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

B. Our Own HumanVerse (Epi) Genomic Heredity

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.

Rzhetsky, Andrey and Shawn Gomez. Birth of Scale-Free Molecular Networks and the Number of Distinct DNA and Protein Domains per Genome. Bioinformatics. 17/10, 2001. The same invariance evident throughout the natural realm is equally present in dynamic genetic systems.

Salthe, Stan. The Natural Philosophy of Ecology. www.nbi.dk/~natphil/salthe/natphilecol.2001. An essay on the need to rediscover an original unity in nature in order to find an “intelligible picture of the world.” So conceived, evolution is most of all the “irreversible accumulation of historical information.”

Sandoval-Motta, Santiago, et al. The Human Microbiome and the Missing Heritability Problem. Frontiers in Genetics. Online June 13, 2017. Universidad Nacional Autónoma de México researchers contribute to this on-going concern since 2008 when it was realized that the copious Human Genome Project data results could not yet fully explain organisms. We cited an extended Abstract in regard. A Google of the MH thtle phrase will get more hits, this paper is another instance of expansive inputs much beyond nucleotides alone.

The “missing heritability” problem states that genetic variants in Genome-Wide Association Studies (GWAS) cannot completely explain the heritability of complex traits. Traditionally, the heritability of a phenotype is measured through familial studies using twins, siblings and other close relatives, making assumptions on the genetic similarities between them. When this heritability is compared to the one obtained through GWAS for the same traits, a substantial gap between both measurements arise with genome wide studies reporting significantly smaller values. Several mechanisms for this “missing heritability” have been proposed, such as epigenetics, epistasis, and sequencing depth. However, none of them are able to fully account for this gap in heritability. In this paper we provide evidence that suggests that in order for the phenotypic heritability of human traits to be broadly understood and accounted for, the compositional and functional diversity of the human microbiome must be taken into account.

This hypothesis is based on several observations: (A) The composition of the human microbiome is associated with many important traits, including obesity, cancer, and neurological disorders. (B) Our microbiome encodes a second genome with nearly a 100 times more genes than the human genome, and this second genome may act as a rich source of genetic variation and phenotypic plasticity. (C) Human genotypes interact with the composition and structure of our microbiome, but cannot by themselves explain microbial variation. (D) Microbial genetic composition can be strongly influenced by the host's behavior, its environment or by vertical and horizontal transmissions from other hosts. Therefore, genetic similarities assumed in familial studies may cause overestimations of heritability values. We also propose a method that allows the compositional and functional diversity of our microbiome to be incorporated to genome wide association studies. (Abstract)

Sansom, Roger. The Connectionist Framework for Gene Regulation. Biology & Philosophy. 23/4, 2008. The Texas A&M University philosopher finds a useful affinity to exist between this neuroscience approach, aka parallel distributed processing and neural networks, and molecular genomic systems. His own website cites an MIT Press forthcoming book: Ingenious Genes: How Gene Regulation Networks Evolve to Control Ontogeny. One more citation of nature’s consistent employ, under various terms and emphasis, of the same complex dynamics at each and every phase and instance.

Seringhaus, Michael and Mark Gerstein. Genomics Confounds Gene Classification. American Scientist. November-December, 2008. As noted herein, the intensive genome sequencing of human, primate, and other species have resulted in a total revision of what constitutes a gene. In this report, Yale University geneticists first review the last 70 years to illustrate a steady morphing from discrete molecules to a growing notice of systemic, repetitive networks, along with many epigenetic influences. In this bioinformatics age, how “genes” and their functions are defined, named, and classified is of much importance. But a leap of the author’s work is to perceive its deep affinity with the formative phase and current operative format of the World Wide Web. Common parallels occur by way of ontologies which gather distributed annotations and intelligence. One involves proteins, the other web pages. Might it then be imagined through an emergence from word to flesh to word that the globally collaborative Internet could be in some way genetic in kind?

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