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A Sourcebook for the Worldwide Discovery of a Creative Organic Universe
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V. Life's Corporeal Evolution Develops, Encodes and Organizes Itself: An EarthWinian Genesis Synthesis

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

Moya, Andres, et al. Goethe’s Dream. EMBO Reports. 10/S1, 2009. In this issue on Systems Biology and the Virtual Physiological Human, University of Valencia biologists begin by reminding that Immanuel Kant (1724-1804) defined organisms as having “an intrinsic purpose, because they are self-organized in such a way that every part is a function of the whole.” Reference is then made to Johann von Goethe (1749-1832) whose holistic vista led him to write that while a living entity can be dissected into elements, its life only exists as an integral entity. In accord, this is our worldwide 21st century project to complete by systematically reassembling all the molecules, microbes, organs, anatomies and physiologies.

Muller, Gerd. Evo-devo as a Discipline. Minelli, Alessandro and Giuseppe Fusco, eds. Evolving Pathways: Key Themes in Evolutionary Developmental Biology. Cambridge: Cambridge University Press, 2008. The University of Vienna biologist introduces another volume that advances the 21st century reunion of evolution and embryology. In this 2009 Darwin year, Muller notes that the real Charles was not a sterile selectionist as he has been turned into. Rather he was immersed in the Naturphilosophe of his day distinguished by a recapitulationist view of life’s development, in some real way akin to embryonic gestation. Muller goes on to add that we today need to factor in the evident presence of an inherent, constant self-organizing, modularity.

Inherency refers to the fact that through the inclusion of evo-devo into evolutionary theory there is a shift of focus from the external and contingent to the internal and generic. Whereas historical contingency is a significant element in the standard evolutionary framework, accounting for the lawful dependence on conditions that involve a large component of chance, inherency is something that will always happen because the potentiality is immanent to the system and can actually only be inhibited. (21) It posits that the causal basis for phenotypic evolution resides not merely in population genetics events or, for that matter, in gene regulatory evolution, but in the inherent features of evolving developmental systems. (21-22)

Muller, Gerd. EvoDevo Shapes the Extended Synthesis. Biological Theory. 9/2189, 2014. The University of Vienna biologist and president of the European Society for Evolutionary Developmental Biology (Google for 2014 Euro Evo Devo) introduces an issue on imperative 21st century revisions as life’s embryogeny and gestation is again factored in. Today a robust quantification is in place from proactive genomes across sequential emergent stages to language and societies. An especial entry is Connecting the Dots: Anatomical Network Analysis in Morphological EvoDevo by Diego Rasskin-Gutman and Borja Esteve-Altava (search). See also Multilevel Causation and the Extended Synthesis by Max Martinez and Maurizio Esposito, Universal Grammar and Biological Variation: An EvoDevo Agenda for Comparative Biolinguistics by Antonio Benitez-Burraco and Cedric Boeckx, and The Role of the Morphogenetic Field by Sheena Tyler.

Muller, Gerd. Where EvoDevo Goes Beyond the Modern Synthesis. www.ishpssb.org. We highlight this abstract from the Summer 2007 conference of the International Society for the History, Philosophy, and Social Studies of Biology held at the University of Exeter. Google ISHPSSB and go to Conference Program for abstracts of some 200 papers. By way of Eva Jablonka, Linda Van Speybroeck, Beckett Sterner, Richard Watson, and related presentations, who bring in epigenetic, complex system, nested network, and other features, one might notice a novel, inclusive evolutionary synthesis ‘in the air’ whose orthogenesis brings forth our human observation.

And inherency, informed through the work on the generic physical and epigenetic properties of developmental systems, refers to the fact that the inclusion of EvoDevo into evolutionary theory represents a shift of explanatory weight from the external and contingent to the internal and generic. Whereas historical contingency is a key element in the standard neoDarwinian framework, accounting for the lawful dependence on conditions that involve a large component of chance, inherency is something that will always happen because the potentiality is immanent to the system and can actually only be inhibited. Inherency is the buzz word for the important new focus introduced by EvoDevo in locating the causality of the evolution of morphological form not in external selection and population genetic events, but in the dynamics of interaction between genes, cells, and tissues, each endowed with their own physical and functional properties and dependent upon interactions with the environment. (Gerd Muller)

Muller, Gerd and Stuart Newman. The Innovation Triad: An EvoDevo Agenda. Journal of Experimental Zoology. 304B/487, 2005. While debate rages over teaching the textbook version of Darwinism in schools, a quite different, much broadened theory and synthesis is apparent in the primary journals of evolutionary biology. As the quotes testify, genetic drift by itself will not result in new animal form. An understanding of the innate self-organizing propensities of dynamic genomic systems, as they interact with various epigenetic conditions such as permitted internal topologies and fluid external environments, now provide the elusive explanation of how new organisms occur. But an even greater adjustment from a chance evolution bereft of impetus or goal results. When the presence of such generative propensities and preferred pathways is admitted, a directional “inherency” is then evident. So a “natural genesis” seems indeed in the air and literature, which this website seeks to document and communicate.

We argue that the mechanisms of innovation and their phenotypic results – novelty – can only be properly addressed if they are distinguished from the standard evolutionary themes of variation and adaptation,…..We point out that an inclusion of developmental systems properties into evolutionary theory represents a shift of explanatory emphasis from the external factors of natural selection to the internal dynamics of developmental systems, complementing adaptation with emergence, and contingency with inherency. (487) In adaptation, the motive force resides in natural selection acting on an underlying substrate – heritable variation – the necessary boundary condition. In innovation, natural selection represents the boundary condition, whereas the properties of developmental systems provide the motive force for the ensuing change. (499)

Inherency is a second general property of evolving systems. It complements the contingency emphasized by the neo-Darwinian side of evolutionary theory. Whereas historical contingency denotes the lawful dependency of evolutionary change on earlier chance, inherency represents the tendency to organize and change along preferred routes, leading, unless inhibited, to predictable outcomes. Emergence and inherency represent those generative principles that are missing from the standard evolutionary framework and which are now in the process of being incorporated into a more complete theory by EvoDevo. (499)

Nadeau, Joseph and Aimee Dudley. Systems Genetics. Science. 331/1015, 2011. Within the scientific revolution to reconceive every field by way of complex network dynamics, Institute for Systems Biology, Seattle, researchers pursue their theoretical application to active genetic phenomena. As a consequence, the historic shift in understanding genomes from particulate nucleotides to equally real dynamical interrelations, indeed as DNA/AND, is much underway. View the ISB website noted above and click on Nadeau Group or Dudley Group for more info.

In contrast to the networks of molecular and physical interactions that dominate the field of systems biology, systems genetics focuses on networks of interactions between genes and traits, as well as between traits themselves. (1015) an essential but not yet fully exploited application of systems genetics is the inference of higher-order functionality in complex systems from patterns of covariation among underlying molecular and physiological phenotypes. (1015)

Neher, Richard and Boris Shraiman. Statistical Genetics and Evolution of Quantitative Traits. Reviews of Modern Physics. 83/4, 2011. Early in the 2010s, UC Santa Barbara, Kavli Institute for Theoretical Physics scope out approaches to technically achieve a vital, necessary unity of a material basis and physiological replication.

The distribution and heritability of many traits depends on numerous loci in the genome. In general, the astronomical number of possible genotypes makes the system with large numbers of loci difficult to describe. Multilocus evolution, however, greatly simplifies in the limit of weak selection and frequent recombination. In this limit, populations rapidly reach quasilinkage equilibrium in which the dynamics of the full genotype distribution, including correlations between alleles at different loci, can be parametrized by the allele frequencies. This review provides a simplified exposition of the concept and mathematics of QLE which is central to the statistical description of genotypes in sexual populations. (Abstract)

Newman, Stuart. Animal Egg as Evolutionary Innovation: A Solution to the “Embryonic Hourglass” Puzzle. Journal of Experimental Zoology: Molecular and Developmental Evolution. 316/467, 2011. By referring to original self-organizing “physical” processes, the New York Medical College biologist can go on to elucidate nature’s innate propensity for the formation of ovular cells. After citing a commonality across oviparous fauna of initial eggs, the “embryonic hourglass” in biology is defined as “a morphologically conserved intermediate state of development in vertebrates before they go on to assume their class-specific character,” say fish, bird or mammal. An explanatory resolve of this dilemma, and of life’s whole gestation, is achieved by the introduction of “dynamic pattern modules.” Not yet fully defined, these molecular assemblies appear to play an intermediary role, as if a translator, between self-organizing forces and generative cell to cell interactions and signaling functions. But reading the engaging paper, one gets a sense of an intrinsically fertile, egg producing, embryonic cosmos.

The evolutionary origin of the egg stage of animal development presents several difficulties for conventional developmental and evolutionary narratives. If the egg's internal organization represents a template for key features of the developed organism, why can taxa within a given phylum exhibit very different egg types, pass through a common intermediate morphology (the so-called “phylotypic stage”), only to diverge again, thus exemplifying the embryonic “hourglass”? Moreover, if different egg types typically represent adaptations to different environmental conditions, why do birds and mammals, for example, have such vastly different eggs with respect to size, shape, and postfertilization dynamics, whereas all these features are more similar for ascidians and mammals? Here, I consider the possibility that different body plans had their origin in self-organizing physical processes in ancient clusters of cells, and suggest that eggs represented a set of independent evolutionary innovations subsequently inserted into the developmental trajectories of such aggregates. (Abstract, 467)

I first describe how “dynamical patterning modules” (DPMs) associations between components of the metazoan developmental-genetic toolkit and certain physical processes and effects may have organized primitive animal body plans independently of an egg stage. Next, I describe how adaptive specialization of cells released from such aggregates could have become “proto-eggs,” which regenerated the parental cell clusters by cleavage, conserving the characteristic DPMs available to a lineage. Then, I show how known processes of cytoplasmic reorganization following fertilization are often based on spontaneous, self-organizing physical effects (“egg-patterning processes”: EPPs). I suggest that rather than acting as developmental blueprints or prepatterns, the EPPs refine the phylotypic body plans determined by the DPMs by setting the boundary and initial conditions under which these multicellular patterning mechanisms operate. Finally, I describe how this new perspective provides a resolution to the embryonic hourglass puzzle. (Abstract, 467)

Nielsen, Jens. Systems Biology of Metabolism. Annual Review of Biochemistry. 86/11.1, 2017. A Chalmers University of Technology, Sweden, biologist provides a good entry to this holistic approach which blends top down syntheses with bottom up molecular and cellular components and functions.

Metabolism is highly complex and involves thousands of different connected reactions; it is therefore necessary to use mathematical models for holistic studies. The use of mathematical models in biology is referred to as systems biology. In this review, the principles of systems biology are described, and two different types of mathematical models used for studying metabolism are discussed: kinetic models and genome-scale metabolic models. The use of different omics technologies, including transcriptomics, proteomics, metabolomics, and fluxomics, for studying metabolism is presented. Finally, the application of systems biology for analyzing global regulatory structures, engineering the metabolism of cell factories, and analyzing human diseases is discussed. (Abstract)

Noble, Denis. A Biological Relativity View of the Relationships between Genomes and Phenotypes. Progress in Biophysics and Molecular Biology. 111/2-3, 2013. For an issue on “Conceptual Foundations of Systems Biology,” the Oxford University physiologist and innovative leader in this movement continues his advocacy of the equally present dynamic interconnections between all the nucleotide and molecular components. In accord with James Shapiro, Eva Jablonka, and others, by this view a whole vista of expanded “epi-omics” (my term) is being opened. “Biological relativity,” from Nottale and Auffray (search), denotes that organisms have multilevel, creative dynamics which are not ruled by any one scalar stage. See also “A Theory of Biological Relativity: No Privileged Level of Causation” in Interface Focus (6/2, 2011), and “Biophysics and Systems Biology” (2010) noted above.

This article explores the relativistic principle that there is no privileged scale of causality in biology to clarify the relationships between genomes and phenotypes. The idea that genetic causes are primary views the genome as a program. Initially, that view was vindicated by the discovery of mutations and knockouts that have large and specific effects on the phenotype. But we now know that these form the minority of cases. Many changes at the genome level are buffered by robust networks of interactions in cells, tissues and organs. The ‘differential’ view of genetics therefore fails because it is too restrictive. An ‘integral’ view, using reverse engineering from systems biological models to quantify contributions to function, can solve this problem. The article concludes by showing that far from breaking the supervenience principle, downward causation requires that it should be obeyed. (Abstract)

Noble, Denis. Biophysics and Systems Biology. Philosophical Transactions of the Royal Society A. 368/1125, 2010. After a state of the art survey, the emeritus Oxford University Chair of Cardiovascular Physiology offers his well honed view of organisms as upwardly and downward multifactorial and multilevel entities. Drawing on physical “scale relativity” theories of Laurent Nottale and Charles Auffray (search), it is advised that a certain “privileged level of causation” is not supported. As a result, novel, enhanced appreciations of “genetic programs” and a systems evolution can accrue. See also in this journal his earlier “Genes and Causation” (366/3001, 2008) and 2012 papers elsewhere on this site.

Biophysics at the systems level, as distinct from molecular biophysics, acquired its most famous paradigm in the work of Hodgkin and Huxley, who integrated their equations for the nerve impulse in 1952. The modern field of computational biology has expanded rapidly during the first decade of the twenty-first century and, through its contribution to what is now called systems biology, it is set to revise many of the fundamental principles of biology, including the relations between genotypes and phenotypes. Evolutionary theory, in particular, will require re-assessment. To succeed in this, computational and systems biology will need to develop the theoretical framework required to deal with multilevel interactions. While computational power is necessary, and is forthcoming, it is not sufficient. We will also require mathematical insight, perhaps of a nature we have not yet identified. (Abstract)

Noble, Denis. The Music of Life. Oxford: Oxford University Press, 2006. The renowned Professor of Cardiovascular Physiology at University College London offers lyrical insights into systems biology guided by musical metaphors - but seemingly without a composer since score and melody must co-evolve. An insightful chapter then finds a deep correspondence between genetic realms and human language. Similar to many Chinese characters based on a small number of prime cases, a genome uses a few regulatory modules which control how multitudes of DNA strands are expressed. Natural selection then acts upon a preferential result of such heretofore unknown “invisible general principles.” See a book review by Eric Werner in Science for August 10, 2007.

Systems biology is where we are moving to. Only, it requires a quite different mind-set. It is about putting together rather than taking apart, integration rather than reduction. (xi)

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