. Our results suggest that the presence of entanglement does not play an essential role for energy transport and may even hinder it. We argue that Nature may be routinely exploiting dephasing noise and show that the transport of excitations in simplified models of light harvesting molecules does benefit from such noise assisted processes. These results point toward the possibility for designing optimized structures for transport, for example in artificial nanostructures, assisted by noise.
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Naren Ramakrishnan and Upinder S Bhalla, Memory Switches in Chemical Reaction Space, Plos Computational Biology, 4 (2008) e1000122-9.
Just as complex electronic circuits are built from simple Boolean gates, diverse biological functions, including signal transduction, differentiation, and stress response, frequently use biochemical switches as a functional module. A relatively small number of such switches have been described in the literature, and these exhibit considerable diversity in chemical topology. We asked if biochemical switches are indeed rare and if there are common chemical motifs and family relationships among such switches. We performed a systematic exploration of chemical reaction space by generating all possible stoichiometrically valid chemical configurations up to 3 molecules and 6 reactions and up to 4 molecules and 3 reactions. We used Monte Carlo sampling of parameter space for each such configuration to generate specific models and checked each model for switching properties. We found nearly 4,500 reaction topologies, or about 10% of our tested configurations, that demonstrate switching behavior. Commonly accepted topological features such as feedback were poor predictors of bistability, and we identified new reaction motifs that were likely to be found in switches. Furthermore, the discovered switches were related in that most of the larger configurations were derived from smaller ones by addition of one or more reactions. To explore even larger configurations, we developed two tools: the ‘‘bistabilizer,’’ which converts almost-bistable systems into bistable ones, and frequent motif mining, which helps rank untested configurations. Both of these tools increased the coverage of our library of bistable systems. Thus, our systematic exploration of chemical reaction space has produced a valuable resource for investigating the key signaling motif of bistability.
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Ken Richardson, It’s the End of the Gene As We Know It, Nautilus, 2019 pp. 1-8.
We’ve all seen the stark headlines: “Being Rich and Successful Is in Your DNA” ( Guardian, July 12); “A New Genetic Test Could Help Determine Children’s Success” (Newsweek, July 10); “Our Fortunetelling Genes” make us (Wall Street Journal, Nov. 16); and so on.
The problem is, many of these headlines are not discussing real genes at all, but a crude statistical model of them, involving dozens of unlikely assumptions. Now, slowly but surely, that whole conceptual model of the gene is being challenged.
We have reached peak gene, and passed it.
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Michael Ruse, Teleology in Biology: Is it a Cause for Concern?, Tree, 4 (1989) 1-4.
Evolutionary biology is distinctively for- ward looking or ‘teleological’ in its wag of thought. In this, it distinguishes itself from the physical sciences. One can ash for the purpose or function of the stegosaur’s fins. One would never ask for the function of a planet. Many, including biologists, worry that such teleology is an unhappy legacy of a Christian past. Although teleology does have its roots in pre-evolutionary thought, there are good reasons why it has persisted, and there are equally good reasons why it should be cherished.
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J A Shapiro, Bacteria are small but not stupid: cognition, natural genetic engineering and socio-bacteriology, Studies In History And Philosophy Of Science Part B, 38 (2007) 807-819.
Forty years’ experience as a bacterial geneticist has taught me that bacteria possess many cognitive, computational and evolutionary capabilities unimaginable in the first six decades of the twentieth century. Analysis of cellular processes such as metabolism, regulation of protein synthesis, and DNA repair established that bacteria continually monitor their external and internal environments and compute functional outputs based on information provided by their sensory apparatus. Studies of genetic recombination, lysogeny, antibiotic resistance and my own work on transposable elements revealed multiple widespread bacterial systems for mobilizing and engineering DNA molecules. Examination of colony development and organization led me to appreciate how extensive multicellular collaboration is among the majority of bacterial species. Contemporary research in many laboratories on cell–cell signaling, symbiosis and pathogen- esis show that bacteria utilise sophisticated mechanisms for intercellular communication and even have the ability to commandeer the basic cell biology of ‘higher’ plants and animals to meet their own needs. This remarkable series of observations requires us to revise basic ideas about biological information processing and recognise that even the smallest cells are sentient beings.
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Sigma-Aldrich, Metabolic Pathways Poster, , 2009 pp. 1-1.
Metabolic Pathways
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Thomas C Südhof and Robert C Malenka, Understanding synapses: past, present, and future., Neuron, 60 (2008) 469-476.
Classical physiological work by Katz, Eccles, and others revealed the central importance of synapses in brain function, and characterized the mechanisms involved in synaptic transmission. Building on this work, major advances in the past two decades have elucidated how synapses work molecularly. In the present perspective, we provide a short description of our personal view of these advances, suggest a series of important future questions about synapses, and discuss ideas about how best to achieve further progress in the field.
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Tuomas E Tahko, Where Do You Get Your Protein? Or: Biochemical Realization, The British Journal For The Philosophy Of Science, 13 (2019) 1-27.
Biochemical kinds such as proteins pose interesting problems for philosophers of science, as they can be studied from the points of view of both biology and chemistry. The relationship between the biological functions of biochemical kinds and the microstructures that they are related to is the key question. This leads us to a more general discussion about ontological reductionism, microstructuralism, and multiple realization at the biology–chemistry interface. On the face of it, biochemical kinds seem to pose a challenge for ontological reductionism and hence motivate a dual theory of chemical and biological kinds, a type of pluralism about natural kinds. But it will be argued that the challenge, which is based on multiple realization, can be addressed. The upshot is that there are reasonable prospects for ontological reductionism about biochemical kinds, which corroborates natural kind monism.
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Jorge Vila, The Marginal Stability of Proteins: How the Jiggling and Wiggling of Atoms is Connected to Neutral Evolution, , 2020 pp. 1-5.
Here we propose that the upper bound marginal stability of proteins is a universal property that includes macro-molecular complexes and is not affected by molecular changes such as mutations and post-translational modifications. We theorize that its existence is a consequence of Afinsen's thermodynamic hypothesis rather than a result of an evolutionary process. This result enables us to conjecture that neutral evolution should also be, with respect to protein stability, a universal phenomenon.
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Peter R Wills and Charles W Carter Jr, Insuperable problems of the genetic code initially emerging in an RNA world, Biosystems, 164 (2018) 155-166.
Differential equations for error-prone information transfer (template replication, transcription or translation) are developed in order to consider, within the theory of autocatalysis, the advent of coded protein synthesis. Variations of these equations furnish a basis for comparing the plausibility of contrasting scenarios for the emergence of specific tRNA aminoacylation, ultimately by enzymes, and the relationship of this process with the origin of the universal system of molecular biological information processing embodied in the Central Dogma. The hypothetical RNA World does not furnish an adequate basis for explaining how this system came into being, but principles of self-organisation that transcend Darwinian natural selection furnish an unexpectedly robust basis for a rapid, concerted transition to genetic coding from a peptide·RNA world.
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Liping Zhu et al., Remarkable problem-solving ability of unicellular amoeboid organism and its mechanism, Royal Society Open Science, 5 (2018) 180396-13.
Choosing a better move correctly and quickly is a fundamental skill of living organisms that corresponds to solving a computationally demanding problem. A unicellular plasmodium of Physarum polycephalum searches for a solution to the travelling salesman problem (TSP) by changing its shape to minimize the risk of being exposed to aversive light stimuli. In our previous studies, we reported the results on the eight-city TSP solution. In this study, we show that the time taken by plasmodium to find a reasonably high-quality TSP solution grows linearly as the problem size increases from four to eight. Interestingly, the quality of the solution does not degrade despite the explosive expansion of the search space. Formulating a computational model, we show that the linear-time solution can be achieved if the intrinsic dynamics could allocate intracellular resources to grow the plasmodium terminals with a constant rate, even while responding to the stimuli. These results may lead to the development of novel analogue computers enabling approximate solutions of complex optimization problems in linear time.
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