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

C. Our Own HumanVerse (Epi) Genomic Heredity

Koonin, Eugene and Artem Novozhilov. Origin and Evolution of the Universal Genetic Code. Annual Review of Genetics. 51/45, 2017. In this chapter, the National Center for Biotechnology Information biologist and a North Dakota State University mathematician can explain, from our late vantage, how life’s genetic program commonly holds for every organism. An interplay of chance and necessity from relatively random to this default, most successful mode thus becomes evident.

The standard genetic code (SGC) is virtually universal among extant life forms. Although many deviations from the universal code exist, particularly in organelles and prokaryotes with small genomes, they are limited in scope and obviously secondary. The universality of the code likely results from the combination of a frozen accident, i.e., the deleterious effect of codon reassignment in the SGC, and the inhibitory effect of changes in the code on horizontal gene transfer. The structure of the SGC is nonrandom and ensures high robustness of the code to mutational and translational errors. (Abstract excerpt)

So let us make a short list of well-established properties of the code and aspects of its evolution. * The code is effectively universal. Departures from code universality in extant organisms are minor. * The code is nonrandomly organized and is highly robust to errors. *Evolution of the code involved expansion from a limited set of primordial amino acids toward the canonical modern set. (57)

Krakauer, David. SFI @ 25: Very Few Cells Remain Unchanged. SFI Bulletin. Volume 24, 2009. A lead retrospective article about the Santa Fe Institute offers as an example of progress the nascent reinterpretation of genetic phenomena in terms of complex network systems. Such advances are then seen to contribute to its prime goal of the search for “general principles of complex, adaptive systems.” See also in this issue a longer article “The Complexity of the Gene Concept” by Krakauer and “Building Smart Groups” by Thomas Seeley

Traditionally, genetics was grounded in biochemistry, with a “disciplinary” approach of sequencing DNA and measuring gene activity. As the data increased, researchers catalogued the networks of interactions among molecules, and the genome became represented as a matrix of connections. At this point, questions of the stability and complexity of these networks became major concerns, forging a link with ecology, where researchers seek to understand the emergent properties of networks of interacting species. As the functional implications of these “ecological” patterns of activity started to surface, we began to see how the matrix of interactions could give rise to coherent patterns activity resulting from regular inputs to the system. Thus, the genome became a computational system, and questions of memory storage and information processing now dominate research. (1)

Kreplak, Jonathan, et al. A Reference Genome for Pea Provides Insight into Legume Genome Evolution. Nature Genetics. 51/9, 2019. Some 150 years after Gregor Mendel studied changes in pea plant height, pod and seed shape, flower position, color and more, forty-five geneticists posted in France, the Czech Republic, Australia, New Zealand, Germany, Canada, and the USA, a quite global group, post a comprehensive, graphic sequence.

Some 150 years after Gregor Mendel studied changes in pea plant height, pod and seed shape, flower position, color and more, forty-five geneticists posted in France, the Czech Republic, Australia, New Zealand, Germany, Canada, and the USA, a quite global group, post a comprehensive, graphic sequence.

Landenmark, Hanna, et al. An Estimate of the Total DNA in the Biosphere. PLoS Biology. Online July, 2015. With Duncan Forgan and Charles Cockell, University of Edinburgh, United Kingdom Centre for Astrobiology, researchers propose that it is now possible to quantify Earth’s flora and fauna endowment by way its genetic information content. The present biomass degree of “whole-organism genome analysis” is sufficient to be able to calculate a global value of “5.3 x 1031 megabases of DNA. It is said that such a novel view of natural and anthropogenic processes can aid their future sustainability. See also a NY Times notice on July 18 as Counting All the DNA on Earth by Rachel Nuwer.

Using available DNA sequencing and genome data, combined with large-scale surveys of biomass, we present an alternative way of quantifying and understanding biodiversity. This is accomplished by adopting an information view of biodiversity, in which the total amount of information in the biosphere is represented by the available amount of DNA. In this way, the biosphere can be visualised as a large, parallel supercomputer, with the information storage represented by the total amount of DNAand the processing power symbolised by transcription rates. In analogy with the Internet, all organisms on Earth are individual containers of information connected through interactions and biogeochemical cycles in a large, global, bottom-up network. (1)

We note that the approach that we propose here (and the analogy of supercomputers) does not necessarily imply a global, Gaia-like superorganism. We merely observe that ultimately allorganisms interact with each other and the environment. Thus, the information being processed in the biosphere is interlinked in a large mass of organisms, however one chooses to conceptualise this. It does not have to be considered as a single, self-regulating organism. The manner in which the total information in the biosphere is processed, and the degree to which it is coordinated and interlinked in feedback processes, is another matter, but one that could be investigated using an information-based approach. (2)

Lane, Nick and William Martin. The Energetics of Genome Complexity. Nature. 467/929, 2010. University College London, and Heinrich-Heine University geneticists propose a novel explanation of how cellular life originally prospered and grew together beyond rudimentary bacteria.

All complex life is composed of eukaryotic (nucleated) cells. The eukaryotic cell arose from prokaryotes just once in four billion years, and otherwise prokaryotes show no tendency to evolve greater complexity. Why Not? Prokaryotic genome size is constrained by bioenergetics. The endosymbiosis that give rise to mitochondria restructured the distribution of DNA in relation to bioenergetic membranes, permitting a remarkable 200,000-fold expansion in the number of genes expressed. This vast leap in genomic capacity was strictly dependent on mitochondrial power, and prerequisite to eukaryote complexity: the key innovation en route to multicellular life. (Abstract, 929)

The transition to complex life on Earth was a unique event that hinged on a bioenergetic jump afforded by spatially combinatorial relations between two cells and two genomes (endosymbiosis), rather than natural selection acting on mutations accumulated gradually among physically isolated prokaryotic individuals. Given the energetic nature of these arguments, the same is likely to be true of any complex life elsewhere. (933)

Ledford, Heidi. Riding the Crispr Wave. Nature. 531/136, 2016. A news report in a special section Crispr Everywhere about advances of this simple gene-splicing and editing technique with revolutionary potentials for genetic, medicinal and reproductive futures.

Levin, Michael and Christopher Martyniuk. The Bioelectric Code: An Ancient Computational Medium for Dynamic Control of Growth and Form. Biosystems. Online August, 2017. Tufts University and University of Florida biologists advance a broadly conceived project, with colleagues, to seek out and specify novel prescriptive means, agencies or informed forces which serve evolutionary organisms. The paper and task is imaginative and engaging as it elucidates more ways that life avails beside genes alone. As the second quote alludes, by way of computational analogies a doubleness of an independent, malleable program and resultant biological form and function can be perceived. See also, e.g., Endogenous Bioelectric Signaling Networks: Exploiting Voltage Gradients for control of Growth and Form by Leven, Giovanni Pezzulo and Joshua Finkelstein in Annual Review of Biomedical Engineering (19/353, 2017) and Physiological Inputs Regulate Species-Specific Anatomy During Embryogenesis and Regeneration by Kelly Sullivan, Maya Emmons-Bell, and Levin in Communicative & Integrative Biology (9/4, 2016) for more applications.

What determines large-scale anatomy? DNA does not directly specify geometrical arrangements of tissues and organs, and a process of encoding and decoding for morphogenesis is required. Moreover, many species can regenerate and remodel their structure despite drastic injury. The ability to obtain the correct target morphology from a diversity of initial conditions reveals that the morphogenetic code implements a rich system of pattern-homeostatic processes. Here, we describe an important mechanism by which cellular networks implement pattern regulation and plasticity: bioelectricity. All cells, not only nerves and muscles, produce and sense electrical signals; in vivo, these processes form bioelectric circuits that harness individual cell behaviors toward specific anatomical endpoints. We review emerging progress in reading and re-writing anatomical information encoded in bioelectrical states, and discuss the approaches to this problem from the perspectives of information theory, dynamical systems, and computational neuroscience. (Abstract)

This kind of generalized plasticity in servide to specific outcomes is closely related to a key insight that drove the development of the computer science revolution – the independence of hardware and software, and the ability to run the same software on different hardware, or obtain different behavior from the same hardware by changing the software. If bioelectric dynamics running on genome-specified ion channel complements in cells can be treated as a kind of software, the next revolution in biology could be likewise driven in part by the realization that we do not have to manipulate living systems at the level of their “machine code” (affecting specific molecules), but at the level of information – re-writing the encoded goal states and thus gaining a more top-down control over growth and form with myriad applications in biomedicine and robust technology. (15)

Lewontin, Richard. The Third Helix. Cambridge: Harvard University Press, 2000. As a response to the Human Genome hype, the renowned Harvard geneticist advises that DNA alone is not sufficient to specify even a folded protein much less an entire organism.

Liu, Shuming, et al. From Nucleosomes to Compartments: Physicochemical Interactions Underlying Chromatin Organization. Annual Review of Biophysics.. Volume 53, 2024. MIT system biologists add a latest chapter about life’s serial metabolic developments which can be traced to informative and topological genomic expressions. See also The Geometry of Chromatin by Subhash Kak at arXiv:2402.09408.

Chromatin organization plays a critical role in cellular function by regulating access to genetic information. However, its folding is hard to analyze due to a complex, multiscale nature. Advances have been made in vitro systems, individual nucleosomes, and the role of physicochemical forces in stabilization. But the resemblance between in vitro and in vivo chromatin conformations and internucleosomal interactions are subjects of debate. This article reviews experimental and computational studies which highlight intrinsic interactions between nucleosomes and their roles in chromatin folding. (Abstract).

Chromatin is a complex of DNA and protein found in eukaryotic cells.[1] The primary function is to package long DNA molecules into compact, denser structures. A nucleosome is a section of DNA that is wrapped around a core of proteins.

Longabaugh, William, et al. Computational Representation of Developmental Genetic Regulatory Networks. Developmental Biology. 283/1, 2005. Whereby ubiquitous complex system characteristics are similarly apparent in dynamic genomes. The authors then describe a freely available software package they have devised for their three-dimensional study: www.biotapestry.org.

Developmental genetic regulatory networks (GRNs) have unique architectural characteristics. They are typically large-scale, multilayered, and organized in a nested, hierarchy of regulatory network kernels, function-specific building blocks, and structural gene batteries. (1)

Madhanagopal, Bharath, et al. The unusual structural properties and potential biological relevance of switchback DNA. Nature Communications. 5/6636, 2024. A team of eight biogeneticists at SUNY Albany avail the latest instrumental methods and computational visualizations to come upon and illume a polar opposite version of the DNA helical coil. As a result, they can proceed with a retinue of novel properties.

Synthetic DNA motifs form the basis of nucleic acid nanotechnology. Here, we present a detailed characterization of switchback DNA, a globally left-handed structure composed of two parallel DNA strands. Compared to a conventional duplex, this form shows lower thermodynamic stability but exhibits enhanced biostability. Strand competition and strand displacement experiments show that component sequences have a preference for duplex complements. We hypothesize a potential role for switchback DNA as an alternate structure in sequences containing short tandem repeats which can open new avenues in biology and nanotechnology. (Excerpt)

In this work, we present a detailed characterization of a DNA motif called switchback DNA. Although the motif and its self-assembly into a lattice were recently reported, the biochemical and biophysical prop erties of this molecule are unknown. The impact of the unusual left-handed topology and parallel strand orientation on the physico-chemical properties of the motif is of potential interest in nucleic acid structure in general. We hypothesize that short tandem repeats may have the propensity to form switchback DNA as an alternate DNA structure and consider its potential role in biology and prospects in DNA nanotechnology. (2)

The RNA Institute at SUNY Albany is positioned to make significant contributions towards understanding the role of RNA in fundamental biological processes, developing RNA as a tool for science, and harnessing this knowledge to improve human health. The Institute brings together teams of researchers from multiple Departments and Universities with expertise in Biology, Bioinformatics, Chemistry, Engineering, Genetics, and Structural Biology.

Marijuan, Pedro. Information and the Unfolding of Social Life: Molecular-Biological Resonances Reaching Up to the Economy. BioSystems. 46/1, 1998. A universal convergence is noted from “cellular signaling systems and vertebrate nervous systems” to “entrepreneurial accounting systems.”

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