RNA-mediated physics, chemistry, and molecular epigenetics

Genetics and Genomics May 11-12, 2016

Published on 3 May 2016  See the full size poster displayed on Figshare.com

Abstract:

Olfaction and the innate immune system link energy as information from the epigenetic landscape to the physical landscape of supercoiled DNA. The sun’s biological energy is the source of the information that links angstroms to ecosystems via physics, chemistry, and molecular epigenetics.

RNA-mediated protein folding chemistry and amino acid substitutions link the anti-entropic quantized energy of sunlight from the virucidal effects of ultraviolet (UV) light to healthy longevity via biophysically-constrained energy-dependent hydrogen-atom transfer in DNA base pairs in solution and cell type differentiation.

Biomarkers link energy-dependent differences in base pairs and amino acid substitutions to biosignatures across the healthy life span. RNA-mediated amino acid substitutions also reveal the increasing complexity of interactions among cell types as pathology progresses. For comparison, successful reproduction links energy from supercoiled DNA to protection of all organized genomes from virus-driven energy theft and pathology.

This model links the sun’s biological energy from top-down causation in microbes to the most recent model of bottom-up gene activation and cell type differentiation in vertebrates. Citations to extant literature provide examples of what is currently known about how ecological variation leads to biophysically constrained cell type differentiation in the context of nutritional epigenetics and Precision Medicine, which clearly link metabolic networks and genetic networks to pharmacogenomics.

Content:

Physics:  Quantum theory links ecological variation and food odors from the supply of specific nutrients to climate change and stress-effected differences in human brain development. [1-3]

[1] A quantum theory for the irreplaceable role of docosahexaenoic acid in neural cell signalling throughout evolution

[2] Climate warming is predicted to reduce omega-3, long-chain, polyunsaturated fatty acid production in phytoplankton

[3] Maternal choline intake alters the epigenetic state of fetal cortisol-regulating genes in humans

Chemistry:  Quantized energy from the sun links ultraviolet (UV) light on contact with water to hydrogen-atom transfer in DNA base pairs in solution and RNA-mediated DNA repair via amino acid substitutions. [4-9]

Cryo-electron tomography (cryo-ET) [10-11] and cryo-electron microscopy (cryo -EM) [12] link electron density from angstroms to ecosystems in the context of transgenerational epigenetic inheritance of energy-dependent RNA-amino acid substitutions and/or virus-driven pathology. For example ~10 amino acids surround the Asn154 glycosylation site of the Zika virus. Remarkably similar findings were confined to one generation of mass die-offs in a species of fish. [13]

Transgenerational effects of the Zika virus link the nutrient-dependent RNA-mediated immune system and the physiology of reproduction in vertebrates to supercoiled DNA, which typically prevents virus-driven entropy in all organized genomes. [14-17]

Outside the context of the non-linear links from physics and chemistry to biologically-based cause and effect, the differences in the Zika virus and all living organisms are typically placed into the context of neo-Darwinian evolution via master genes that drift to fixation in the host population. [18-19]

For contrast, everything known about nutrient energy-dependent cell type differentiation links viruses in gut microbes from metabolic networks and genetic networks to invertebrate and vertebrate biodiversity. [20-23]

[4] Electrolytes induce long-range orientational order and free energy changes in the H-bond network of bulk water

[5] Serial interactome capture of the human cell nucleus

[6] Pado, a fluorescent protein with proton channel activity can optically monitor membrane potential, intracellular pH, and map gap junctions

[7] Dissipation Bounds All Steady-State Current Fluctuations

[8] Physicists prove energy input predicts molecular behavior

[9] Metabolic Regulation of Histone Post-Translational Modifications

[10] Architecture of the symmetric core of the nuclear pore

[11] Structural diversity of supercoiled DNA

[12] The 3.8 Å resolution cryo-EM structure of Zika virus

[13] Characterization of a Novel Orthomyxo-like Virus Causing Mass Die-Offs of Tilapia.

[14] Force distribution in a semiflexible loop

[15] Mammalian elongation factor 4 regulates mitochondrial translation essential for spermatogenesis

[16] The Bull Sperm MicroRNAome and the Effect of Fescue Toxicosis on Sperm MicroRNA Expression

[17] Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk

[18] From Mosquitos to Humans: Genetic Evolution of Zika Virus

[19] Comprehensive Transcriptome Profiles of Streptococcus mutans UA159 Map Core Streptococcal Competence Genes

[20]  A Tunable Mechanism Determines the Duration of the Transgenerational Small RNA Inheritance in C. elegans

[21] Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota

[22] Wolbachia Blocks Viral Genome Replication Early in Infection without a Transcriptional Response by the Endosymbiont or Host Small RNA Pathways

[23] Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes

Molecular epigenetics

It has become clear to all serious scientists that nutrient-dependent microRNA flanking sequences link RNA-mediated amino acid substitutions to  ecological adaption via protection against virus-driven energy theft, which links a single amino acid substitution to increased virulence of viruses. [24 -28]

The role of the nutrient-dependent substitution of the achiral amino acid glycine in position six of the gonadotropin releasing hormone (GnRH) decapeptide, established GnRH secretion as the link from the gut microbes of invertebrates to all vertebrate biologically-based cause and effect. GnRH secretion links hormone-organized and hormone-activated behaviors from invertebrates to vertebrates via olfaction and the innate immune system. [29]

This representation of epigenetically-effected genome organization can be compared to theories about mutations in the context of facts about RNA-mediated amino acid substitutions and energy-dependent cell type differentiation. The nutrient-dependent amino acid substitutions differentiate all cell types in all individuals of all genera via what is currently known about biophysically constrained RNA-mediated protein folding chemistry.

[24] Identification of Amino Acid Substitutions Supporting Antigenic Change of Influenza A(H1N1)pdm09 Viruses;

[25] Nutrient-dependent/pheromone-controlled adaptive evolution: a model

[26] The phylogenetic utility and functional constraint of microRNA flanking sequences;

[27] Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity

[28] Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization

[29] From Fertilization to Adult Sexual Behavior

Microbiomes, Metabolism, Mitochondria, Mechanisms, and Molecular diagnostics

What is known about  Microbiomes, Metabolism, Mitochondria and Molecular diagnostics links any energy-dependent systems approach from -omics to Precision Medicine via the innate immune system. [30] All phenotypic expression starts with the energy-dependent creation of nucleic acids and the creation of G protein-coupled receptors. The receptors allow nutrients to enter cells. For example, see [31]

The energy-dependent creation of olfactory receptor genes links metabolism and mitochondrial function to stress-driven changes in neuroendocrine, metabolic, inflammatory, transcirptional responses and to differences in behavior. [32-33]

Expression of c-fos links gene expression in GnRH neurosecretory neurons from the first step to the final steps of cell type differentiation all vertebrates. [34-36]

Nutrient stress and social stress link changes in hydrogen-atom transfer in DNA base pairs in solution from pH and virus-driven energy theft to mutations and all pathology.[37]

GnRH secretion links nutrient energy-dependent RNA-directed DNA methylation to the stability of organized genomes RNA-mediated amino acid substitutions. [38]  See also: [39]

[30] Endolysosomal trafficking of viral G protein-coupled receptor functions in innate immunity and control of viral oncogenesis

[31] An Epigenetic Signature for Monoallelic Olfactory Receptor Expression

[32] Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress

[33] Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity

[34] Evolution of Constrained Gonadotropin-releasing Hormone Ligand Conformation and Receptor Selectivity

[35] Induction of FOS immunoreactivity in central accessory olfactory structures of the female rat following exposure to conspecific males,

[36] Stimulus-specific combinatorial functionality of neurona c-fos enhancers

[37]  Allosteric switch regulates protein–protein binding through collective motion

[38] Stress-induced gene expression and behavior are controlled by DNA methylation and methyl donor availability in the dentate gyrus,

[39] Direct evidence for sequence-dependent attraction between double-stranded DNA controlled by methylation

Conclusion:

Nutrient energy-dependent changes in base pairs link olfaction and c-fos expression from microRNAs to changes in the innate immune system via microRNA flanking sequences and energy-dependent DNA methylation that varies with stress.[40] In mammals, DNA methylation and microRNA activity link gene activation from olfaction to hormone-organized and hormone-activated behaviors via the secretion of hypothalamic gonadotropin releasing hormone (GnRH) and downstream effects on the hypothalamic-pituitary-gonadal (HPG) and HP-adrenal (HPA) axis. [41]

One base pair change and a single RNA-mediated amino acid substitution link the stability of viruses to the stability or the instability of metabolic networks and genetic networks in the organized genomes of all living genera. Energy-dependent RNA-mediated amino acid substitutions are inappropriately called mutations. [42-48] Mutations are linked from emergence to evolution by theorists who may not know anything about RNA-mediated biophysically constrained protein folding chemistry. Many theorists seem to know nothing about the conserved molecular mechanisms of healthy longevity and biodiversity in all living genera. See [49]

 [40] Rapid Down-Regulation of Glucocorticoid Gene Expression in the Dentate Gyrus after Acute Stress in vivo: Role of DNA Methylation and microRNA Activity

[41] Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders

[42] Molecular requirements for a pandemic influenza virus: An acid-stable hemagglutinin protein

[43] Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant

[44] The SNP rs1625579 in miR-137 gene and risk of schizophrenia in Chinese population: A meta-analysis

[45] COMT val158met polymorphism and molecular alterations in the human dorsolateral prefrontal cortex: Differences in controls and in schizophrenia

[46] Reduced protein synthesis in schizophrenia patient-derived olfactory cells

[47] Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity

[48] Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

[49] Essential role for a novel population of binucleated mammary epithelial cells in lactation

Chemistry

Energy is INFORMATION

Hydrogen atom transfer in DNA base pairs in solution

Photosynthesis

Nutritional epigenetics

base pair substitutions

microRNA flanking sequence

miRNA/mRNA balance

RNA/DNA Methylation

 RNA-mediated amino acid substitutions

Thermodynamic cycles of nutrient-dependent cell type differentiation

Quantum and Classical Physics

innate immune system

de novo creation of nucleic acids

microRNA (miRNA) biogenesis

alternative splicings / pre-mRNA

G protein-coupled receptor gene creation

Molecular Epigenetics

Olfactory receptor genes

 Food odors & Pheromones

 Feedback  loops

 Physiology of Reproduction

 RNA-mediated DNA repair

 Supercoiled DNA

 HHHealthy longevity

Excessive STRESS

 changes in pH

Virus-driven energy theft

ENTROPY

 Altered Brain development

 Altered Learning and memory

 Altered Life history transitions

 Altered Feedback loops

 Altered Reproduction & Aging

 Transgenerational epigenetic inheritance

 Virus-perturbed neural circuitry, odor hedonics, mood, memory, motivation, expressions of affect, cognitive behavioral state, and potentiating responses to other stimuli link energy theft from stress  to mutations and all pathology.

 

Youtube Narrative:

My name is James Kohl. I’m a medical laboratory scientist.

Physicists, chemists, and molecular biologists have linked energy-dependent changes in DNA base pairs from angstroms to ecosystems and healthy longevity in all living genera.

Energy is information. The innate immune system links the information from the epigenetic landscape to the de novo creation of genes and to the physical landscape of supercoiled DNA. Energy-dependent supercoiled DNA protects the organized genomes of all living genera from virus-driven energy theft.

Energy theft causes the accumulation of mutations that leads to all pathology.

In this presentation, I link ecological variation to energy-dependent RNA-mediated events and ecological adaptation. Chemical ecology links the energy-dependent events from nutrient-dependent microRNA flanking sequences to biophysically constrained protein folding chemistry. RNA-mediated protein folding chemistry links the conserved molecular mechanisms of cell type differentiation to all biodiversity.

Simply put, the sun’s biological energy links what organisms eat to cell type differentiation via the physiology of reproduction. Transgenerational epigenetic inheritance links single nucleotide polymorphisms and RNA-mediated amino acid substitutions, such as COMT Val158Met  and BDNF Val66Met to differences in phenotypes. Fixed amino acid substitutions exemplify differences in the morphological and behavioral phenotypes of all living genera.

The color-coded sections of the model include links to cited works that support the brief representations in the text. The center section of the poster attests to the fact that cause and effect is non-linear. Experience-driven changes link energy from physics and chemistry to molecular epigenetics via RNA-mediated protein folding.

That’s how experience links top-down causation from sunlight to molecular epigenetics and the morphological and behavioral phenotypes of all living genera across their lifespan. All life-sustaining interactions must be integrated during life history transitions and successful transitions are manifested as fixed amino acid substitutions.

The sections in yellow, green, and white link the anti-entropic quantised energy of the sun from the virucidal effects of ultraviolet light to healthy longevity. The citations attest to facts about energy-dependent hydrogen-atom transfer in DNA base pairs in solution. Biophysically constrained protein folding chemistry links hydrogen-atom transfer  from angstroms to ecosystems via pH in the context of cell type differentiation.

Facts about measured analytes in addition to pH link RNA-mediated amino acid substitutions to the energy-dependent physiology of reproduction. All facts about cell type differentiation link biophysically constrained protein folding chemistry to pH and protection from virus-driven entropy.

For contrast, everything in red links excessive nutrient stress and/or social stress from changes in pH and virus-driven energy theft to mutations and all pathology.  If everything in yellow, green, white, and red is not considered in the context of healthy longevity compared to virus-driven pathology, researchers and clinicians are left with theories.

In the context of genetics and genomics all theories are equally irrelevant compared to the facts that link angstroms to ecosystems. Virtually all theories ignore Schrodinger’s claims about the anti-entropic energy of sunlight. And most theories also ignore Dobzhansky’s claims about nutrient-dependent amino acid substitutions and biodiversity.

Facts link chemical ecology from quantum physics to olfaction and facts link the immune system and the sense of smell. The sense of smell is linked from symptoms of neurodegenerative diseases like Alzheimer’s to the hard problem of consciousness. The sense of smell also links the bull sperm microRNAome to microRNAs in human breast milk that are essential to brain development. Brain development occurs in the context of fixation of RNA-mediated amino acid substitutions that stabilize organized genomes.

In the age of Precision Medicine and problems like energy theft by the Zika virus, genomics and genetics must be linked by facts about cell type differentiation. What is known about  Microbiomes, Metabolism, Mitochondria and Molecular diagnostics links this energy-dependent systems approach from the innate immune system to Precision Medicine.  All phenotypic expression starts with the energy-dependent creation of nucleic acids and the creation of G protein-coupled receptors. The receptors allow nutrients to enter cells.

Receptor-mediated gene expression links c-fos in the gonadotropin releasing hormone neurosecretory neurons of all mammals from the first step to the final step of cell type differentiation in all vertebrates. That fact has been known for more than two decades.

MicroRNA flanking sequences link nutrient energy-dependent RNA-directed DNA methylation and histone acetylation to the stability of organized genomes via RNA-mediated amino acid substitutions in all genera. That fact has been known for more than a year.

Conclusion:

Nutrient energy-dependent changes link olfaction and c-fos expression from microRNAs to changes in the innate immune system via microRNA flanking sequences and energy-dependent DNA methylation that varies with stress. In mammals, DNA methylation and microRNA activity link gene activation from olfaction to hormone-organized and hormone-activated behaviors via the secretion of hypothalamic GnRH and downstream effects on the HPG and HPA axis.

One base pair change and a single RNA-mediated amino acid substitution link the stability of viruses to the stability of metabolic networks and genetic networks in the organized genomes of all living genera. Unfortunately, energy-dependent RNA-mediated amino acid substitutions are frequently called beneficial mutations by theorists.

Definitions of mutations and assumptions about what mutations do has biased biodiversity research and patient outcomes since de Vries defined “mutation” in 1904.

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