V. Life's Corporeal Evolution Develops, Encodes and Organizes Itself: An Earthtwinian Genesis Synthesis

B. Systems Biology Unites: EvoDevo, Genomes, Cells, Networks, Symbiosis, Homology, Inherency

Walhout, Marian, et al, eds. Handbook of Systems Biology. Cambridge, MA: Academic Press, 2012. A comprehensive volume with a new emphasis on –omics and networks by contributors such as Alfred Barabasi, Erik Davidson, Reka Albert, and Andreas Wagner,. Typical chapters are Interactome Networks, Transcriptional Network Logic, Genotype Networks and Evolutionary Innovations, and Reconstruction of Genome-Scale Metabolic Networks. Each entry comes with extensive references.

Westerhoff, Hans and Bernhard Palsson. The Evolution of Molecular Biology into Systems Biology. Nature Biotechnology. 22/10, 2004. An historical perspective from the 1930’s which took two paths – a main emphasis on discrete macromolecules culminating in the human genome sequence, and a lesser, relational notice of self-organizing and systemic interactions.

We have agreed that contemporary systems biology has an historical root outside mainstream molecular biology, ranging from basic principles of self-organization in nonequilibrium thermodynamics, through large-scale flux and kinetic models to ‘genetic circuit’ thinking in molecular biology. “Systems thinking’ differs from ‘component thinking’ and requires the development of new conceptual frameworks. (1251)

Westerhoff, Hans, et al. Systems Biology: The Elements and Principles of Life. FEBS Letters. 583/24, 2011. this Nobel Symposium on Systems Biology issue, Manchester Centre for Integrative Systems Biology, The University of Manchester, and Netherlands Institute for Systems Biology, University of Amsterdam researchers contribute to on-going efforts to situate, define, contrast, and move forward with this 21st century endeavor.

Systems Biology has a mission that puts it at odds with traditional paradigms of physics and molecular biology, such as the simplicity requested by Occam’s razor and minimum energy/maximal efficiency. By referring to biochemical experiments on control and regulation, and on flux balancing in yeast, we show that these paradigms are inapt. Systems Biology does not quite converge with biology either: Although it certainly requires accurate ‘stamp collecting’, it discovers quantitative laws. Systems Biology is a science of its own, discovering own fundamental principles, some of which we identify here. (Abstract)

Witzany, Gunther. Natural Genome Editing from a Biocommunicative Perspective. Biosemiotics. 4/3, 2011. As the Abstract below conveys, the prolific biophilosopher continues to advance this approach and school that moves beyond neoDarwinism to appreciate gene sequences in a way as an informative “language-like text.”

Natural genome editing from a biocommunicative perspective is the competent agent-driven generation and integration of meaningful nucleotide sequences into pre-existing genomic content arrangements, and the ability to (re-)combine and (re-)regulate them according to context-dependent (i.e. adaptational) purposes of the host organism. Natural genome editing integrates both natural editing of genetic code and epigenetic marking that determines genetic reading patterns. As agents that edit genetic code and epigenetically mark genomic structures, viral and subviral agents have been suggested because they may be evolutionarily older than cellular life.

This hypothesis that viruses and viral-like agents edit genetic code is developed according to three well investigated examples that represent key evolutionary inventions in which non-lytic viral swarms act symbiotically in a persistent lifestyle within cellular host genomes: origin of eukaryotic nucleus, adaptive immunity, placental mammals. Additionally an abundance of various RNA elements cooperate in a variety of steps and substeps as regulatory and catalytic units with multiple competencies to act on the genetic code. Most of these RNA agents such as transposons, retroposons and small non-coding RNAs act consortially and are remnants of persistent viral infections that now act as co-opted adaptations in cellular key processes.

Woese, Carl. A New Biology for a New Century. Microbiology and Molecular Biology Reviews. 68/2, 2004. The leading theorist of microbial taxonomy finds biological science to have reached in its course an epochal turning point and paradigm shift. The necessary 20th century approach of identifying the molecular, genetic and microbial components has fulfilled its task. But this results in an incomplete, mechanical view of nature. To move forward, a diametric integral vista is called for whereby life’s innate evolutionary emergence is expressed by the new sciences of self-organizing complexity. And it is just this revolution that Natural Genesis is trying to report and convey. Woese’s important paper is also noted in Part V, A Quickening Evolution, and Part VI, Microbial Colonies.

The molecular cup is now empty. The time has come to replace the purely reductionist “eyes-down” molecular perspective with a new and genuinely holistic, “eyes-up,” view of the living world, one whose primary focus is on evolution, emergence, and biology’s innate complexity. (175) And it is becoming increasingly clear that to understand living systems in any deep sense, we must come to see them not materialistically, as machines, but as (stable) complex, dynamic organization. (176)

Biologist now need to reformulate their view of evolution to study it in complex dynamic-systems terms. (180) Translationally produced proteins, multicellular organisms, and social structures are each the result of, emerge from, fields of interaction when the latter attain a certain degree of complexity and specificity. (180)

Wolkenhauer, Olaf and Jan-Hendrik Hofmeyr. An Abstract Cell Model that Describes the Self-Organization of Cell Function in Living Systems. Journal of Theoretical Biology. 246/461, 2007. University of Rostock, Germany and University of Stellenbosch, South Africa mathematical system biologists explain the self-organizing coordination of cell function, as most distinguished by its bounded closure.

The principal aim of systems biology is to search for general principles that govern living systems. We develop an abstract dynamic model of a cell, rooted in Mesarović and Takahara's general systems theory. In this conceptual framework the function of the cell is delineated by the dynamic processes it can realize. We abstract basic cellular processes, i.e., metabolism, signalling, gene expression, into a mapping and consider cell functions, i.e., cell differentiation, proliferation, etc. as processes that determine the basic cellular processes that realize a particular cell function. We then postulate the existence of a ‘coordination principle’ that determines cell function. These ideas are condensed into a theorem: If basic cellular processes for the control and regulation of cell functions are present, then the coordination of cell functions is realized autonomously from within the system. (461)

Inspired by Robert Rosen's notion of closure to efficient causation, introduced as a necessary condition for a natural system to be an organism, we show that for a mathematical model of a self-organizing cell the associated category must be cartesian closed. Although the semantics of our cell model differ from Rosen's (M,R)-systems, the proof of our theorem supports (in parts) Rosen's argument that living cells have non-simulable properties. Whereas models that form cartesian closed categories can capture self-organization (which is a, if not the, fundamental property of living systems), conventional computer simulations of these models (such as virtual cells) cannot. Simulations can mimic living systems, but they are not like living systems. (461)

Yu, Haiyuan and Mark Gerstein. Genomic Analysis of the Hierarchical Structure of Regulatory Networks. Proceedings of the National Academy of Sciences. 103/14724, 2006. Genome systems are found to employ a consistent network motif by which to achieve viable translation. This is said to be the same organization which is present in human societies. Another contribution to a natural genesis that recycles a common pattern and process from atom to cosmos.

A fundamental question in biology is how the cell uses transcription factors (TFs) to coordinate the expression of thousands of genes in response to various stimuli. The relationship between TFs and their target genes can be modeled in terms of directed regulatory networks. These relationships, in turn, can be readily compared with commonplace “chain-of-command” structures in social networks, which have characteristic layouts. (14724) In general, our results show that there is a pyramid-shaped hierarchical structure in regulatory networks, which is well organized in a clearly nonrandom manner. The decision making scheme in this hierarchy is a cogitation-like multistep process. (14730)

Zeiltinger, Julia, et al. Perspective on recent developments and challenges in regulatory and systems genomics. arXiv:2411.04363.. arXiv:2411.04363. Eight biogeneticists across the USA from California to Wisconsin to Georgia onto Norway and Mexico cover expansive frontier approaches in this field with an emphasis on deeper learning and computer techniques.

Predicting how genetic variation affects phenotypic outcomes at the organismal, cellular, and molecular levels requires deciphering the cis-regulatory code. In this review, we describe how cis-regulatory elements are mapped and how their sequence rules can be interpreted with neural networks. We point out current gaps along with limitations and benchmarking challenges of computational methods. We discuss newly emerging technologies such as spatial transcriptomics, and outline strategies for creating a general model of the cis-regulatory code that is broadly applicable across cell types and individuals.
(Ezcerpts)

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