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A Sourcebook for the Worldwide Discovery of a Creative Organic Universe
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Genesis Vision
Learning Planet
Organic Universe
Earth Life Emerge
Genesis Future
Recent Additions

V. Life's Evolutionary Development Organizes Itself: A 2020s Genesis Synthesis

B. Systems Biology Integrates: Genomes, Networks, Symbiosis, Deep Homology

Ashe, Alyson, et al, eds. How does Epigenetics Influence the Course of Evolution? Philosophical Transaction of the Royal Society B. April, 2021. The editors are AA and Benjamin Oldroyd, University of Sydney, and Vincent Colot, CNRS, Paris and here introduce this special issue which surveys an expanding array of influences upon “genomic” phenomena beyond nucleotides alone. See, for example< The Impact of Epigenetic Information on Genome Evolution by V. Soojin, et al and Epigenetic Inheritance and Evolution by Laurent Loison.

Epigenetics is the study of changes in gene activity that are transmitted through cell divisions but cannot be explained by changes in DNA sequence. Epigenetic mechanisms are central to development of genome integrity and for the ability of animals and plants to adjust to environments without the need for genetic change. However, because epigenetic states are somewhat reset at every generation, their effect has previously been seen as a minor contribution to evolutionary change. The papers in this theme issue describe how epigenetic variations make direct and indirect contributions to evolutionary processes including adaptation to new environments, climate change, species invasiveness, sex chromosome differentiation, and onto speciation. (Issue summary)

Balleza, Enrique, et al. Critical Dynamics in Genetic Regulatory Networks. PLoS One. 3/6, 2008. A team from the Universidad Nacional Autónoma de México, University of Calgary, and Institute for Systems Biology, Seattle, including Stuart Kauffman, find the natural universality of critically poised self-organized nonlinear phenomena to be equally and effectively present in genomes. As the extended Abstract conveys, these heretofore unnoticed qualities impart an inherent stability along with environmental and evolutionary responsiveness. By these insights across genetic research, a new relational dimension is being added beyond nucleotide molecules alone.

The coordinated expression of the different genes in an organism is essential to sustain functionality under the random external perturbations to which the organism might be subjected. To cope with such external variability, the global dynamics of the genetic network must possess two central properties. (a) It must be robust enough as to guarantee stability under a broad range of external conditions, and (b) it must be flexible enough to recognize and integrate specific external signals that may help the organism to change and adapt to different environments. This compromise between robustness and adaptability has been observed in dynamical systems operating at the brink of a phase transition between order and chaos. Such systems are termed critical. Thus, criticality, a precise, measurable, and well characterized property of dynamical systems, makes it possible for robustness and adaptability to coexist in living organisms.

In this work we investigate the dynamical properties of the gene transcription networks reported for S. cerevisiae, E. coli, and B. subtilis, as well as the network of segment polarity genes of D. melanogaster, and the network of flower development of A. thaliana. We use hundreds of microarray experiments to infer the nature of the regulatory interactions among genes, and implement these data into the Boolean models of the genetic networks. Our results show that, to the best of the current experimental data available, the five networks under study indeed operate close to criticality. The generality of this result suggests that criticality at the genetic level might constitute a fundamental evolutionary mechanism that generates the great diversity of dynamically robust living forms that we observe around us. (Abstract)

Bancaud, Aurelien, et al. Molecular Crowing Affects Diffusion and Binding of Nuclear Proteins in Heterochromatin and Reveals the Fractal Organization of Chromatin. EMBO Journal. 28/3785, 2009. “Chromatin” is a composite of DNA, RNA and proteins that makes up the nucleus of a cell. A research team at the European Molecular Biology Laboratory EMBL, Heidelberg, led by Jan Ellenberg, finds its architectural dynamics to exhibit an optimum packing density due to self-similarities across several scales and versions. Cellular nuclei self-organize their components and phases into this most efficient mode. These insights have achieved peer notice such as “Fractal Geometry in the Nucleus” by Jamey McNally and Davide Mazza (EMBO Journal 29/2, 2010), Claire Ainsworth’s “Cells Go Fractal: Mathematical Patterns Rule the Behavior of Molecules in the Nucleus” (Nature News September 4, 2009), and especially Erez Lieberman-Aiden, et al “Comprehensive Mapping of Long-range Interactions Reveals Folding Principles of the Human Genome” (Science 326/289, 2009).

The kinetic signatures of these crowding consequences allow us to derive a fractal model of chromatin organization, which explains why the dynamics of soluble nuclear proteins are affected independently of their size. This model further shows that the fractal architecture differs between heterochromatin and euchromatin, and predicts that chromatin proteins use different target-search strategies in the two compartments. We propose that fractal crowding is a fundamental principle of nuclear organization, particularly of heterochromatin maintenance. (Abstract, 3785)

Bapteste, Eric, et al. Networks: Expanding Evolutionary Thinking. Trends in Genetics. 29/8, 2013. A report on a Future of Phylogenetic Networks meeting in October 2012 in London about pervasive applications of this natural geometry to life’s variegated development course. In essence, trees become nuanced into more branchy, webby networks. See for example In the Light of Deep Coalescence: Revisiting Trees Within Networks by Jiafan Zhu, et al at arXiv:1606.07350 as an organic interconnectivity becomes increasingly evident. The term reticulate which means “resembling a network” is often used to describe.

Bizzarri, Mariano, et al. Theoretical Aspects of Systems Biology. Progress in Biophysics and Molecular Biology. 112/1-2, 2013. Keywords are Systems Biology, Biophysical Constraints, Complexity, Fractals, Non-Linearity, Morphogenetic Fields. A decade on, Sapienza University of Rome research physicians provide a cogent survey of this holistic reassembly to better understand life’s genomic and metabolic essences. Actually, after many decades of identifying all the molecular, cellular, and organismic pieces, a new obvious phase is entered to put them back together via their interconnective networks and constant modularity, namely “putting genes in context.” The august discovery to then be made is that a similarly invariant topology and vitality can be observed at each and every nested scale and instance. A breakthrough payoff is to treat cancers as dynamic complexities, for example in Seminars in Cancer Biology, 21/3, 2011. See also by Bizzarri, et al (Quote 2) “Physical Forces and Non-linear Dynamics Mould Fractal Cell Shape” in Histology and Histopathology 28/2, 2013, and “Systems Biology for Molecular Life Sciences and its Impact in Biomedicine” by Miguel Medina herein.

The natural world consists of hierarchical levels of complexity that range from subatomic particles and molecules to ecosystems and beyond. This implies that, in order to explain the features and behavior of a whole system, a theory might be required that would operate at the corresponding hierarchical level, i.e. where self-organization processes take place. In the past, biological research has focused on questions that could be answered by a reductionist program of genetics. The organism (and its development) was considered an epiphenomenona of its genes. However, a profound rethinking of the biological paradigm is now underway and it is likely that such a process will lead to a conceptual revolution emerging from the ashes of reductionism. This revolution implies the search for general principles on which a cogent theory of biology might rely. Because much of the logic of living systems is located at higher levels, it is imperative to focus on them. Indeed, both evolution and physiology work on these levels. Thus, by no means Systems Biology could be considered a ‘simple’ ‘gradual’ extension of Molecular Biology. (Abstract, Bizzarri 1)

Cell shape is mainly determined by biophysical constraints, interacting according to non-linear dynamics upon the basic units provided by the genome. In turn, the specific configuration a cell acquires plays a fundamental, permissive role in modulating gene expression and many other complex biological functions. Cell shape is tightly connected to cell activity and can be considered the most critical determinant of cell function. As a consequence, measurable parameters describing shape could be considered as ‘omics’ descriptors of the specific level of observation represented by the cell-stroma system. Such an approach promises to formalize some of the underlying basic mechanisms and, ultimately, provide a holistic understanding of the biological processes. (Abstract, Bizzarri 2)

Bogdan, Paul, et al. Biological Networks Across Scales. Integrative & Comparative Biology. 61/6, 2022. Eleven coauthors across the USA including Gustavo Caetano-Anolles and Hyunji Kim post a lead paper in this special NSF Rules of Life edition. A long subtitle is The Theoretical and Empirical Foundations for Time-Varying Networks that Connect Structure and Function across Levels of Biological Organization. As a capsule, a central theme these studies is to include the primary anatomical and physiological presence of dynamic multiplex webworks, as if a missing element until now, as they serve to give form and function to the evolving and metabolic cellular components. We note again that by so doing the occasion of a universal repetition in kind of an iconic node and link commonality becomes increasingly evident.

Many biological systems scale in size and complexity so to exhibit a temporal network structure that emerges and self-organizes as it interacts with an environment. Living networks are everywhere from gene regulatory phases, protein interactions for physiology and metabolism, neural networks, onto animal groupings and social migrations. In particular, there may be structural features that result in homeostatic networks with specific higher-order statistics (multifractal spectrum). Here, we explore an opportunity for discovering universal laws which connect the structure of biological networks with their organism function. (Abstract excerpt)

Boogerd, Fred, et al, eds. Systems Biology: Philosophical Foundations. Amsterdam: Elsevier/Academic Press, 2007. A broad technical survey of theoretical approaches and methodologies.

Briscoe, James and James Sharpe. Genetics of Systems Biology. Current Opinion in Genetics and Development. 22/6, 2012. An introduction to an issue on this subject with articles such as The Importance of Geometry in Mathematical Models of Developing Systems, Evolution in Developmental Phenotype Space, and Towards a Statistical Mechanics of Cell Fate Decisions (search Ojalvo).

Caetano-Anolles, Gustavo, ed. Evolutionary Genomics and Systems Biology. New York: Wiley-Blackwell, 2010. This comprehensive survey by leading practitioners is a good example of the breadth, robustness and maturity of an historic, integral revision just beginning its course. Typical, notable papers are “The Role of Information in Evolutionary Genomics of Bacteria” by Antoine Danchin and Agnieszka Sekowska, “Genotypes and Phenotypes in the Evolution of Molecules” by Peter Schuster, and Eivind Almaas’ “Evolution of Metabolic Networks.”

Caetano-Anolles, Kelsey, et al. A Minimal Framework for Describing Living systems: A MultiDimensional View of Life Scales. Integrative & Comparative Biology. 61/6, 2021. Seven senior bioscholars post this Jumpstart Reintegrating Biology Vision Paper based on their 2020 meetings. As a result, a Scale-Invariant ECSI Framework (see Abstract) section spans from molecules, cells and organs to organisms, communities and ecosystems with a tabulated description for the emergent phases. A graphic depiction proceeds to view these evolutionary and metabolic occasions as a common, sewuential recurrence at each stage. Life’s informational quality is then said to be most important. A discussion about Unifying Life-science Research from Genomes to Phenomes to Bionomes wraps up going forward. Let us hope that this EarthWise phase of convergent synthesis with a universal code-like basis can illume a true Discovery Decade that peoples and planet so need.

The intricate complexity of biology has led to two general approaches. One is reductionism whence high-level whole systems emerge from simpler interactions at lower levels. Another is for specialists to investigate a specific hierarchical level. But these methods limit the scope and integration of knowledge and prevent a synoptic view of life. For this purpose, scale-invariant properties need to be identified that are present at all spatiotemporal phases. Here we will propose four resource aspects - energy, conductance, storage, and information (ECSI) – as a way to reintegrate and unify life science. (Abstract excerpt)

Carey, Nessa. The Epigenetics Revolution. New York: Columbia University Press, 2012. A popular entry by a British biologist with equal academic and industrial tenures about the realization, after its 20th century gene to trait basis, that much more is going on between molecular programs, actual organisms, and variegated environments. By a deft use of metaphor, DNA is not a mechanical blueprint, rather more like a play script or musical score. Romeo and Juliet, for example, has been staged and filmed in vastly different venues. DNA indeed acts a lot like a language. Epigenetics is then a two way communicative interaction that ultimately serves to produce life’s diverse phenotypes.

Cavagna, Andrea, et al. Physical Constraints in Biological Collective Behavior. Current Opinion in Systems Biology. 9/49, 2018. Systems scholars AC and Irene Giardina, Sapienza University of Rome, with Thierry Mora and Aleksandra Walczak, Sorbonne University, Paris, each of whom have joined this integrative quest for some years (search) post a Spring 2018 entry which might be its strongest fulfillment to date. As the quotes aver, by way of detailed studies of bird flocks or microbial colonies, along with similar observations across macro societal realms and micro active material depths, an epochal discovery comes into full view. At once, the “same phenomenal, iconic theory and principle” can be seen in generative effect at every instance and scale. This cosmic to culture, universe to us, vista which a worldwise intelligence has well quantified, then implies and requires an independent, universally exemplified, mathematical source. See also Dynamic Scaling in Natural Swarms by this group in Nature Physics (September 2017) for more about a statistical physics of renormalization and self-similarities.

Many biological systems require the coordinated operation of a large number of agents linked together by complex interactions in order to achieve their function reliably. Because of the complex relationship between individual laws and system-level behaviour, theory is needed to assess emergent phenomena which follow from logical or physical constraints. Here we illustrate this crucial role of theory through recent examples from the collective motion of bird flocks. In some cases abstract theoretical laws explain the emergence of some apparently surprising traits, without the need to invoke new assumptions. Conversely, quantitative theoretical predictions sometimes show that general mathematical and physical laws are incompatible with otherwise mundane observations, forcing us to reconsider our assumptions and leading us to discover new principles. (Abstract)

The perspective has inspired the whole field of living active matter and physics-based modeling of biological collectives. Many results on active systems at the micro-scale (cell tissues, bacterial colonies, microtubules) support the value of this approach. It turns out that the same theory can equally well predict the large scale behavior of living assemblies and inanimate active matter, which share the same fundamental properties. Recent findings on bird flocks and insect swarms indicate that these animal groups satisfy static and dynamic scaling laws: the large scale properties of the system under different conditions (number of individuals, density), can be described by a single master function. Laws of this kind are the phenomenological underpinning of universality in condensed matter materials, and suggest that the effective theoretical framework used for inanimate systems is also justified when looking at coherent animal groups at large scales. (50)

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