IV. Ecosmomics: Independent Complex Network Systems, Computational Programs, Genetic Ecode Scripts

C. Our Own HumanVerse (Epi) Genomic Heredity

Snyder, Michael and Mark Gerstein. Defining Genes in the Genomics Era. Science. 300/258, 2003. Now that genomes, the entire genetic coding system for a certain organism, are becoming sequenced and transcribed, a new concept of what a gene is results. Rather than particulate in kind, they are more like “a complete chromosomal segment responsible for making a functional product.” (258)

Snyder, Michale, et al. Perspectives on ENCODE. Nature. 583/693, 2020. 21 coauthors from the ENCODE Project Consortium including Mark Gerstein post a latest status report as this Encylopedia of DNA Elements proceeds apace to sequence whole genomes for an expanding array of species.

The Encylopedia of DNA Elements (ENCODE) Project launched in 2003 with the long-term goal of developing a comprehensive map of functional elements in the human genome. These included genes, biochemical regions associated with gene regulation (for example, transcription factor binding sites, open chromatin, and histone marks) and transcript isoforms. The marks serve as sites for candidate cis-regulatory elements (cCREs) that may serve functional roles in regulating gene expression1. The project has been extended to model organisms, particularly the mouse. In the third phase of ENCODE, nearly a million and more than 300,000 cCRE annotations have been generated for human and mouse, respectively, and these have provided a valuable resource for the scientific community.

Stenseth, Nils, et al.. Gregor Johann Mendel and the Development of Modern Evolutionary Biology. PNAS. 119/30, 2022. A Gregor Johann Mendel and Modern Evolutionary Biology Special Feature herein to mark the 200th anniversary of his birth is introduced by NS, University of Oslo, Leif Andersson, Uppsala University and Hopi Hoekstra, Harvard University. Some other contents are Mendel and Darwin by Andrew Berry and Janet Browne, the “New Synthesis” by Nicholas Barton and Three Problems in the Genetics of Speciation by Selection by Dolph Schluter and Loren Rieseberg.

This year we celebrate the 200th anniversary of the birth of Gregor Johann Mendel, who discovered the missing component of Darwin’s evolutionary theory, the genetic mechanism of trait inheritance. The eight articles in this Special Feature collection cover various aspects of Mendel’s life, his work, and his contribution to science, with a special focus on his impact in evolutionary biology. In this introductory paper, we provide the context for the eight papers, as well as summarize how Mendel’s work has contributed to the development of modern evolutionary biology.

Stoltzfus, Arlin. Mutation Biased Adaptation in a Protein NK Model. Molecular Biology and Evolution. 23/10, 2006. A University of Maryland biologist argues that genetic change is not an accidental variant that passively awaits selection. Rather, new gene configurations act as an “immanent directional orienting factor” upon evolutionary pathways. See also Stoltzfus’ Mutationism and the Dual Causation of Evolutionary Change in Evolution and Development (8/3, 2006) and Google his name.

Thus, it is of interest to consider the possibility that biases or nonrandomness in the rate of origin of new variants by mutation (and more generally, by mutation and altered development) are a general cause of nonrandomness in evolution, a possibility that cuts across traditional scientific disputes over selection versus drift, the Modern Synthesis versus the Neutral Theory, and morphological versus molecular evolution. (1853)

Stotz, Karola. Experimental Philosophy of Biology. Studies in History and Philosophy of Science. 40/2, 2009. A University of Sydney philosopher contributes to the 21st century project to reinvent and redefine genetic phenomena beyond older particulate “genes” so as to include the equally present layers of interactive, relational networks

In this vision the ‘gene’ is relieved of its unrealistic and mystical status as the sole embodiment of life. Instead, genes become prosaic ways to classify the template capacity of certain parts of the genome, a capacity that must be interpreted through a process of gene expression to yield any determinate result. Because of this limited and very context-dependent capacity, the gene is also stripped of its place as the sole unit of inheritance. (237) Inheritance is not embodied in mystical preformations of the phenotype but in the reproduction of the necessary factors of development that will self-organize to reproduce a similar developmental life cycle. Life is not situated in genes but in the particular organization of biomolecules that enables the system to maintain itself by reconstituting its own components from the template capacity in the genome, constructing the environmental factors necessary for this to occur, and ultimately reproducing copies of itself. (237)

Stotz, Karola. The Ingredients for a Postgenomic Synthesis of Nature and Nurture. Philosophical Psychology. 21/3, 2008. An introduction by the University of Sydney scholar to papers from a March 2007 Indiana University symposium on “Reconciling Nature and Nurture in Behavior and Cognition Research.” The shifting genetic paradigm from discrete “programs” to an “interactive” epigenetic context, which involves both the cellular organism and its external environment, is under review, and evokes a sense of molecular “letters and words” and their parsed usage in descriptive sentences and paragraphs. As a growing number of other fields realize, a dynamic dialogue of essential script and contingent evolutionary and developmental editing goes on. Other notable authors herein include Eva Jablonka, Paul Griffiths, Jason Scott Robert, and Edouard Machery.

In other words, the more complex an organism, the more complex the expression of its limited number of coding sequences….what is of particular importance during development is not the existence of some genes but their differential time- and tissue-dependent expression. In the last two decades development has become equated with differential gene expression, but what is hidden behind this equation is the complex network of molecules other than DNA (such as proteins and metabolites), cellular structures, three-dimensional cellular assemblages, and other higher-level structures that control or are otherwise involved not only in the differential expression of genes but in a wide range of other developmental processes decoupled from the direct influence of DNA sequences. (363)

Strohman, Richard. The Coming Kuhnian Revolution in Biology. Nature Biotechnology. 15/3, 1997. A notable statement of the shift underway from a determinism of particulate genes to an embryonic development due to informed dynamic systems similar to neural networks.

The theory is in trouble because it insists on locating the driving force solely in random mutations. An alternative theory of evolution that emphasizes the importance of nonrandom (epigenetic) changes during development could explain the problems now being encountered by evolutionary theory. (195) The cell is starting to look more like a complex adaptive system rather than a factory floor of robotic gene machines, and that is well and good….Many of us are guessing at some kind of complex adaptive system theory that can embrace discontinuous change at all levels of life’s organization. (197)

Sweatt, David. The Emerging Field of Neuroepigenetics. Neuron. 80/3, 2013. In a special Neuroscience Retrospective, a University of Alabama neurobiologist provides a past and future survey of this expansion of genetic phenomena beyond just point nucleotides. The admission that both genes and environment reciprocally interact and cross-contribute then requires a major rethinking such as “What Roles Do Epigenetic Mechanisms Play in Complex Human Diseases of the Nervous System?” and “Are Acquired Epigenetic Marks Transmitted Across Generations?” with regard to an “epigenome code.” See also in this issue The New Science of Mind and the Future of Knowledge by Nobel laureate Eric Kandel.

Over the past 25 years, the broad field of epigenetics and, over the past decade in particular, the emerging field of neuroepigenetics have begun to have tremendous impact in the areas of learned behavior, neurotoxicology, CNS development, cognition, addiction, and psychopathology. However, epigenetics is such a new field that in most of these areas the impact is more in the category of fascinating implications as opposed to established facts. In this brief commentary, I will attempt to address and delineate some of the open questions and areas of opportunity that discoveries in epigenetics are providing to the discipline of neuroscience. (Abstract)

Only infrequently do scientific discoveries force the recasting of a centuries-long philosophical debate. However, over the last 25 years, and indeed largely over the last decade, the emerging field of neuroepigenetics has necessitated the reformulation of the fundamental existential question of nature versus nurture. Based on recent discoveries in the broad field of epigenetics, it no longer makes sense to debate nature versus nurture. There is no longer a mechanistic dichotomy between nature and nurture (or genes and environmental experience, as is the more modern phrasing). Rather, it is now clear that there is a dynamic interplay between genes and experience, a clearly delineated and biochemically driven mechanistic interface between nature and nurture. That mechanistic interface is epigenetics. (624)

Trieu, Tuan, et al. Hierarchical Reconstruction of High-Resolution 3D Models of Large Chromosomes. Nature Scientific Reports. 9/4971, 2019. University of Missouri bioinformatic scientists Tuan Trieu (Vietman), Oluwatosin Oluwadare (Nigeria), and Jianlin Cheng (China) come together in mid America where they are developing better ways to visualize whole genome structures, as the paper illustrates. An improved image quality is achieved by a novel algorithm which can fully reveal these complex nucleotide packages

Tsuchiya, Masa, et al. Emergent Self-Organized Criticality in Gene Expression Dynamics. PLoS One. June, 2015. In a contribution that can exemplify the current global frontiers of discovery, systems biologists from Japan and Latvia show by theory and experiment that even genomes can be found to exhibit this complex phenomena as everywhere else. The subtitle is Temporal Development of Global Phase Transition Revealed in a Cancer Cell Line. BY these insights a novel 21st century conception of genetic form and activity is achieved, which is then seen as similar to neural network computations. By a turn toward a physical substrate, a further explanation is offered by way of statistical physics and thermodynamics. To reflect on this technical paper, by the mid 2010s the composite, also dynamically self-organizing, worldwide science seems to be reaching an emergent phase of finding a universal repetition of the same common system from universe to human.

Thus, it is natural to abandon a ‘single molecule’ level of explanation when considering self-organization into discrete ‘phenotypic states’ as stable attractor states in the gene-expression landscape. The emergence of a favored ‘globally convergent’ solution that attracts the system dynamics overcomes the problem of stochastic fluctuations related to a gene-by-gene regulation paradigm. (2)

To interpret biological regulation within the framework of physics, we must eliminate the need for Maxwell’s demons, i.e., intelligent agents that actively drive the system toward a desired goal. An attractor-based global dynamics under thermodynamically open conditions for all living matter enables regulation without the need for such intelligent agents. Then, seeing a cell dynamically controlling genome-wide expression, (we ask) What is the ‘driving force’ that attracts the entire system toward a few preferred global states, thus making the genome act as a single integrated system? Statistical mechanics postulates that energetically preferred configurations of a system arise through the satisfaction of relationships among its constituent parts subjected to external constraints. These correlations shape the state space of the cell as an ‘epigenetic landscape’. (2-3)

In the preceding paragraphs we observed genomes acting ‘as a whole’: the same transition point accounts for all the critical domains albeit with a different ‘amount of displacement’. If chromatin structural transitions are the material counterparts of such coherent dynamics, we can expect a corresponding typical arrangement of genes for critical states along the chromosomes. Three distinct states (super-, near- and sub-critical) in mRNA expression were revealed based on the theoretical framework of modern theoretical physics from a non-equilibrium self-organizing standpoint. (20)

Notably, this tells us that an ensemble behavior of barcode genes through on-off phase transitions on chromosomes has a similar dynamic ensemble behavior to a cascade of the on-off nerve firing bursts in neuronal networks. This indicates a non-trivial similarity between the coherent network of genomic DNA transitions and neural networks; coherent networks based on on/off switching of barcodes genes in SOC may imply the existence of rewritable self-organized memory in the genome acting as genome computing. (23)

Van Nimwegen, Erik. Scaling Laws in the Functional Content of Genomes. Trends in Genetics. 19/9, 2003. More thoughts on the perception of common natural principles at work.

In this article I show that, for many high-level functional categories, the number of genes in each category scales as a power-law of the total number of genes in the genome. The occurrence of such scaling laws….suggests that the exponents of the observed scaling laws correspond to universal constants of the evolutionary process. (479)

Van Speybroeck, Linda, et al. Epi-Geneticization: Where Biological and Philosophical Thinking Meet. Fagot-Largeault, Anne, et al, eds. The Influence of Genetics on Contemporary Thinking. Berlin: Springer, 2007. In a volume that explores how changing views of genomes work their way into social discourse, Ghent University philosophers survey the epic revolution from 20th century discrete deoxyribonucleic acid molecules, (of course necessary first had to find and name all the pieces). Much more is now seen to be going on which involves a whole array of interconnective network, hierarchical, modular, and informational processes and patterns. By these lights, genomic systems are suffused by and exemplify the same self-organizational properties found throughout nature. But a further conceptual step is then invited, we add. A clear implication would be that these universal, independent propensities that serve organic development and behaviors ought to be appreciated as truly “genetic” in kind. In such regard, they take on a guise and role as a cosmic parental code, with both an original parental independence while being instantiated everywhere in developmental evolution, universe and human in a 21st century temporal, unfolding gestation.

Via the notion of context, a means is found to transcend a reductionist view on genes as sole organizers of both biological organisms and biological knowledge. Within an epigenetic framework, genes no longer stand for inviolable molecular atoms ‘causing’ the organism, but rather for temporarily relatively stable units which take form within a biological system, i.e. a dynamic self-organizing system in which the partaking factors interpret one another, and through this interpretation construct each others functional meaning. (125-126)

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