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

C. Our Own HumanVerse (Epi) Genomic Heredity

Mattick, John. RNA Out of the Mist. Trends in Genetics. 19/3, 2023. Looking back 50 years, the veteran University of New South Wales geneticist reviews some 50 years of research studies as twists, turns and progress, in which he participated, toward current appreciations of the vital functions played by this major nucleotide.

RNA has long been regarded as the intermediate between genes and proteins. It was a surprise then to discover that eukaryotic genes are mosaics of mRNA sequences with by large tracts of transcribed but untranslated sequences, and that multicellular organisms express long ‘intergenic’ and antisense noncoding RNAs (lncRNAs). The emerging picture is that most lncRNAs are the products of genetic loci termed ‘enhancers’, which marshal generic effector proteins to their sites of action to control cell fate decisions during development. (Excerpt)

Maynard Smith, John and Eors Szathmary. The Orgins of Life. Oxford: Oxford University Press, 1999. A popular update of the authors’ 1995 treatise on major nested, informed transitions, which is reviewed more in A Genesis Evolutionary Synthesis, and by 2010 has become a major structural contribution to this imminent advance.

McGillivray, Patrick, et al. Network Analysis as a Grand Unifier in Biomedical Data Science. Annual Review of Biomedical Data Science. Vol. 1, 2018. In this new Annual Review edition, a team of Yale University biochemists, bioinformaticians, and geneticists including Mark Gerstein show how common network processes and topologies can similarly be applied with benefit to genomic and physiological realms. Sections such as Networked Systems are at the Core of Human Biology, Making Sense of Complexity in Biomolecular Networks, Network Motifs, Logic, and Stability, and Prediction using Machine Learning and Neural Networks via text and graphic displays offer a state of the art tutorial for later 2010 advances. By so doing, once again a nascent sense of a universal recurrence across molecule, organelle, cell, organ, entity, and population phases, as illustrations depict, of the same intricate dynamics becomes evident.

Biomedical data scientists study many types of networks, ranging neural nets to those created by molecular interactions. However an issue of interpretation exists. Here we show that molecular biological networks can be read in several straightforward ways. First, we divide a network into smaller components with individual pathways and modules. Second, we compute global statistics describing the network as a whole. Third, we can compare networks which can be within the same context (e.g., gene regulatory networks) or cross-disciplinary (e.g. governmental hierarchies). By studying the relationships between variants in networks, we can begin to interpret many common diseases, such as cancer and heart disease. (Abstract excerpt, edits)

Meadows, Jennifer and Kerstin Lindblad-Toh. Dissecting Evolution and Disease Using Comparative Vertebrate Genomics. Nature Reviews Genetics. 18/624, 2017. We cite this entry by Uppsala University and MIT/Harvard researchers (KLT credits below) to show how a worldwide biological science can achieve by theory and technique a retrospective reconstruction of the genetic endowment of prior evolutionary species. A full page graphic Figure 1 is entitled A Snapshot of Vertebrate Genome Sequencing Projects as they proceed from fish and reptiles to birds, mammals and onto human beings. Might one via a woman’s bicameral faculty ask and imagine what this whole scenario could be on its own? What kind of procreative ecosmos evolves to a sentient, collaborative global species able look back and do this?

With the generation of more than 100 sequenced vertebrate genomes in less than 25 years, the key question arises of how these resources can be used to inform new or ongoing projects. In the past, this diverse collection of sequences from human as well as model and non-model organisms has been used to annotate the human genome and to increase the understanding of human disease. In the future, comparative vertebrate genomics in conjunction with additional genomic resources will yield insights into the processes of genome function, evolution, speciation, selection and adaptation, as well as the quantification of species diversity. In this Review, we discuss how the genomics of non-human organisms can provide insights into vertebrate biology and how this can contribute to the understanding of human physiology and health. (Abstract)

Kerstin Lindblad-Toh is a professor in comparative genomics at Uppsala University and the director of Science for Life Laboratory Uppsala. As also the scientific director of vertebrate genome biology at the Broad Institute (Harvard/MIT) she is responsible for the 29 Mammals Project to annotate the human genome for functional constraint, as well as a large number of vertebrate genome projects. These include the dog disease-mapping group which has developed several SNP chips used to identify canine disease genes. The Science for Life Laboratory has a vision of being an internationally leading center that develops, applies, and provides access to large-scale technologies for molecular biosciences, with a focus on translational medicine and on evolutionary and systems biology. (KLT website)

Meinesz, Alexandre. How Life Began: Evolution’s Three Geneses. Chicago: University of Chicago, 2008. Reviewed in The Symbiotic Cell and noted here for this cogent quote of how well literature terms describe genetic activity.

To describe the characteristics of these modes of transmitting information, with their errors, mixings, and exchanges, scientists use printing terms: replication, transcription, recombination, transposition, translocation, reshuffling, inversion. These words apply to parts of the “book” (in this case, the nuclei) that constitutes the totality of the information of life: chapters (or, chromosomes), pages (parts of chromosomes), paragraphs (genes), lines (sequences of nucleotides), words (triplets of nucleotides), and letters (nucleotides). (106)

Miranda-Dominguez, Oscar, et al. Heritability of the Human Connectome. Network Neuroscience. 2/2, 2018. In an issue on New Trends in Connectomics, Oregon Health and Science University and Emory University behavioral neuroscientists propose a familial “connectotype” akin to a bodily phenotype to likewise represent a person’s cerebral endowment. In a similar way, ancestral histories can then be traced.

Misteli, Tom. Beyond the Sequence: Cellular Organization of Genome Function. Cell. 128/787, 2007. By the National Cancer Institute, NIH, researcher, a good review of the state of genetic rethinkings at the time from this novel whole systems perspective.

The similarities in spatial and temporal properties of the various nuclear processes indicate that the organizational principles involved in their biogenesis are universal. (790) It thus appears that compartmentalization of nuclear processes, likely via self-organization, into well-defined yet dynamically malleable sites is one of the fundamental principles of organizing genome function in vivo. (790)

Mitchell, Melanie. Complexity: A Guided Tour. Oxford: Oxford University Press, 2009. Reviewed more in A Cosmic Code, we note for still another view of genomes distinguished not by discrete molecules, but dynamical, communicative networks – which then, by inference, ought to be rightly seen as “genetic” in kind.

The complexity of living systems is largely due to networks of genes rather that the sum of independent effects of individual genes. (275) In the old genes-as-beads-on-a-string view, as in Mendel’s laws, genes are linear - each gene independently contributes to the entire phenotype. The new, generally accepted view, is that genes in a cell operate in nonlinear information-processing networks, in which some genes control the actions of other genes in response to changes in the cell’s state – that is, genes do not operate independently. (275-276)

Moghadam, S. Arbabi, et al. A Search for the Physical Basis of the Genetic Code. Biosystems. May, 2020. We cite because this entry by University of Alberta biophysicists including Jack Tuszynski discuss several ways that life’s genomic endowment can be rooted in and given a deeper substantial, innately fertile basis.

DNA contains the genetic code, which provides complete information about the synthesis of proteins in every living cell. Each gene encodes for a corresponding protein but most of the DNA sequence is non-coding. In addition to this non-coding part of the DNA, there is another redundancy, namely a multiplicity of DNA triplets (codons) corresponding to code for a given amino acid. In this paper we investigate possible physical reasons for the coding redundancy, by exploring free energy considerations and abundance probabilities as potential insights. (Abstract)

Moore, David. The Developing Genome: An Introduction to Behavioral Epigenetics. New York: Oxford University Press, 2015. With everything that constitutes the nature and activity of genomes undergoing a whole-scale expansive renovation, a Pitzer College psychologist provides a good overview of the project. This late, historic revision harking back to Lamarck and Cuvier now has genetic phenomena spreading far beyond nucleotides to parental, personal, social, and environmental influences.

Morange, Michel. Genome as a Multipurpose Structure Built by Evolution.. Persepctives in Biology and Medicine.. 57/1, 2015. In a special issue on The Changing Concept of the Gene, the French biologist and philosopher reviews the history of genetics as a “progressive discovery of the complexity of the genome” from biomolecular nucleotides to gene regulatory networks to an integral system lately taking on epigenetic functions.

Morowitz, Harold. Phenetics, A Born Again Science. Complexity. 8/1, 2003. Another report of a major paradigm shift in biology from random, particulate genes to a systems integration of a phenotypic genetics which can generate metabolic networks.

If biology is governed by a hierarchy of phenetic laws, then replaying the tape (of life) might lead to a rather similar outcome particularly at the unicellular level. Our task as biologists is then to search for these laws rather than focusing on the thousand billion elements of sequence that must characterize the biosphere. (13)

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