Pub Date : 2025-11-12DOI: 10.1016/j.biosystems.2025.105635
Iván Marqués-Campillo , Claudia Arbeitman , Diego Luis González , Oreste Piro
Nullomers — sequences entirely absent from a given genome — exhibit unexpected fractal structures when visualized using Chaos Game Representation (CGR). Unlike nullomers, rare sequences are defined as those that occur infrequently within the genome. Both nullomers and rare sequences conform to Generalised Chargaff’s Second Parity rule at rates that far exceed random expectations. Beginning with nullomer analysis in Homo sapiens, we identified similar fractal patterns among rare sequences with low genomic frequency. We observe a continuous transition in various organisational properties, such as fractal geometry, CpG content, and Hamming distance between consensus sequences as a function of sequence frequency. In addition, our results reveal a fine-grained interpretation of Chargaff’s rule: sequences exhibit frequency-dependent distributional characteristics. Rare sequences, in particular, display distinctive structural order that differentiates them from more abundant sequences, offering new insights into the underlying architecture of the genome as well as its informational structure. Moreover, these architectural and structural distinctions reinforce the perspective that information and meaning are encoded and managed independently within the genomic language.
{"title":"From nullomers to abundant motifs: Fractals, CpG Bias, and Chargaff’s rules in genomic sequences","authors":"Iván Marqués-Campillo , Claudia Arbeitman , Diego Luis González , Oreste Piro","doi":"10.1016/j.biosystems.2025.105635","DOIUrl":"10.1016/j.biosystems.2025.105635","url":null,"abstract":"<div><div>Nullomers — sequences entirely absent from a given genome — exhibit unexpected fractal structures when visualized using Chaos Game Representation (CGR). Unlike nullomers, rare sequences are defined as those that occur infrequently within the genome. Both nullomers and rare sequences conform to Generalised Chargaff’s Second Parity rule at rates that far exceed random expectations. Beginning with nullomer analysis in <em>Homo sapiens</em>, we identified similar fractal patterns among rare sequences with low genomic frequency. We observe a continuous transition in various organisational properties, such as fractal geometry, CpG content, and Hamming distance between consensus sequences as a function of sequence frequency. In addition, our results reveal a fine-grained interpretation of Chargaff’s rule: sequences exhibit frequency-dependent distributional characteristics. Rare sequences, in particular, display distinctive structural order that differentiates them from more abundant sequences, offering new insights into the underlying architecture of the genome as well as its informational structure. Moreover, these architectural and structural distinctions reinforce the perspective that information and meaning are encoded and managed independently within the genomic language.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"259 ","pages":"Article 105635"},"PeriodicalIF":1.9,"publicationDate":"2025-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145521270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-08DOI: 10.1016/j.biosystems.2025.105646
Alexander S. Ermakov
Nikolai Konstantinovich Koltsov (1872–1940) lived and worked in an epoch when biology was rapidly transitioning from a descriptive to an experimental science. Koltsov foresaw and, to some extent, predetermined the development of the most important areas of modern biology: evolutionary genetics and synthetic theory of evolution, mutagenesis, human genetics, cellular and molecular biology, developmental genetics, developmental biology, and epigenetics. He had visionary ideas about "template synthesis", which underlies the process of copying genes and the possible involvement of methylation in the modification of molecules of biological inheritance. For political reasons, the development of his scientific school in the USSR was terminated, and his name was forgotten for several decades. The scientific legacy of Nikolai Koltsov remains relevant in our days.
{"title":"Nikolai Koltsov and his work, which anticipated many ideas in modern cellular and molecular biology, genetics, and epigenetics. Toward the 100th anniversary of the concept of template biosynthesis","authors":"Alexander S. Ermakov","doi":"10.1016/j.biosystems.2025.105646","DOIUrl":"10.1016/j.biosystems.2025.105646","url":null,"abstract":"<div><div>Nikolai Konstantinovich Koltsov (1872–1940) lived and worked in an epoch when biology was rapidly transitioning from a descriptive to an experimental science. Koltsov foresaw and, to some extent, predetermined the development of the most important areas of modern biology: evolutionary genetics and synthetic theory of evolution, mutagenesis, human genetics, cellular and molecular biology, developmental genetics, developmental biology, and epigenetics. He had visionary ideas about \"template synthesis\", which underlies the process of copying genes and the possible involvement of methylation in the modification of molecules of biological inheritance. For political reasons, the development of his scientific school in the USSR was terminated, and his name was forgotten for several decades. The scientific legacy of Nikolai Koltsov remains relevant in our days.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"259 ","pages":"Article 105646"},"PeriodicalIF":1.9,"publicationDate":"2025-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145490902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1016/j.biosystems.2025.105641
Laureano Castro , Daniel Castro-Cañadilla , Miguel Ángel Castro-Nogueira , Miguel Ángel Toro
One way to investigate the origins of cumulative culture is by examining the increasing complexity of lithic technologies in the hominin lineage. This study presents a simplified model of cultural transmission in Homo erectus and Homo heidelbergensis, focusing on the emergence of cumulative culture in relation to Oldowan, Acheulean, and the transition to Mode 3 technologies. Acheulean toolmaking likely required high-fidelity transmission, possibly supported by early forms of teaching. However, the remarkable technological conservatism of the Acheulean record contrasts with the rapid accumulation of innovations in modern humans. Our model aims to shed light on this circumstance by analysing the roles played by imitation and early forms of teaching. Each lithic technology is classified into three behavioural levels (0–2), representing increasing complexity and adaptive value, which can be acquired through individual learning or social transmission. We introduce two genotypes: the Imitator, which enables basic social learning, and the Assessor, which adds evaluative teaching between parents and offspring. We analyse the cultural dynamics generated by each genotype in pure populations. Our results suggest that incremental cumulative culture depends critically on offspring reliably replicating the most complex behaviours of their parents. This dynamic favours the evolution of the Assessor genotype, as it enhances parent-offspring behavioural resemblance. Nonetheless, when replication fidelity falls short of establishing the highest level of complexity behaviours (Level 2) predominant, the Assessor genotype may inadvertently reinforce cultural stasis instead of driving cumulative cultural evolution, ultimately hindering the transition from Level 1 to Level 2 behaviours via individual learning.
{"title":"Cultural accumulation or stasis? The impact of imitation and early teaching on hominin cultural evolution","authors":"Laureano Castro , Daniel Castro-Cañadilla , Miguel Ángel Castro-Nogueira , Miguel Ángel Toro","doi":"10.1016/j.biosystems.2025.105641","DOIUrl":"10.1016/j.biosystems.2025.105641","url":null,"abstract":"<div><div>One way to investigate the origins of cumulative culture is by examining the increasing complexity of lithic technologies in the hominin lineage. This study presents a simplified model of cultural transmission in <em>Homo erectus</em> and <em>Homo heidelbergensis</em>, focusing on the emergence of cumulative culture in relation to Oldowan, Acheulean, and the transition to Mode 3 technologies. Acheulean toolmaking likely required high-fidelity transmission, possibly supported by early forms of teaching. However, the remarkable technological conservatism of the Acheulean record contrasts with the rapid accumulation of innovations in modern humans. Our model aims to shed light on this circumstance by analysing the roles played by imitation and early forms of teaching. Each lithic technology is classified into three behavioural levels (0–2), representing increasing complexity and adaptive value, which can be acquired through individual learning or social transmission. We introduce two genotypes: the <em>Imitator</em>, which enables basic social learning, and the <em>Assessor</em>, which adds evaluative teaching between parents and offspring. We analyse the cultural dynamics generated by each genotype in pure populations. Our results suggest that incremental cumulative culture depends critically on offspring reliably replicating the most complex behaviours of their parents. This dynamic favours the evolution of the Assessor genotype, as it enhances parent-offspring behavioural resemblance. Nonetheless, when replication fidelity falls short of establishing the highest level of complexity behaviours (Level 2) predominant, the Assessor genotype may inadvertently reinforce cultural stasis instead of driving cumulative cultural evolution, ultimately hindering the transition from Level 1 to Level 2 behaviours via individual learning.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"258 ","pages":"Article 105641"},"PeriodicalIF":1.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-07DOI: 10.1016/j.biosystems.2025.105645
Breno B. Just , Sávio Torres de Farias
No consensus exists on how to define cognition. One source of contention is the attribution of cognition to aneural organisms. The claim that aneural organisms are cognitive stems from existing definitions in the cognitive literature and from the recognition that these organisms possess similar processes to those found in cognitive animals. The most conspicuous feature of cognition is that it is a collection of processes: perception, memory, decision-making, problem-solving, and so on. It has been shown that aneural groups, from bacteria to single-celled eukaryotes to plants and fungi, possess a rich machinery to implement these processes. Despite that, many researchers still dispute the idea of aneural cognition. They claim that their processes are too limited, that finding a bunch of processes in aneural organism does not suffice to make them cognitive, or that cognition needs specific requirements, which often involve high-level processes. We challenge these criticisms through an analysis of E. coli. We gather evidence for the existence of a rich cognitive repertoire in this organism, showcasing how a simple bacterium is capable of realizing multiple components of cognition. E. coli has an extensive molecular machinery that implements the various components deemed necessary for cognition. By analyzing E. coli, we can also capture an essential aspect of cognition's nature: cognition is a global process that emerges through the interdependent orchestration of its components, which enables an organism to grasp aspects of its world. As such, it represents a fundamental biological process for every cellular-based organism.
{"title":"A case for aneural cognition: E. coli and its cognitive repertoire","authors":"Breno B. Just , Sávio Torres de Farias","doi":"10.1016/j.biosystems.2025.105645","DOIUrl":"10.1016/j.biosystems.2025.105645","url":null,"abstract":"<div><div>No consensus exists on how to define cognition. One source of contention is the attribution of cognition to aneural organisms. The claim that aneural organisms are cognitive stems from existing definitions in the cognitive literature and from the recognition that these organisms possess similar processes to those found in cognitive animals. The most conspicuous feature of cognition is that it is a collection of processes: perception, memory, decision-making, problem-solving, and so on. It has been shown that aneural groups, from bacteria to single-celled eukaryotes to plants and fungi, possess a rich machinery to implement these processes. Despite that, many researchers still dispute the idea of aneural cognition. They claim that their processes are too limited, that finding a bunch of processes in aneural organism does not suffice to make them cognitive, or that cognition needs specific requirements, which often involve high-level processes. We challenge these criticisms through an analysis of <em>E. coli</em>. We gather evidence for the existence of a rich cognitive repertoire in this organism, showcasing how a simple bacterium is capable of realizing multiple components of cognition. <em>E. coli</em> has an extensive molecular machinery that implements the various components deemed necessary for cognition. By analyzing <em>E. coli,</em> we can also capture an essential aspect of cognition's nature: cognition is a global process that emerges through the interdependent orchestration of its components, which enables an organism to grasp aspects of its world. As such, it represents a fundamental biological process for every cellular-based organism.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"258 ","pages":"Article 105645"},"PeriodicalIF":1.9,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145483784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-05DOI: 10.1016/j.biosystems.2025.105644
Kentaro Inoue
Understanding complex molecular interactions in biological systems requires both precise simulation and effective visualization of dynamic processes. Traditional tools have often presented static network diagrams and segregated simulation results, making it challenging to concurrently interpret network structure and temporal dynamics. In this study, we introduce SBDyNetVis, a novel Python-based library that transforms network and time-course data into interactive JavaScript visualizations using Cytoscape.js. SBDyNetVis integrates multiple network layout algorithms with animated representations of nodes and edges, allowing users to intuitively explore reaction kinetics, flux equations, and dynamic changes all on a single platform. We demonstrate the utility of SBDyNetVis by successfully converting 913 models from BioModels and by applying the tool in a detailed case study of the IKK-NFκB-IκB reaction. Its web-based interface promotes seamless data sharing and collaboration among researchers with varying levels of technical expertise. By bridging the gap between static network representation and dynamic simulation visualization, SBDyNetVis paves the way for deeper insights into cellular processes and holds significant potential for advancing systems biology research. SBDyNetVis is available at https://github.com/kntrinoue/SBDyNetVis.
理解生物系统中复杂的分子相互作用需要精确的模拟和动态过程的有效可视化。传统工具通常呈现静态网络图和分离的仿真结果，这使得同时解释网络结构和时间动态具有挑战性。在本研究中，我们介绍了SBDyNetVis，一个新颖的基于python的库，它使用Cytoscape.js将网络和时间过程数据转换为交互式JavaScript可视化。SBDyNetVis集成了多种网络布局算法，具有节点和边缘的动画表示，允许用户直观地探索反应动力学，通量方程和动态变化，所有这些都在单个平台上。我们成功地转换了913个生物模型，并将该工具应用于ikk - nf - κ b - i - κ b反应的详细案例研究，从而证明了SBDyNetVis的实用性。其基于网络的界面促进了具有不同技术专长水平的研究人员之间的无缝数据共享和协作。通过弥合静态网络表示和动态仿真可视化之间的差距，SBDyNetVis为深入了解细胞过程铺平了道路，并具有推进系统生物学研究的巨大潜力。SBDyNetVis可在https://github.com/kntrinoue/SBDyNetVis获得。
{"title":"SBDyNetVis: a visualization tool of dynamic network for systems biology model","authors":"Kentaro Inoue","doi":"10.1016/j.biosystems.2025.105644","DOIUrl":"10.1016/j.biosystems.2025.105644","url":null,"abstract":"<div><div>Understanding complex molecular interactions in biological systems requires both precise simulation and effective visualization of dynamic processes. Traditional tools have often presented static network diagrams and segregated simulation results, making it challenging to concurrently interpret network structure and temporal dynamics. In this study, we introduce SBDyNetVis, a novel Python-based library that transforms network and time-course data into interactive JavaScript visualizations using Cytoscape.js. SBDyNetVis integrates multiple network layout algorithms with animated representations of nodes and edges, allowing users to intuitively explore reaction kinetics, flux equations, and dynamic changes all on a single platform. We demonstrate the utility of SBDyNetVis by successfully converting 913 models from BioModels and by applying the tool in a detailed case study of the IKK-NFκB-IκB reaction. Its web-based interface promotes seamless data sharing and collaboration among researchers with varying levels of technical expertise. By bridging the gap between static network representation and dynamic simulation visualization, SBDyNetVis paves the way for deeper insights into cellular processes and holds significant potential for advancing systems biology research. SBDyNetVis is available at <span><span>https://github.com/kntrinoue/SBDyNetVis</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"258 ","pages":"Article 105644"},"PeriodicalIF":1.9,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.biosystems.2025.105642
Joseph J. Trukovich
Consciousness requires explanation for how biological architectures reliably generate it. This paper introduces Value Saturation, advancing an identity claim: phenomenal consciousness IS explicit recursive self-modeling saturated by homeostatic significance under perspectival entrapment. Building on the Reaction to Reflection framework, the theory distinguishes sentience (implicit recursion under survival stakes, Level 2) from subjective consciousness (explicit recursion where self-models become manipulable, Levels 4–5). Three integrated components prove necessary: interoceptive binding, homeostatic saturation, and perspectival entrapment. Testable predictions include developmental progression from birth sentience to subjective consciousness around ages 3–5, awareness-manipulation asymmetry, and clinical dissociations producing aberrant rather than absent phenomenology. Converging evidence from prediction error processing, homeostatic feelings, metacognitive hierarchies, and biological computing's thermodynamic advantages supports these requirements. The framework specifies falsification criteria and transforms consciousness into an empirically tractable investigation of organizational transitions in biological systems under thermodynamic constraints.
{"title":"Value saturation: Architecture of subjective necessity","authors":"Joseph J. Trukovich","doi":"10.1016/j.biosystems.2025.105642","DOIUrl":"10.1016/j.biosystems.2025.105642","url":null,"abstract":"<div><div>Consciousness requires explanation for how biological architectures reliably generate it. This paper introduces Value Saturation, advancing an identity claim: phenomenal consciousness IS explicit recursive self-modeling saturated by homeostatic significance under perspectival entrapment. Building on the Reaction to Reflection framework, the theory distinguishes sentience (implicit recursion under survival stakes, Level 2) from subjective consciousness (explicit recursion where self-models become manipulable, Levels 4–5). Three integrated components prove necessary: interoceptive binding, homeostatic saturation, and perspectival entrapment. Testable predictions include developmental progression from birth sentience to subjective consciousness around ages 3–5, awareness-manipulation asymmetry, and clinical dissociations producing aberrant rather than absent phenomenology. Converging evidence from prediction error processing, homeostatic feelings, metacognitive hierarchies, and biological computing's thermodynamic advantages supports these requirements. The framework specifies falsification criteria and transforms consciousness into an empirically tractable investigation of organizational transitions in biological systems under thermodynamic constraints.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"258 ","pages":"Article 105642"},"PeriodicalIF":1.9,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-04DOI: 10.1016/j.biosystems.2025.105640
Gordana Dodig-Crnkovic
Many physical systems retain traces of their past, but living systems differ in that they use memory for anticipation. This paper develops the thesis that anticipation depends on memory. In living systems, stored information about past states enables the prediction and modulation of future behavior. Drawing on Robert Rosen's theory of anticipatory systems, Friston's free-energy principle, and recent examples from microbiology, immunology, and cognition, I argue that Rosen's “model” is the organized memory of a system. Memory—whether mechanical, chemical, genetic, epigenetic, bioelectric, neural, or cultural—provides the substrate for anticipation, projecting possible futures and constraining present behavior. Examples across biological scales illustrate how this works in practice. Bacteria record viral encounters and use these genomic memories to defend against reinfection. In E. coli, biochemical traces of past interactions direct chemotaxis. Yeast cells store epigenetic stress memories that accelerate adaptation. With the advent of nervous systems, anticipation becomes centralized in internal neural models, enabling flexible simulations of organism–environment interactions. In all cases, anticipatory memory underlies teleonomy as goal-directedness that emerges from evolutionary and developmental processes. Top-down causation plays a central role in shaping the constraints that give rise to purposive, self-maintaining behavior. System-level goals emerge from past-informed constraints, giving living systems their distinctive autonomy, adaptivity, and creativity.
{"title":"Anticipation, memory, and top-down causation in living systems","authors":"Gordana Dodig-Crnkovic","doi":"10.1016/j.biosystems.2025.105640","DOIUrl":"10.1016/j.biosystems.2025.105640","url":null,"abstract":"<div><div>Many physical systems retain traces of their past, but living systems differ in that they use memory for anticipation. This paper develops the thesis that anticipation depends on memory. In living systems, stored information about past states enables the prediction and modulation of future behavior. Drawing on Robert Rosen's theory of anticipatory systems, Friston's free-energy principle, and recent examples from microbiology, immunology, and cognition, I argue that Rosen's “model” is the organized memory of a system. Memory—whether mechanical, chemical, genetic, epigenetic, bioelectric, neural, or cultural—provides the substrate for anticipation, projecting possible futures and constraining present behavior. Examples across biological scales illustrate how this works in practice. Bacteria record viral encounters and use these genomic memories to defend against reinfection. In E. coli, biochemical traces of past interactions direct chemotaxis. Yeast cells store epigenetic stress memories that accelerate adaptation. With the advent of nervous systems, anticipation becomes centralized in internal neural models, enabling flexible simulations of organism–environment interactions. In all cases, anticipatory memory underlies teleonomy as goal-directedness that emerges from evolutionary and developmental processes. Top-down causation plays a central role in shaping the constraints that give rise to purposive, self-maintaining behavior. System-level goals emerge from past-informed constraints, giving living systems their distinctive autonomy, adaptivity, and creativity.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"259 ","pages":"Article 105640"},"PeriodicalIF":1.9,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145453925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-11-03DOI: 10.1016/j.biosystems.2025.105632
Ian Todd
We show that the thermodynamic advantage of biological, continuous substrates over digital simulators arises from timing inaccessibility: below the Landauer threshold, temporal order cannot be irreversibly registered without dissipating per binary decision. Consequently, exponentially many micro-trajectories map to the same observable outcome (path degeneracy). Continuous high-dimensional substrates exploit this by integrating sub-Landauer couplings during evolution and paying only at projection (dimensional collapse to a low-dimensional output).
We derive a Projection Bound for quasistatic projection at effective temperature : (0.1)which reduces under typical-set conditions to . Combined with a Temporal Registration Bound (order over bins needs bits), we quantify the gap: enumerative digital tracking scales exponentially with dimension, whereas projection cost scales like .
For biologically plausible parameters, we estimate degeneracies of
{"title":"Timing inaccessibility and the projection bound: Resolving Maxwell’s demon for continuous biological substrates","authors":"Ian Todd","doi":"10.1016/j.biosystems.2025.105632","DOIUrl":"10.1016/j.biosystems.2025.105632","url":null,"abstract":"<div><div>We show that the thermodynamic advantage of biological, continuous substrates over digital simulators arises from <em>timing inaccessibility</em>: below the Landauer threshold, temporal order cannot be irreversibly registered without dissipating <span><math><mrow><mo>≥</mo><msub><mrow><mi>k</mi></mrow><mrow><mi>B</mi></mrow></msub><mi>T</mi><mo>ln</mo><mn>2</mn></mrow></math></span> per binary decision. Consequently, exponentially many micro-trajectories map to the same observable outcome (<em>path degeneracy</em>). Continuous high-dimensional substrates exploit this by integrating sub-Landauer couplings during evolution and paying only at <em>projection</em> (dimensional collapse to a low-dimensional output).</div><div>We derive a <strong>Projection Bound</strong> for quasistatic projection at effective temperature <span><math><msub><mrow><mi>T</mi></mrow><mrow><mi>eff</mi></mrow></msub></math></span>: <span><span><span>(0.1)</span><span><math><mrow><msub><mrow><mi>E</mi></mrow><mrow><mi>collapse</mi></mrow></msub><mo>≥</mo><msub><mrow><mi>k</mi></mrow><mrow><mi>B</mi></mrow></msub><msub><mrow><mi>T</mi></mrow><mrow><mi>eff</mi></mrow></msub><mfenced><mrow><mo>ln</mo><mfrac><mrow><msub><mrow><mi>N</mi></mrow><mrow><mi>ɛ</mi><mo>,</mo><mi>pre</mi></mrow></msub></mrow><mrow><msub><mrow><mi>N</mi></mrow><mrow><mi>ɛ</mi><mo>,</mo><mi>post</mi></mrow></msub></mrow></mfrac><mo>−</mo><mi>KL</mi><mspace></mspace><mfenced><mrow><msup><mrow><mi>p</mi></mrow><mrow><mi>pre</mi></mrow></msup><mspace></mspace><mo>∥</mo><mspace></mspace><msub><mrow><mi>U</mi></mrow><mrow><mi>pre</mi></mrow></msub></mrow></mfenced><mo>+</mo><mi>KL</mi><mspace></mspace><mfenced><mrow><msup><mrow><mi>p</mi></mrow><mrow><mi>post</mi></mrow></msup><mspace></mspace><mo>∥</mo><mspace></mspace><msub><mrow><mi>U</mi></mrow><mrow><mi>post</mi></mrow></msub></mrow></mfenced></mrow></mfenced></mrow></math></span></span></span>which reduces under typical-set conditions to <span><math><mrow><msub><mrow><mi>E</mi></mrow><mrow><mi>collapse</mi></mrow></msub><mo>≥</mo><msub><mrow><mi>k</mi></mrow><mrow><mi>B</mi></mrow></msub><msub><mrow><mi>T</mi></mrow><mrow><mi>eff</mi></mrow></msub><mo>ln</mo><mrow><mo>(</mo><msub><mrow><mi>N</mi></mrow><mrow><mi>ɛ</mi><mo>,</mo><mi>pre</mi></mrow></msub><mo>/</mo><msub><mrow><mi>N</mi></mrow><mrow><mi>ɛ</mi><mo>,</mo><mi>post</mi></mrow></msub><mo>)</mo></mrow></mrow></math></span>. Combined with a <strong>Temporal Registration Bound</strong> (order over <span><math><mi>M</mi></math></span> bins needs <span><math><mrow><msub><mrow><mo>log</mo></mrow><mrow><mn>2</mn></mrow></msub><mi>M</mi><mo>!</mo></mrow></math></span> bits), we quantify the gap: enumerative digital tracking scales exponentially with dimension, whereas projection cost scales like <span><math><mrow><mo>ln</mo><mi>G</mi><mo>∼</mo><mi>D</mi></mrow></math></span>.</div><div>For biologically plausible parameters, we estimate degeneracies of <span><math><mrow><mn>1</mn><msup><mrow><m","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"258 ","pages":"Article 105632"},"PeriodicalIF":1.9,"publicationDate":"2025-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.biosystems.2025.105636
Massimo Di Giulio
The progenote- > cell transition defines the evolutionary stage of the formation of a domain of life. Indeed, the progenote evolutionary stage cannot be or have a domain of life, because the progenote stage does not, by definition, contain cells, being an evolutionary stage with a genotype-phenotype relationship still in formation. Therefore, the progenote stage is certainly cell-free and therefore cannot be a domain of life, which is instead made up of cells. Consequently, it is at the moment in which a cell emerged from the progenote stage that the first domain of life was defined. In fact, this would be the first appearance of a cell in the history of life, since the progenote stage is cell-free. All of this would define the birth of a domain of life because it would represent the first and precise evolutionary point at which the first cell would be born, after the progenote stage. Furthermore, the progenote- > cell transition is completely reflected in the transition from evolving genetic code to frozen genetic code. That is to say, a genetic code in evolution, i.e. still originating, would precisely reflect the definition of progenote because a code that is still originating should have a genotype-phenotype relationship yet to be defined and would identify, by definition, the stage of the progenote. A frozen genetic code, a fully formed, modern genetic code, would imply the cell stage, that is, the abandonment of the progenote stage. Indeed, nothing more than a modern genetic code might indicate the achievement of the cell stage because a fully developed genetic code would imply modern proteins, which in turn would imply that all the structures of that particular evolutionary stage would certainly belong to a cell stage, precisely because they are structures to be considered, in some sense, complete and definitive. In conclusion, the simple observation of specific variants of the genetic code would provide the opportunity to easily identify the domains of life because a genetic code possessed only by a certain type of organism would witness the transition from evolving genetic code to frozen genetic code and consequently the transition from progenote to cell, and would therefore identify a domain of life. In this way, that is to say, by using some variants of the genetic code, the following domains of life have been identified: Bacteria, Methanogens, and Non-Methanogenic Archaea. Eukaryotes, having the same genetic code as non-methanogenic archaea, would belong to the same domain as the latter. The discussion focuses on these three domains of life and their relationship with the domains of life suggested by other hypotheses, and on properties of the variants of the genetic code used to identify these domains.
{"title":"How many and which types of primary cells (domains of life) emerged from LUCA, identified employing different genetic codes","authors":"Massimo Di Giulio","doi":"10.1016/j.biosystems.2025.105636","DOIUrl":"10.1016/j.biosystems.2025.105636","url":null,"abstract":"<div><div>The progenote- > cell transition defines the evolutionary stage of the formation of a domain of life. Indeed, the progenote evolutionary stage cannot be or have a domain of life, because the progenote stage does not, by definition, contain cells, being an evolutionary stage with a genotype-phenotype relationship still in formation. Therefore, the progenote stage is certainly cell-free and therefore cannot be a domain of life, which is instead made up of cells. Consequently, it is at the moment in which a cell emerged from the progenote stage that the first domain of life was defined. In fact, this would be the first appearance of a cell in the history of life, since the progenote stage is cell-free. All of this would define the birth of a domain of life because it would represent the first and precise evolutionary point at which the first cell would be born, after the progenote stage. Furthermore, the progenote- > cell transition is completely reflected in the transition from evolving genetic code to frozen genetic code. That is to say, a genetic code in evolution, i.e. still originating, would precisely reflect the definition of progenote because a code that is still originating should have a genotype-phenotype relationship yet to be defined and would identify, by definition, the stage of the progenote. A frozen genetic code, a fully formed, modern genetic code, would imply the cell stage, that is, the abandonment of the progenote stage. Indeed, nothing more than a modern genetic code might indicate the achievement of the cell stage because a fully developed genetic code would imply modern proteins, which in turn would imply that all the structures of that particular evolutionary stage would certainly belong to a cell stage, precisely because they are structures to be considered, in some sense, complete and definitive. In conclusion, the simple observation of specific variants of the genetic code would provide the opportunity to easily identify the domains of life because a genetic code possessed only by a certain type of organism would witness the transition from evolving genetic code to frozen genetic code and consequently the transition from progenote to cell, and would therefore identify a domain of life. In this way, that is to say, by using some variants of the genetic code, the following domains of life have been identified: Bacteria, Methanogens, and Non-Methanogenic Archaea. Eukaryotes, having the same genetic code as non-methanogenic archaea, would belong to the same domain as the latter. The discussion focuses on these three domains of life and their relationship with the domains of life suggested by other hypotheses, and on properties of the variants of the genetic code used to identify these domains.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"258 ","pages":"Article 105636"},"PeriodicalIF":1.9,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145418440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-10-30DOI: 10.1016/j.biosystems.2025.105638
Matthew Wright, Kevin M. Downard
Prime mass amino acids residues, assigned based upon the nominal mass of their repeating structure in peptides and proteins, provide a more rigid physicochemical definition not achieved with other more common classifiers. Found to occur more often than by chance, the nine prime residues are predominantly hydrophobic in character that play an important role in protein stability and folding. A global study of the prevalence of particular single point mutations across several hundred proteins has revealed that mutations which retain a prime mass residue are favoured over those that lose them. Further, the mutation of a non-prime to prime residue is favoured over the retention of a non-prime residue. The introduction of the prime alanine residue, in particular, is found to occur in over 50 % of cases when a prime or non-prime residue mutates, based on data extracted across almost 16,000 mutations for within a wide range of proteins. Mutation to the prime residues isoleucine (I) and leucine (L), threonine (T) and proline (P) are also found to predominate. This is evident across the many hundreds of database entries and within a single transmembrane protein previously identified to be among the richest-prime residue protein known. Consideration is given to the impact of these observations on protein stability and the advantages they confer to protein evolution. It is shown that the majority of prime residues are recruited early in the development of the genetic code. Last common universal ancestral (LUCA) proteins are enriched in smaller molecular weight, hydrophobic prime amino acids rather than larger aliphatic non-prime ones.
{"title":"Prevalence of prime mass residues in single point mutations and their importance to protein stability, function and evolution","authors":"Matthew Wright, Kevin M. Downard","doi":"10.1016/j.biosystems.2025.105638","DOIUrl":"10.1016/j.biosystems.2025.105638","url":null,"abstract":"<div><div>Prime mass amino acids residues, assigned based upon the nominal mass of their repeating structure in peptides and proteins, provide a more rigid physicochemical definition not achieved with other more common classifiers. Found to occur more often than by chance, the nine prime residues are predominantly hydrophobic in character that play an important role in protein stability and folding. A global study of the prevalence of particular single point mutations across several hundred proteins has revealed that mutations which retain a prime mass residue are favoured over those that lose them. Further, the mutation of a non-prime to prime residue is favoured over the retention of a non-prime residue. The introduction of the prime alanine residue, in particular, is found to occur in over 50 % of cases when a prime or non-prime residue mutates, based on data extracted across almost 16,000 mutations for within a wide range of proteins. Mutation to the prime residues isoleucine (I) and leucine (L), threonine (T) and proline (P) are also found to predominate. This is evident across the many hundreds of database entries and within a single transmembrane protein previously identified to be among the richest-prime residue protein known. Consideration is given to the impact of these observations on protein stability and the advantages they confer to protein evolution. It is shown that the majority of prime residues are recruited early in the development of the genetic code. Last common universal ancestral (LUCA) proteins are enriched in smaller molecular weight, hydrophobic prime amino acids rather than larger aliphatic non-prime ones.</div></div>","PeriodicalId":50730,"journal":{"name":"Biosystems","volume":"258 ","pages":"Article 105638"},"PeriodicalIF":1.9,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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