RNA-mediated DNA modifications

By: James V. Kohl | Published on: March 1, 2016

A new way to discover DNA modifications


Using their approach, which combines bioanalytical chemistry, comparative genomics, and a special type of DNA sequencing, the team has discovered a DNA modification that helps bacteria to protect their genomes from viral infection.

My comment: There is one way to link nutrient-dependent microRNA flanking sequences from adhesion proteins to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. It starts with energy-dependent changes in hydrogen-atom transfer in DNA base pairs and links them to the nutrient-dependent RNA-mediated amino acid substitutions that differentiate all cell types of all individuals of all living genera.
The amino acid substitutions link RNA-mediated DNA repair from the de novo creation of olfactory receptor genes to the physiology of reproduction. Viruses steal the energy required to support the physiology of reproduction. The theft of energy by viruses links mutations to loss of function in the context of nutrient stress or social stress, which is linked to all pathology.
If their approach starts with bioanalytical chemistry, they will not link quantum physics to comparative genomics.  Until they start from what is known about quantum physics, their link to protection of organized genomes from viral infection will be incomplete.
I’ve already linked angstroms to ecosystems and it is time for them to catch up.  It is also time for everyone to stop reporting that they have found a new way to discover how hydrogen-atom transfer in DNA base pairs in solution is linked from the sun’s biological energy to all DNA modifications via RNA-mediated events linked to all cell type differentiation in all individuals of all living genera.
See also: Pre-transition effects mediate forces of assembly between transmembrane proteins


The orderphobic effect generates forces of assembly and facilitates protein mobility

My comment: When I read this I thought it suggested the effect generates the forces of the orderphobic effect, a circular argument common among theoretical physicists and evolutionary theorists. The authors clarified the fact that top-down causation is more complicated then a claim that magically links it to protein assembly and mobility.

Their clarification:

Biological membranes and transmembrane proteins are far more complicated than the models considered in this paper. Part of the complexity is associated with multiple components, which allow for more than one order–disorder transition. For example, with a membrane composed of three components, coexistence can be established between liquid-ordered and liquid-disordered phases [47], and both of these phases exist in bio-membranes [6, 7, 8]. The fact that liquid-ordered and liquid-disordered phases can coexist with finite line tension [47] implies the existence of a first-order transition between them [48] and thus the relevance of the orderphobic effect.

My comment: First-order transition in biological membranes links the biological energy of the sun and speed of light on contact with water to the de novo creation of nucleic acids. The creation of nucleic acids links ribonucleic acid (RNA) from biophysically constrained protein folding chemistry to the transmembrane proteins and receptor-mediated cell type differentiation. For example, the de novo creation of G protein-coupled receptors (GPCRs) links chemotaxis and phototaxis to RNA-mediated cell type differentiation and the energy-dependent stability of organized genomes in all living genera.

That fact may be apparent to anyone who has performed blood gas analysis in the lab. Measures of oxygen, carbon dioxide, and pH are carefully calibrated and controls are frequently run to ensure that the results are accurately reported. But, without a model of biologically-based cause and effect that links the results to a patient outcome, even medical laboratory scientists may not understand how their results link physics to chemistry and the conserved molecular mechanisms of healthy longevity.

For an example of what must be included as the basis for the model, see: The architecture of the human RNA-binding protein regulatory network


We suggest that RBP chains use the modulation of RBP targets as a “connector” to different processes. Like a piping system bringing the “fluid” (regulation) to the various distribution centers (the RBPs) which then open their “valve” (regulate their targets) to influence the functions of interest and pump the “fluid” to the next level (next RBP of the chain). Non-chain interactions could then act as chain modulators (e.g. by stopping transmission halfway through, or further enhancing its flow). Under this model, RBP-RBP interactions constitute a post-transcriptional backbone, with RBPs acting as “split-flow” pumps to drive regulation and tune protein abundances.

My comment: The author’s attest to the systems complexity in terms that make sense to engineers and non-scientists: connectors; fluid regulation; valves; and split flow pumps. But what is the energy source for all the interactions? They also mention the evolution of proteins, as if they were trying to explain the mechanisms of nutrient-dependent RNA-mediated cell type differentiation to a neo-Darwinian theorist.

They stopped short and failed to mention the evolution of proteins in the context of evolutionary rates of sequence divergence. That suggests to me their accurate representation of how biophysically constrained nutrient-dependent RNA-mediated protein folding chemistry links amino acid substitutions to cell type differentiation in all living genera via the physiology of reproduction, lack only one thing. What is the power source that runs the molecular mechanisms they describe? How is hydrogen-atom transfer in DNA base pairs in solution linked to supercoiled DNA and protection against virus-driven entropy?

See also: Differential Phosphorylation Provides a Switch to Control How α-Arrestin Rod1 Down-Regulates Mating Pheromone Response in Saccharomyces cerevisiae

My comment: If others cannot get from the nutrient-dependent pheromone-controlled physiology of reproduction in yeasts to brain development in humans via the conserved molecular mechanisms of biologically-based cause and effect we detailed in 1996, they may waste another decade or two on research that cannot be placed into the context of any model.

See also: How the Brain Is Computing the Mind A Conversation With Ed Boyden [2.12.16]

Excerpt 1)

One of my dreams is you could take a bacterium or a virus and expand it until you can take a picture on a cell phone. Imagine how that could help with diagnostics, right? You could find out what infection somebody has just by making it bigger, take a picture and you’re done.

My comment: In 2006, Greg Bear incorporated that dream into the plot of his science fiction novel, “Quantico

Excerpt 2)

…we put molecules that are light sensitive into neurons and then we can make them activatable or silence-able with pulses of light.

Our groups have sent these molecules out to literally thousands of basic as well as clinically interested neuroscientists, and people are studying very basic science questions like how is a smell represented in the brain? But they’re also trying to answer clinically relevant questions…

My comment: In 1980, Lewis Thomas suggested that the answer to the question of how smells are represented in the brain is the most clinically relevant question of all.


I should think we might fairly gauge the future of biological science, centuries ahead by estimating the time it will take to reach a complete comprehensive understanding of odor. It may not seem a profound enough problem to dominate all the life sciences, but it contains, piece by piece, all the mysteries (p. 732).

See also: The Dlx5 and Foxg1 transcription factors, linked via miRNA-9 and -200, are required for the development of the olfactory and GnRH system


…studies specifically addressing the expression and function of miR in GnRH neurons are needed to dissect their role in the genesis, migration and maturation of this specific cell type. At present, a systematic study to identify specific miRs relevant for early GnRH neuron development, in vitro or in vivo, has not been reported, as yet. Thus, our results provide the first evidence of the participation of miR-9 and miR-200-class in these early events. We further link two transcription factors with the action of these miRs.

My comment: Our 1996 Hormones and Behavior review of RNA-mediated events link olfaction from pre-mRNAs, which are now called microRNAs,  e.g., miRNA-9 and miRNA-200, to epigenetically-effected cell type differentiation in species from microbes to humans via the conserved molecular mechanisms that link food odors and pheromones to the physiology of reproduction.  More studies will only continue to support the model from the molecular epigenetics section, which has already been supported in any published works by serious scientists during the past 20 years.

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