Modelling life scientifically: RNA-mediated events
By: James V. Kohl | Published on: June 10, 2016
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Experiment: “An attempt to arrive at an accurate result.” — James V. Kohl (3/27/16) EFBC fellowship class response to Dr. Tom Jordan who asked me to define “experiment”
An experiment is a procedure carried out to verify, refute, or validate a hypothesis. Experiments provide insight into cause-and-effect by demonstrating what outcome occurs when a particular factor is manipulated. Experiments vary greatly in goal and scale, but always rely on repeatable procedure and logical analysis of the results.
My comment: Experimental evidence of biologically-based cause and effect can be compared in the context of theory.
Theory is a contemplative and rational type of abstract or generalizing thinking, or the results of such thinking. Depending on the context, the results might for example include generalized explanations of how nature works.
My comment:ย Theories about evolution have no explanatory power. The theories cannot be placed into the context of experimental evidence, which is used to model the understanding of life.
A scientific model seeks to represent empirical objects, phenomena, and physical processes in a logical and objective way. All models are in simulacra, that is, simplified reflections of reality that, despite being approximations, can be extremely useful.[4] Building and disputing models is fundamental to the scientific enterprise. Complete and true representation may be impossible, but scientific debate often concerns which is the better model…
My comment: Which do you think has more explanatory power, the ridiculous theory in 1), or the model in 2)?
1) “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world.” — Mutation-Driven Evolution
2) “…the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific โfitโ. — Nutrient-dependent/pheromone-controlled adaptive evolution: a model
My comment: The model can be placed into the context of everything currently known to serious scientists about the biophysically constrained chemistry of RNA-mediated protein folding.
“We previously showed that worms inherited small RNAs following the starvation and viral infections of their parents. These small RNAs helped prepare their offspring for similar hardships,” Dr. Rechavi said. “We also identified a mechanism that amplified heritable small RNAs across generations, so the response was not diluted. We found that enzymes called RdRPs are required for re-creating new small RNAs to keep the response going in subsequent generations.
A recent experiment4 suggests that room-temperature superconductivity is reachable in other hydrogen-rich compounds. Our results show that in such hydrogen-rich materials with prospects for high-Tc superconductivity, the quantum motion of the proton induces non-trivial effects that strongly affect the thermodynamical stability, the hydrogen chemical bonding and the electronโphonon coupling strength.
…quantum nature affects structural and physical properties of many hydrogen compounds.
My comment: On 3/13/16, I discussed virus-driven energy theft in the context of hydrogen-atom transfer in DNA base pairs in solution and pathology with a college student who is familiar with my model. He intuitively realized that the energy theft must occur at the level of quantum mechanics.
That suggests these researchers, or others will someday integrate what is known about molecular epigenetics and place everything from quantum physics and chemistry into the context of nutrient-dependent RNA-mediated amino acid substitutions that link supercoiled DNA to biologically-based cause and effect via the physiology of reproduction in the context of the innate immune system and links from olfaction to the structure and function of the mammalian brain.
Physicists now seem to realize that epigenetically-effected RNA-mediated cell type differentiation is biophysically constrained by ecological variation. Jeremy England’s group is one of the first to start with an energy source at the molecular level. SARCASM ALERT: Next, they may prove that food is the underlying source of what is known about nutritional epigenetics and RNA-mediated protein folding chemistry. Physicists prove energy input predicts molecular behavior Excerpt 1)
This is a general proof that shows that how much energy you feed the system is related in a quantitative way to how reliable you’ve made it,” England says. “Having this constraint immediately gives you intuition, and a sort of road-ready yardstick to hold up to whatever it is you’re trying to design, to see if it’s feasible, and to direct it toward things that are feasible.”
Excerpt 2)
“We have in mind trying to make some sense of molecular systems,” Gingrich says. “What this proof tells us is, even without observing every single feature, by measuring the amount of energy lost from the system to the environment, it teaches us and limits the set of possibilities of what could be going on with the microscopic motions.”
Excerpt 3)
“One of the things that’s confusing about life is, it happens on a microscopic scale where there are a lot of processes that look pretty random,” Gingrich says. “We view this proof as a signpost: Here is one thing that at least must be true, even in those extreme, far-from-equilibrium situations where life is operating.”
My comment: It’s challenging for serious scientists to see claims like this and not laugh about how long it has taken theorists to recognize that an energy source must link atoms to ecosystems in all living genera. All serious scientists know that the link from atoms to ecosystems has been placed into the context of the nutrient-dependent RNA-mediated immune system. See:ย Regulatory evolution of innate immunity through co-option of endogenous retroviruses Excerpt:
It would be ironic if viral molecular adaptations had been evolutionarily recycled to fuel innovation and turnover of the host immune repertoire.
My comment: It would not be ironic. It would again prove that mutations can only be linked to pathology. It would prove that ecological variation must be linked from physics and chemistry to the conserved molecular mechanisms of cell type differentiation by the feedback loops that link odors and pheromones to reproduction in species from microbes to man. See:Feedback loops link odor and pheromone signaling with reproduction Excerpt:
Interacting physical systems not only exchange energy, but also exchange information as they learn about and influence each other. Harnessing this information how to do useful tasks is vital in a variety of disciplines: engineers exploit information through feedback to control a system’s dynamical evolution [1, 2], biological organisms need to sense their environment in order to adapt [3], and physicists have been fascinated by the conceptual problems posed by Maxwell’s demon for over 100 years [4, 5].
“Sci-fi author Greg Bear came very close in his marvelous 1999 and 2003 novels Darwinโs Radio and Darwinโs Children. He imagines that a latent retrovirus awakened in the genomes of pregnant women in 1999 shuffled the genomes of a new generation in ways that created cells with 52 chromosomes instead of 46, thereby instantly establishing a group that can successfully mate only among themselves. Youโll have to read the books to learn how and why the โvirus childrenโ are superior. Forced into camps by the fearful majority, they establish their own culture, further separating the two types of people, a little bit reminiscent of a presidential election in the US. Bearโs alternate reality is a compelling depiction of reproductive isolation leading, presumably, to speciation, with an initial chromosomal upheaval as the impetus.
I spoke to Bear back in 2004, again for The Scientist (a mechanism for the rapid extinction of a dedicated freelance writer is a change in editor-in-chief). Greg Bear is a self-taught scientist with a soaring imagination. Said he, โMy secrets are few. I love biology. I have been researching it in constant reading since the early 1980s. I saw very clearly that DNA must be computational, a self-organizing, self-repairing system. In the early 90s, it became clear to me that modern evolutionary theory was incomplete. I set out to find all the out-of-the-way papers that I could to prove that nature was a network, from top to bottom.โ The Darwin series arose from those thoughts… “
Wilson says it is time for the popular paradigm of โkin selectionโ to be replaced by group selection when it comes to the evolution of cooperation. What boggles the mind is that kin selection was earlier welcomed as a breakthrough in evolutionary theory just because it was seen as replacing the then prevailing group selectionist โgood for the speciesโ thinking.. What is going on?
My comment: Virus-driven energy theft has been linked from mutations to loss of function via genes that are eliminated after first becoming pseudogenes. Simply put, all serious scientists have learned that there is no such thing as a beneficial mutation. That’s what’s going on. Pseudoscientists refuse to believe that facts about cell type differentiation.ย See for comparison:ย Cori Bargmann: Genes, the Brain and Behavior Excerpt:
By focusing on the genes for a family of proteins found in many organisms, the G protein-coupled receptors, Bargmann illustrates that mutations in a single gene can cause significant behavioral changes in organisms as diverse as nematodes, dogs and humans. In Part 2, Bargmann presents work from her own lab in which the olfactory system in C. elegans was used to dissect the role of genes on behavior. She shows us how it was possible to map the neuronal circuits that modulate worm behavior in response to different odors.
Building on her olfaction work, Bargmann has also studied the neural basis of social behavior, which in worms is strongly regulated by chemical cues. In one set of papers, for example, she identified a single neuron that integrates information from multiple chemical cues including food, oxygen and pheromones, to control the expression of social behavior.
My comment: On March 30, 2016 at 4.00 pm,ย Dr. Bargmann at 4.00 pm will deliver a lecture entitled โGenes, neurons, circuits and behavior: an integrated approach in a compact brainโ
It is hard for me to imagine anything that she might present that has not already been linked from RNA-mediated events to brain development and behavior.
Work from our and other laboratories indicates that spermatozoa act as vectors not only of their own genome, but also of foreign genetic information, based on their spontaneous ability to take up exogenous DNA and RNA molecules that are then delivered to oocytes at fertilization with the ensuing generation of phenotypically modified animals [35] – [37]. In cases in which this has been thoroughly investigated, the sperm-delivered sequences have been seen to remain extrachromosomal and to be sexually transmitted to the next generation in a non-Mendelian fashion [38]. The modes of genetic information delivery in this process are closely reminiscent of those operating in RNA-mediated paramutation inheritance, whereby RNA is the determinant of inheritable epigenetic variations [16], [17]. In conclusion, this work reveals that a flow of information can be transferred from the soma to the germline, escaping the principle of the Weismann barrier[39] which postulates that somatically acquired genetic variations cannot be transferred to the germline.
My comment: This ability is not spontaneous and their conclusion was reported on July 3, 2014. The delayed reporting can be attributed to the fact that RNA-mediated events link physics to chemistry and the conserved molecular mechanisms of cell type differentiation in all living genera via transgenerational epigenetic non-Mendelian inheritance. That fact links what Darwin knew about Mendel’s works to his claims about “conditions of life” and the need to put those conditions before any claims about natural selection. (Darwin knew nothing about Mendel’s works, but he obviously suspected that evolution via natural selection did not automagically happen outside the context of his “conditions of life.” Perhaps the real reason he waited so long to publish was that he could predict what pseudoscientists would do to his theory and make ridiculous claims about the fossil record was somehow linked to the evolution of new species from older extinct species.
…exosomes are the carriers of a flow of information from somatic cells to gametes,” and that their “results indicate that somatic RNA is transferred to sperm cells, which can therefore act as the final recipients of somatic cell-derived information.
…if foods that we eat are also capable of acting as vectors of gene-regulatory information, truly the old reductionist, mechanistic, unilinear models of genetics must be abandoned in favor of a view that accounts for the vital importance of all our decisions, nutritional factors, environmental exposures, etc., in determining the course, not only of our bodily health, but the health of countless future generations as well.
How many more times can we expect to see the same report raise questions about nutrient-dependent pheromone-controlled RNA-mediated cell type differentiation that have been answered in all literature published by serious scientists since 1996? See: From Fertilization to Adult Sexual Behavior
Excerpt:ย
Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.
My comment: How else might sex differences or somatic differences arise? All cell type differences are nutrient-dependent and all cell type differentiation is RNA-mediated. If that fact were not true, teleophobes would have long ago offered an alternative model of how cell type differentiation occurs in the context of mutations and evolution. Compared to the claims of serious scientists who have linked atoms to ecosystems the claims of theorists are simple-minded and foolish.
In the D279R KIF5B-ฮฒ-R262H MT mutant pairs, neither the motility nor the ATPase was rescued (Table 1). This result is not surprising considering the high histidine activity in molecular interactions30. Because histidine is capable of interacting with various amino acids, the mutation R262H might have modulated the MTs by hydrogen bonding(s), which cannot be compensated by D279R KIF5B11.
My comment: They link the flow of energy as information from physics to a mutation that disrupts the flow and claim that an amino acid substitution restores the information flow. But they claim the amino acid substitution is a mutation. This is what Taylor et al., (2015) did with two amino acid substitutions in Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system. Excerpt:
After 96 hours of incubation of AR2 and Pf0-2x at room temperature on SMM, two breakout mutations were visible, conferring first slow (AR2S and Pf0-2xS) and then fast (AR2F and Pf0-2xF) spreading over the agar surface (Fig. 1A). The AR2F strain produces flagella, but we could not detect flagella in electron microscopy samples for AR2S (Fig. 1B). Genome resequencing revealed a single-nucleotide point mutation in ntrB in strain AR2S, causing an amino acid substitution within the PAS domain of the histidine kinase sensor NtrB [Thr97โPro97 (T97P)] (13). The fast-spreading strain AR2F had acquired an additional point mutation in the ฯ54-dependent EBP gene ntrC, which alters an amino acid (R442C) within the DNA binding domain (Table 1 and table S2).
(A) Diagram of the NBDwt and NBDmut peptides. The W amino acids in the NBDwt peptide were substituted by A in the NBDmut (highlighted in red).
My comment: They are treating mutations linked to cancer with amino acid substitutions. There must be a reason for accurately reporting their claims in the context of what is known about the nutrient-dependent stability of organized genomes. If they did not know how to link atoms to ecosystems in all living genera via metabolic and genetic networks, they could not be considered serious scientists by their peers. All serious scientists know the difference between a mutation and an amino acid substitution. Only teleophobes and pseudoscientists are confused. Serious scientists link top-down causation to cell type differentiation in the context of hydrogen-atom transfer in DNA base pairs. My comment: They link a mutation/deletion to the need for DNA repair. That is what serious scientists have been doing for several decades. They start with E. Coli and link the conserved molecular mechanisms to the stability of all organized genomes in all living genera See, for example: CryoEM and computer simulations reveal a novel kinase conformational switch in bacterial chemotaxis signaling Excerpt:
…improving the resolution of our cryoET data to better than 8ร using the novel lipid-monolayer system described above would allow generation of an atomic homology model of the E. coli chemosensory array…
My comment: Improving the resolution is less important that finding a teleophobic theorist who will publicly admit that no neo-Darwinian theorist, since Dobzhansky (1973) has ever understood anything about how nutrient-dependent pheromone-controlled cell type differentiation occurs in the context of hydrogen-atom transfer in DNA base pairs linked to the amino acid substitutions that determine RNA-mediated cell type differences in all living genera.
The facts about hydrogen-atom transfer in DNA base pairs attest to the misrepresentations made in the context of ridiculous theories about mutations and evolution. For example, the Red Queen hypothesis arose in the context of claims that “Evolutionary change may be required to stay in the same place. Cessation of change may result in extinction.”
But ecological variation must lead to ecological adaptation via RNA-mediated amino acid substitutions, not by mutations and evolution. Simply put, organisms that cannot find food and reproduce become extinct, they do not change and become another species. Summary: None of the factual representations of biologically-based cause and effect seem to be integrated in the latest report from Science, which could have a huge impact on the future of synthetic biology. The team created a new species of microorganism with a minimal genome. The bacterial cell has 473 synthetic genes. The function of 31.5% of these genes remains unknown, and very few reports make the obvious connection from the unknown function of 149 genes to the function of the innate immune system. See: Synthetic microbe lives with fewer than 500 genes (Science news) Craig Venterโs Synthetic Genome 3.0 Evokes Classic Experiments (DNA Science Blog) โMinimalโ cell raises stakes in race to harness synthetic life (Nature News) The Mysterious Thing About a Marvelous New Synthetic Cell (the Atlantic) After 20 Year Quest, Biologists Create Synthetic Bacteria With No Extra Genes (Forbes)
It is a video review of what neo-Darwinists still believed about biophysically constrained energy-dependent RNA-mediated events only 7 years ago (April 2009)
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