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IV. Ecosmomics: Independent, UniVersal, Complex Network Systems and a Genetic Code-Script Source

B. Our Own HumanVerse (Epi) Genomic Heredity

Katz, Laura. Genomes: Epigenomics and the Future of Genome Sciences. Current Biology. 16/23, 2006. A Smith College biologist surveys and documents the nascent revolution which finds much more is going on beyond molecular genes. A definition for “epigenetics” might be the transmission of information not coded in DNA sequences from cell to daughter cell or from generation to generation. In this regard, as the quote broaches, instead of a direct route from genotype to phenotype, many intermediate functions get into the act, which changes everything.

Epigenomics encompasses genome-wide analyses of the growing list of epigenetic phenomena – such as DNA methylation, chromosome inactivation, non-Mendelian inheritance and programmed genome rearrangements – that are found across the tree of life. (R996)

Kaye, Alice and Wyeth Wasserman. The Genome Atlas: Navigating a New Era of Reference Genomes. Trends in Genetics. January, 2021. Children's Hospital Research Institute, University of British Columbia scholars conceive, specify and finesse some better ways to display and access all manner of burgeoning genetic data bases. Our further interest is their strong employ of a ready cross-affinity between genomic scriptomes and literate, library-like textual analogies.

The reference genome serves two distinct purposes within the field of genomics. First, it provides a persistent structure against which findings can be reported, which then allows for universal knowledge exchange between users. Second, it reduces the computational costs and time required to process genomic data by creating a software scaffold that can be relied upon. Here, we posit that current efforts to extend the linear reference to a graph-based structure will face a trade-off between comprehensiveness and computational efficiency. In this article, we explore how the reference genome is used and suggest an alternative structure, The Genome Atlas (TGA), to fulfill the bipartite role of the reference genome. (Abstract)

Box 1. The Library Analogy Consider a library of books that represents our collective knowledge regarding the human genome. In place of the words of a story, a book contains a DNA sequence that is an allele or a stretch of immutable nucleotide. The complete diploid genome of an individual can be constructed through two series of books read in a specific order. Each book has two sets of information associated with it: (i) meta-information (e.g., author, publisher, or genre); and (ii) the text within. This divide extends to searching for books, or looking within a specific book. The utilization of meta-information for feature identification and the functional implications of the differences between genomes or populations of genomes form ‘knowledge exchange’ with regards to a reference genome.

Keller, Evelyn Fox. The Century of the Gene. Cambridge: Harvard University Press, 2000. A case against the limited, erroneous fixation on particulate genetic molecules and for an expanded, dynamical system of epigenetic expression. An extensive update "Beyond the Gene," with coauthor David Harel, can be found online at PloS One, (11/e1231, 2007), which argues for a new language and definition of a "gene."

Keller, Evelyn Fox. The Postgenomic Genome. Sarah Richardson and Hallam Stevens, eds.. Postgenomics: Perspectives on Biology after the Genome. Durham, NC: Duke University Press, 2015. In this chapter, the MIT science philosopher, historian, and feminist scholar, renown for her biography of the Nobel geneticist Barbara McClintock, provides a succinct review of the latest whole scale reimaginations of genome phenomena. As the quotes convey, no longer a passive registry, an holistic (epi)genomic organ acts in (re)active engagement with all manner of environmental influences. Other chapters such as The Polygenomic Organism by John Dupre and a summary by the editors well express this 2010s revolution.

Despite all the changes the gene concept has undergone, many of even the most recent formulations retain the view of these entities (and hence of genomes) as effectively autonomous formal agents, containing the blueprint for an organisms life – that is, all of the biological information needed to build and maintain a living organism. But I am claiming that current research in genomics leads to a different picture, and it does so by focusing attention on features that have been missing from our conceptual framework. In addition to providing information required for building and maintaining an organism, the genome also provides a vast amount of information enabling it to adapt and respond to the environment in which it finds itself, as indeed it must if the organism is to develop more or less normally and to survive more or less adequately. I am proposing that today’s genome, the postgenomic genome, looks more like an exquisitely sensitive reaction (or response) mechanism – a device for regulating the production of specific proteins in response to the constantly changing signals it receives from its environment – than it does the pregenomic picture of the genome as a collection of genes initiating causal chains leading to the formation of traits. (25)

The reconceptualization of the genome that I propose (from agentic to reactive) allows us – indeed obliges us – to abandon the dichotomies between genetics and environment, and between nature and culture, that have driven so much fruitless debate, for so many decades. If much of what the genome “does” is to respond to signals from its environment, then the bifurcation of the developmental influences into the categories of genetic and environmental makes no sense. Similarly, if we understand the term “environment” as including cultural dynamics, neither does the division of biological from cultural factors. We have long understood that organisms interact with their environments, that interactions between genetics and environment, between biology and culture, are crucial to making us what we are. What research in genomics shows is that, at every level, biology itself is constituted by those interactions – even at the level genetics. (29)

Kepes, Francois. On the Transcription-based Solenoidal Model of Chromosomes: Epigenomics of Molecular Networks. Bioinformatics: Algorithms, Structures and Statistics Workshop. December 2005, . From a meeting which took place at the Ecole Polytechnique, Palaiseau, France, papers accessible via Google, e.g. Kepes+epigenomics. This certain work is one example deep in the literature of the growing recognition of “self-organizational principles” which serve to generate chromosome systems and cellular nuclear architecture. But such a major addition to and revision of evolutionary biology has not yet reached a paradigm shift, which this website hopes to facilitate.

Kirby, K. The Informational Perspective. BioSystems. 46/1, 1998. An overview of a special issue wherein 26 papers survey the programmatic aspects of self-organizing systems which appear with fractal similarity from biochemical reactions to the Internet.

Koonin, Eugene. CRISPR: A New Principle of Genome Engineering Linked to Conceptual Shifts in Evolutionary Biology. Biology & Philosophy. 34/9, 2019. The National Center for Biotechnology Information, Bethesda biotheorist and author writes an invited paper for a special issue to broadly appreciate these multi-faceted genetic advances and abilities. In so doing, it is broached that biomolecular mechanisms for actual Lamarckian epigenetic effects seem to be evident. After an introduction Philosophy of CRISPR-Cas by Thomas Pradeau, the edition adds commentaries such as by Eva Jablonka who leavens with a “quasi” Lamarckian model. Other entries cite its potential for easy palliative editing, the specter of Jean Baptiste is opposed by Ford Dollitle, Emily Parke, Sam Woolley, et al. A balanced view may be Sophie Veigl’s paper A Use/Disuse Paradigm.

The CRISPR-Cas systems of bacterial and archaeal adaptive immunity have become a household name among biologists and the general public by the unprecedented success of new generation of genome editing tools utilizing Cas proteins. However, the fundamental biological features of CRISPR-Cas are of no lesser interest and have major impacts on our understanding of the evolution of antivirus defense, host-parasite coevolution, self versus non-self discrimination and mechanisms of adaptation. CRISPR-Cas systems present the best known case in point for Lamarckian evolution, i.e. generation of heritable, adaptive genomic changes in response to encounters with external factors, in this case, foreign nucleic acids.

CRISPR-Cas systems employ multiple mechanisms of self versus non-self discrimination but, as is the case with immune systems, are costly because autoimmunity cannot be eliminated completely. Analysis of the evolutionary connections of Cas proteins reveals multiple contributions of mobile genetic elements (MGE) to the origin of various components of CRISPR-Cas systems, The shared features of adaptive defense systems and MGE, namely the ability to recognize and cleave unique sites in genomes, make them ideal candidates for genome editing and engineering tools. (Abridged Abstract)

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)

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