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

C. Our Own HumanVerse (Epi) Genomic Heredity

Pearson, Helen. What is a Gene? Nature. 441/399, 2006. The burst of genome sequencing is causing a major revision in the definition of what a gene is. No longer beads on a string, it is more like a DNA information package, which involves RNA, and whose protein codes have no clear beginning or end.

Piatogorsky, Joram. Gene Sharing and Evolution. Cambridge: Harvard University Press, 2007. The Chief of the Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, quite engaged at the forefront of genetic research, discusses the on-going revision and redefinition of the nature of genes and their many activities. As an example of original multitasking, one gene can produce a polypeptide (a protein string of amino acids) with several optional biochemical functions. These novel insights and properties contribute to the systems biology project to articulate such contextual dynamic networks that discrete genes are contained within.

Although gene sharing refers specifically to multiple molecular uses of an individual polypeptide, the modern “gene” in gene sharing is an interactive, differentially expressed gene that challenges the investigator to see in how many ways it can enlarged through the functions of its polypeptide rather that how it might be subdivided into an elementary unit, as was the goal of investigators in the classical and neoclassical concepts of the gene. (53) Networks transform molecular biology to “modular” biology and link the rules of biology to many different disciplines, including statistical physics, engineering, the Internet, ecosystems, and social interactions. (196)

Pigliucci, Massimo. Genotype-Phenotype Mapping and the End of the ‘Genes as Blueprint’ Metaphor. Philosophical Transactions of the Royal Society B. 365/557, 2010. A paper in a dedicated issue on “Phenotypic Plasticity in Development and Evolution.” As long as an evolutionary burden remains that nothing beyond accident and selection is going on, a grand revision, here actually added to by one of the main players, (see Pigliucci & Muller, eds. Evolution – the Extended Synthesis, May 2010 from MIT Press) can not yet be appreciated. We are advised once more that the textbook stage of “bean-bag genetics” is over, superseded by nonlinear developmental encodings between information and individual in the guise of robust modular networks with “computational” activities.

Portin, Petter. The Elusive Concept of the Gene. Hereditas. 146/3, 2009. In a paper noted by the journal as the most cited, a University of Turku, Finland geneticist provides a succinct summary, as the three quotes aver, of the 21st century revolution from molecular determinations to “interlaced networks” across nested scales stretching in a reciprocal way from genome to organism and environment. A “gene” is no longer a separate, fixed entity, rather entire genotypes are complicated webworks of complex, heritable components. Nucleotide sequences thus become “quantitative collections of binary information” applied in a variety of instances, depending on the organismic context. And to add, while reading about such genes and genomes, one is struck by their similarity to words in a sentence and paragraph, with a meaning dependent on the message being conveyed.

In recent years geneticists have witnessed many significant observations which have seriously shaken the traditional concept of the gene. These specifically include the facts that (1) the boundaries of transcriptional units are far from clear; in fact, whole chromosomes if not the whole genome seem to be continuums of genetic transcription, (2) many examples of gene fusion are known, (3) likewise many examples of so-called encrypted genes are known in the organelle genomes of microbial eukaryotes and in prokaryotes, and (4) in addition to the structure of the gene, its functional status can also be inheritable, and, further, (5) epigenetic extra-genomic modes of inheritance, called genetic restoration, seem to be a rather common phenomenon, meaning that organisms can sometimes rewrite their DNA on the basis of RNA messages inherited from generations past. (Abstract)

I will briefly review these observations and discuss the difficulties of defining the gene, and then formulate a new view, which is called the relational or systemic concept of the gene. It has to be noted that genes assume their information content characteristics in the Shannonian sense as nucleotide sequences of DNA (or RNA). However, on the basis of this we cannot say anything about their information content in the semantic sense. The semantic information content of genes is context-dependent. Genes namely assume their biochemical characteristics usually only within living cells, their developmental characteristics only within living organisms, and their evolutionary characteristics only within populations of living organisms. (Abstract, 112)

Accordingly, it can be said that the science of genetics is gradually moving away from a reductionistic way of thinking towards a more holistic – or better said – systemic way of thinking, which takes the whole of the organism and its parts into consideration at the same time. In fact, it is not possible to really understand a given whole without understanding its constituent parts nor really understand the parts of a given biological system – be it a gene, cell, individual, population or ecosystem – without understanding it as a total integrated whole. (115)

Portin, Petter and Adam Wilkins. The Evolving Definition of the Term “Gene.”. Genetics. 205/4, 2017. University of Turku, Finland and Humboldt University, Germany biologists (search each) first survey past takes on this “unit of inheritance” from before and after the 1950s molecular DNA helix and through to major 21st century revisions. In this current phase which gives equal import to “gene regulatory networks (GRN),” a new sense of nodal nucleotide and interlinked reciprocities, aka genome-wide association studies (GWAS), has come forth. As the quote alludes, we may view one more exemplary presence of a universal complementarity of particulate and integrative modes.

The conceptual consequences of viewing individual genes not as autonomous actors, but as interactive elements or outputs of networks are profound. For one thing, it becomes relatively easy to think about the nature of genetic background effects in terms of the structure of gene regulatory nets. While much of the thinking of the 20th century about genes was based on the premise that the route from gene to phenotype was fairly direct, and often deducible form the nature of the gene product, the network perspective envisages far more complexity and indirectness of effects. In general, the path from particular genes to specific phenes is long, and the role of many gene products seems to be the activation or repression of the activities of other genes. (1360)

Qui, Jane. Unfinished Symphony. Nature. 441/143, 2006. The codons in our now sequenced genome are orchestrated by an overlaying “epigenetic” code, which researchers are just tuning in to.

Rando, Oliver and Kevin Verstrepen. Timescales of Genetic and Epigenetic Inheritance. Cell. 128/4, 2007. One cannot underestimate the scope of this revolution in our understanding of heredity and evolution. While classic theory says phenotypic variety arises from random mutations independent of selective pressures, the latest research finds that organisms have evolved mechanisms to influence the timing or genomic location of heritable variation. In a revival of “directed mutagenesis” from the 1980’s, cells seem to exhibit a biased behavior in favor of successful variants to changing environmental stresses. By these lights, the views of Darwin, and especially of Lamarck, that life evolves in a self-guiding manner so as to maximize its survivability are said to deserve new notice. (See also Bernstein, Bradley, et al. The Mammalian Epigenome in the same issue)

We now finally turn to the idea that organisms may orchestrate specific, nonrandom heritable changes in themselves in response to appropriate conditions. (665)

Rea, Thomas, et al. Complex Adaptive Systems and the Genetic Analysis of Plasma HDL-Cholesterol Concentration. Perspectives in Biology and Medicine. 49/4, 2006. Together with Christine Brown and Charles Sing, all from the University of Michigan, another example of the conceptual shift in genetics whereof the old gene model of isolated particles is set aside in favor of dynamically self-organizing genomic systems. Rather than deterministic programs, typical CAS features of multiple interacting agents (apolipoproteins, receptor and membrane proteins, the genes that encode them, and various lipid classes), which form modular domains, and nonlinearly emergent phenotypes are being found. The authors conclude that a new, integrative, humanist ‘natural philosophy’ is implied.

On the other hand, living organisms are better understood as complex adaptive systems characterized by multiple participating agents, hierarchical organization, extensive interactions among genetic and environmental effects, nonlinear responses to perturbation, temporal dynamics of structure and function, distributed control, redundancy, compensatory mechanisms, and emergent properties. (491)

Richards, Stephen. It’s More than Stamp Collecting: How Genome Sequencing can Unify Biological Research. Trends in Genetics. 31/7, 2015. In accord with how 2010s genome reading capabilities are wholly revising paleontology studies, a Baylor College of Medicine, Human Genome Sequencing Center, geneticist proposes to advance the life sciences by a similar emphasis and synthesis. Just as paleogenomics is achieving, scientists are beginning to employ these novel potentials across the Metazoan flora and fauna kingdoms. Going forward, we ought to recognize and employ this revolutionary approach via comparative orthologies and ontologies from arthropods to anthropopods (my word). With proper foresight, the establishment of a sufficiently complete spatial and temporal genome reference library should be of great value for ecological sustainability.

The availability of reference genome sequences, especially the human reference, has revolutionized the study of biology. However, while the genomes of some species have been fully sequenced, a wide range of biological problems still cannot be effectively studied for lack of genome sequence information. Here, I identify neglected areas of biology and describe how both targeted species sequencing and more broad taxonomic surveys of the tree of life can address important biological questions. I enumerate the significant benefits that would accrue from sequencing a broader range of taxa, as well as discuss the technical advances in sequencing and assembly methods that would allow for wide-ranging application of whole-genome analysis. Finally, I suggest that in addition to ‘big science’ survey initiatives to sequence the tree of life, a modified infrastructure-funding paradigm would better support reference genome sequence generation for research communities most in need. (Abstract)

Ridley, Matt. Genome. New York: HarperCollins, 1999. A lively chronicle of the twenty-three chromosomes of the human genetic makeup as viewed through the book of life metaphor.

In the beginning was the word. The word proselytized the sea with its message, copying itself unceasingly and forever. The word discovered how to rearrange chemicals so as to capture little eddies in the stream of entropy and make them live. The word transformed the land surface of the planet from a dusty hell to a verdant paradise. The word eventually blossomed and became sufficiently ingenious to build a porridgy contraption called a human brain that could discover and be aware of the word itself. (12)

Ridley, Matt. Nature via Nurture. New York: HarperCollins, 2003. The British science writer explains the current revolution in our understanding of genes and their relation to behavioral experience. The old view of particulate molecules that determine traits, unaffected by external influence, is being replaced by a conception of genetic systems as dynamic networks constantly responding to an organism’s environment in a two way dialogue. For human beings, a mutual drive between larger brains and complex culture and is encoded in and expressed by ones corresponding genetic information.

Ridley, Matt. The DNA behind Human Nature: Gene Expression and the Role of Experience. Daedalus. Fall, 2004. A succinct update based on the latest genetics research of how the molecular code is composed and operates. In this regard, the British science writer draws upon a literary analogy to reach a significant conclusion. We now know that the same 30,000 or so genes are found throughout the animal kingdom, from humans to worms, with a quite minute difference between us and chimpanzees. But if genotypes are appreciated as letters and words in sentences and paragraphs, it is their content, i.e. how these genes are expressed, that specifies the phenotype organism.

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