Alternative splicing of pre-mRNA

Energy-dependent de novo creation and neurogenesis (2)

See also: Energy-dependent de novo creation and neurogenesis
12/7/16 Atlas of the RNA universe takes shape

MicroRNA are very mysterious. They are really relics of the RNA world—pieces of RNA that are highly reactive, very small and which pair and bind other RNA and facilitate catalytic reactions,” Mangone says. “We don’t know much about them—where they come from or how they regulate gene expression, but they are very misregulated in many diseases.

See also: Nutrient-dependent/pheromone-controlled adaptive evolution: a model Published 14 Jun 2013

…the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution. The role of the microRNA/messenger RNA balance (Breen, Kemena, Vlasov, Notredame, & Kondrashov, 2012; Duvarci, Nader, & LeDoux, 2008; Griggs et al., 2013; Monahan & Lomvardas, 2012) in adaptive evolution will certainly be discussed in published works that will follow.

My comment: Only if you lived among wolves or among theorists for the past 10 years would you not know that more than 55,000 indexed publications link energy-dependent changes in the microRNA/messenger RNA balance to healthy longevity. For comparison, all serious scientists also know that virus-driven energy theft links viral microRNAs from mutations to all pathology.
You need only search for “RNA mediated” to find information on how cellular and viral microRNAs are linked from energy-dependent changes to RNA-mediated amino acid substitutions and biophysically constrained protein folding chemistry. For example, this is all it takes to recognize the amount of pseudoscience that is packaged in claims that we don’t know much about microRNAs.
See also: Published to Figshare 10 April 2014

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches.

See also: MicroRNAs: the future of genomic science?

The ubiquity of miRNA occurrence is reflected in the current literature, which reports a wide range of potential biomarker applications for this highly conserved molecule.

My comment: MicroRNAs are biomarkers that clearly link energy-dependent biophysically constrained changes in base pairs from RNA-mediated amino acid substitutions to cell type differentiation in all living genera. The energy-dependent links from the innate immune system to the physiology of reproduction also link all metabolic networks to all genetic networks in species from microbes to humans.
See for comparison: A single splice site mutation in human-specific ARHGAP11B causes basal progenitor amplification

…we hypothesize that the novel, human-specific C-terminal sequence of modern ARHGAP11B has a key role in the mechanism by which this protein promotes BP amplification. In this regard, the present data show that this sequence is due to a single C→G base substitution, which creates a novel splice donor site that results in the replacement of the ancestral C-terminal sequence of the ARHGAP11B GAP domain. The present data also demonstrate that this single C→G base substitution underlies the ARHGAP11B-mediated BP amplification implicated in neocortex expansion.

Reported as: Small Mutation Contributed to Evolution of Bigger Human Brains

A single base change in a human gene likely played an important role in evolutionary expansion of the human brain, researchers say.

My comment: They claim that a single cytosine to guanine substitution created a novel splice site. They failed to mention that base pair (BP) amplification is nutrient energy-dependent. They also failed to mention that the de novo creation of a novel splice donor site must be linked from the energy-dependent fixation of an RNA-mediated amino acid substitution to the physical landscape of supercoiled DNA via the physiology of reproduction.

Svante Paabo is one of the co-authors who reported this:

Hence, it is not the ARHGAP11 partial gene duplication event ~5 million years ago, as such, that impacted human neocortex evolution. Presumably, ARHGAP11A and ancestral ARHGAP11B coexisted as functionally similar proteins for some time after the gene duplication event. The ability of ARHGAP11B to amplify BPs likely arose more recently from a change that is tiny on a genomic scale but substantial in its functional and evolutionary consequences.

My comment: No experimental evidence of biologically-based cause and effect suggests that any partial gene duplication event ~5 million years ago could have linked a mutation and the altered de novo creation of genes that Svante Paabo (and co-authors) placed into the context  of biophysically constrained biodiversity in:

Natural Selection on the Olfactory Receptor Gene Family in Humans and Chimpanzees

My comment: Natural selection for energy-dependent codon optimality is the only way to link the de novo creation of genes from autophagy to RNA-mediated amino acid substitutions and nutrient-dependent polycombic ecological adaptation.
See: From Fertilization to Adult Sexual Behavior

Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). 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.

See also: PTBP1 and PTBP2 Serve Both Specific and Redundant Functions in Neuronal Pre-mRNA Splicing

…the two paralogs displayed similar RNA binding across the transcriptome, indicating that their differential targeting does not derive from their RNA interactions, but from possible different cofactor interactions.

My comment: The cofactors are nutrient energy-dependent microRNAs, which are linked to healthy longevity and all biodiversity and viral microRNAs, which are linked from mutations to all pathology.
See also: Viral and cellular messenger RNA targets of viral microRNAs

…viral miRNAs may be particularly important for regulating the transition from latent to lytic replication and for attenuating potentially inhibitory host antiviral immune responses.

See also: Nothing in Biology Makes Any Sense Except in the Light of Evolution

…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla (p. 127).”

See also: Light- and Carbon-Signaling Pathways. Modeling Circuits of Interactions

…carbon either attenuated or potentiated light repression of ASN1 in light-grown plants. These studies indicate the interaction of carbon with blue, red, and far-red-light signaling and set the stage for further investigation into modeling this complex web of interacting pathways using systems biology approaches.

My comment: When did theorists decide to take the light as information and energy out of systems biology and ecological adaptations? Who decided to replace the anti-entropic virucidal energy of light with mutations and evolution?

Alternative splicing of pre-mRNA

DNA repair via junk DNA (2)

See also: DNA repair via junk DNA (1)

Recently Evolved Genes Identified From Drosophila yakuba and D. erecta Accessory Gland Expressed Sequence Tags (2006)

Reported in Singer (2015) as:

In 2006, Begun found some of the first evidence that genes could indeed pop into existence from noncoding DNA.

Singer’s claim that genes automagically pop into existence is consistent with Masatoshi Nei’s conclusion in: Mutation-Driven Evolution

…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements. (p. 199)

See also: Viral Proteins Originated De Novo by Overprinting Can Be Identified by Codon Usage: Application to the “Gene Nursery” of Deltaretroviruses

Diethard Tautz suggested that this representation was a “…fact that is often used as additional evidence for the power of de novo evolution.” Apparently, Tautz believes that the magic of gene evolution in viruses can be linked to his claims about the magic of evolution in Evolution: Dynamics of De Novo Gene Emergence

See my August 20, 2015 comment on Singer (2015):

Re: Viruses are certainly not ignored, but can be excluded in most cases.

In a recent interview, Eugene Koonin made the opposite claim. See:

Excerpt: “The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis…”

Begun is the senior author of: Origin and Spread of de Novo Genes in Drosophila melanogaster Populations (2014)


…important details of such processes remain obscure and much additional work is required to clarify the dynamics, biochemical and genetic properties, and phenotypic effects of young de novo genes and the processes underlying gene loss in natural populations.

The works by Begun, Tautz, and others who have claimed that the de novo origin of genes that pop into existence can lead to evolution were reported by Carl Zimmer in The Continuing Evolution of Genes


As genes duplicate over millions of years, they can grow into so-called gene families, each containing hundreds of similar genes.

One family, for example, is essential for our sense of smell. These genes encode 390 different kinds of proteins produced in our noses, called olfactory receptors. Each olfactory receptor has a slightly different structure, allowing it to capture a different set of molecules.

My comment: Gene duplication is energy-dependent. The energy-dependent de novo creation of olfactory receptor genes links hydrogen-atom transfer in DNA base pairs in solution from changes in the microRNA/messenger RNA balance to alternative RNA splicings that link natural selection for energy-dependent codon usage from the innate immune system to supercoiled DNA via the physiology of reproduction in all living genera.

Why have some science journalists continued to place the pseudoscientific nonsense touted by theorists into the context of emergence and evolution?  Do they ever wonder how gene duplication occurs in the absence of nutrient-energy dependent changes in organized genomes, or where the organized genomes came from?

See also: Combinatorial epigenetics, “junk DNA”, and the evolution of complex organisms (2007)

Inheritable epigenetic changes (“epimutations”) with effects at a distance would then perdure over the number of generations required for “assimilation” of the several regulatory novelties through the occurrence and selection, gene by gene, of specific classical mutations. These mutations would have effects similar to the epigenetic effects, yet would provide stability and penetrance. The described epigenetic/genetic partnership may well at times have opened the way toward certain complex new functions. Thus, the presence of “junk DNA”, through co-determining the (higher or lower) order and the variants of chromatin structure with regulatory effects at a distance, might make an important contribution to the evolution of complex organisms.

See for comparison:  ENCODE Project Writes Eulogy for Junk DNA September 7, 2012.
See also The Case for Junk DNA (2014) reported by Carl Zimmer

Even if ninety percent of the genome does prove to be junk, that doesn’t mean the junk hasn’t played a role in our evolution. As I wrote last week in the New York Times, it’s from these non-coding regions that many new protein-coding genes evolve. What’s more, much of our genome is made up of viruses, and every now and then evolution has, in effect, harnessed those viral genes to carry out a job for our own bodies. The junk is a part of us, and it, too, helps to make us what we are.

*I mean functional in terms of its sequence. The DNA might still do something important structurally–helping the molecule bend in a particular way, for example.

[Update: Fixed caption. Tweaked the last paragraph to clarify that it’s not a case of teleology.]

Look again at Singer (2015) A Surprise Source of Life’s Code: Emerging data suggests the seemingly impossible — that mysterious new genes arise from “junk” DNA (2015)

“How does novel gene become functional? How does it get incorporated into actual cellular processes?” McLysaght said. “To me, that’s the most important question at the moment.”

My comment: Claims that genes pop into existence do not address how the genes are created or how they are incorporated into actual cellular processes. There is only one way for incorporation into cellular processes to occur. The innate immune system must link RNA-mediated cell type differentiation from amino acid substitutions to supercoiled DNA via the nutrient energy-dependent creation of G protein-coupled receptors that link receptor-mediated behavior from natural selection for codon optimality to supercoiled DNA. The supercoiled DNA is the link from non-coding DNA to the epigenetically-effected organized genomes of all living genera.
See for instance:
Junk DNA: A Journey Through the Dark Matter of the Genome (2015) reviewed by Casey Luskin in New Book on “Junk DNA” Surveys the Functions of Non-Coding DNA

The bits of gobbledygook between the parts of a gene that code for amino acids were originally considered to be nothing but nonsense or rubbish. They were referred to as junk or garbage DNA, and pretty much dismissed as irrelevant. … But we now know that they can have a very big impact. (pp. 17-18)

The impact of the amino acids links everything known about molecular epigenetics to RNA-mediated DNA repair. The epigenetically-effected RNA-mediated amino acid substitutions in organized genomes must link the initiation of DNA repair to the maintenance of organized genomes throughout the life history transitions of all living genera. Simply put, the energy-dependent RNA-mediated amino acid substitutions are linked to healthy longevity.
Codon optimality controls differential mRNA translation during amino acid starvation

Our data reveal a previously unappreciated mechanism underlying cellular adaptation to amino acid shortage at the level of mRNA translation.

A chemical-inducible CRISPR-Cas9 system for rapid control of genome editing

For spatial control, one may apply photocaged tamoxifen or 4-HT and use ultraviolet light to target a subset of cells within a mixed population34. Hence, our ERT2-based iCas technology expands the toolkit for precise genome engineering in mammalian cells.

ADAR-Mediated RNA Editing Predicts Progression and Prognosis of Gastric Cancer

Gastric cancer (GC) is the third leading cause of global cancer mortality. Adenosine-to-inosine RNA editing is a recently described novel epigenetic mechanism involving sequence alterations at the RNA but not DNA level, primarily mediated by ADAR (adenosine deaminase that act on RNA) enzymes. Emerging evidence suggests a role for RNA editing and ADARs in cancer, however, the relationship between RNA editing and GC development and progression remains unknown.

My comment: ADAR is Adenosine-to-inosine RNA editing. They fooled you, didn’t they? If you did not think it was something new, you probably are a serious scientist, or more biologically informed than any theorist.
L1-associated genomic regions are deleted in somatic cells of the healthy human brain
My comment: They cite Needleman, S.B. & Wunsch, C.D. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J. Mol. Biol. 48, 443–453 (1970).
A Fear of Pheromones (1971)

What on earth would we be doing with such things? With the richness of speech, and all our new devices for communication, why would we want to release odors into the air to convey information about anything?

On Smell (1980)

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).

— Lewis Thomas as cited in The Scent of Eros: Mysteries of Odor in Human Sexuality (1995/2002)



Stress-linked population-level history dependence

The Science of President Trump

My comment: Trump is not a president. He may be the Republican front-runner. In any case, attempts to portray him as a president in the context of “science” must be viewed in the context of pseudoscientific nonsense and media misrepresentations. Many political views on science are unrealistic because they are based on the pseudoscientific nonsense touted by neo-Darwinian theorists. If someone thinks that nutrient-dependent pheromone-controlled multicellularity automagically evolved, their thought processes have probably already been subjected to stress-linked pathology caused by the viruses that prevent healthy longevity. Stress-linked pathology links cell type differentiation from single-celled organisms to other primates and to humans via the conserved molecular mechanisms of biologically-based cause and effect. See for example:

Response of single bacterial cells to stress gives rise to complex history dependence at the population level


Investigating how the behavior of single cells scales up to history dependence at the population level is an important goal. Many microorganisms live in dynamic environments where the quality and quantity of nutrients and biological, physical, and chemical stressors change continuously. Therefore understanding how microorganisms operate in such dynamic environments is a fundamental question. In addition, such understanding also has potentially relevant applications, for example in the context of pathogens that are exposed to fluctuating concentrations of antibiotics during treatment or microorganisms in technical systems that are exposed to dynamic operating conditions. Single-cell measurements help to achieve a deeper understanding of history-dependent processes in microbial populations.

My comment: Investigating the behavior of single cells leads to wrong conclusions when the energy required for the behavior is not considered. Neo-Darwinists typically do not consider the energy-dependent hydrogen-atom transfer in DNA base pairs in solution that is required to place the continuously changing “…quality and quantity of nutrients and biological, physical, and chemical stressors…” into the perspective of supercoiled DNA, which links metabolic networks and genetic networks from atoms to ecosystems in all living genera. For example, supercoiled DNA protects our organized genomes from virus-driven energy theft that links stress from effects on learning and memory to neurodegenerative diseases, such as Alzheimer’s.

See also: Division of labour and the evolution of multicellularity

In conclusion, in this paper we present a model showing that multicellularity and cellular differentiation can develop when cells can form an aggregate that enables them to exchange chemical signals and metabolites. This aggregate essentially has a higher physiological dimension, so that when there are cellular processes that are incompatible in a single cell, segregation of these processes into separate cells is possible in the aggregate form. Regulatory mechanisms that can control such a division of labour within an aggregate can be expected in many ancestral unicellular forms and are based on signals coming either from the cell itself, or from partner cells in the aggregate environment. The resulting division of labour can generate fitness benefits that lead to selection on the propensity of cells to aggregate, and hence to form multicellular and differentiated organisms.

My comment: They fail to include any facts about how the innate immune system. Their conclusion links the energy-dependent exchange of chemical signals from nutrients and their metabolites to genetic networks that link regulatory mechanisms to the division of labor and multicellularity outside the context of biophysically constrained RNA-mediated protein folding chemistry and the nutrient-dependent stability of organized genomes.  In the first quarter of the last century, the stability of organized genomes was linked by Hugo de Vries definition of “mutation” to the jump-like changes in morphology that population geneticists and other biologically uninformed non-scientists could readily observe.  Assumptions about their observations led to the invention of neo-Darwinism, which made Darwin’s “conditions of life” secondary conditions. Natural selection was the primary consideration, which allowed claims to be made about mutations and evolution.
We now see what happens when anything is assumed without consideration for stress-perturbed “conditions of life.”  But, it’s too late.
The predictability of molecular evolution during functional innovation has repeatedly been placed into the context of biophysically constrained nutrient energy-dependent RNA-mediated DNA repair without acknowledging the role of  virus-driven pathology, which prevents ecological variation from linking Darwin’s “conditions of life” to ecological adaptation and all biomass and all biodiversity.
The energy-dependent predictability of hydrogen-atom transfer in DNA base pairs in solution, which links supercoiled DNA to protection against virus-driven entropy in all organisms with organized genomes, is missing in representations of molecular evolution that predictably must involve de novo gene creation and functional innovation.  When nutrient-dependent de novo gene creation and RNA-mediated DNA repair are not considered, what we have is an example of the magic of molecular evolution. If molecules automagically evolve, the molecules can be linked to the evolution of everything else. Proteins can evolve! Multicellularity can evolve! Sexually differentiated cell types can evolve! All cell type differences can evolve! People can evolve!
Evolution became predictable based on the ignorance of energy-dependent cell type differentiation that links hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA via nutrient-dependent RNA-mediated gene duplication and amino acid substitutions that repair virus-damaged DNA.  Cell type differentiation that is obviously controlled by the physiology of reproduction was removed from Darwin’s “conditions of life” and — before most people knew it — they were left with pseudoscientific nonsense based on a definition and the assumptions of the biologically uninformed.

Regaining the ability to grow in the absence of this gene requires the evolution of a new function that allows sufficient amounts of serine to be made to support cell growth. Although this experimental system does not necessarily recapitulate natural evolutionary scenarios, many aspects of this design are reflective of ecological and evolutionary features found in more natural circumstances.

See also: Serine
My comment: Serine is a protein-building amino acid.  Protein building requires controlled thermodynamic cycles protein biosynthesis and degradation. Although serine is not essential in the human diet because it is synthesized via typical intercellular interactions, the human ability to produce the amino acid serine and its effect on protein folding did not automagically arise in the absence of amino acid substitutions in other species that stabilized their genomes in the context of nutrient-dependent pheromone-controlled ecological adaptations.
If serious scientists had tried to link energy-dependent changes in base pairs to amino acid substitutions that prevent neurodegenerative diseases such as Alzheimer’s, most people would have focused on prevention and minimally expensive dietary supplements in attempts to prevent the stress-induced viral replication that has just been reported to cause Alzheimer’s.

See also:  Microbes and Alzheimer’s Disease

See also: On epigenetics: We are not just our DNA

My comment (awaiting moderation): Thanks for reporting on the symposium presentation.
In the early 1990’s Bruce McEwen told me to start with gene activation if I wanted anyone to validate my mammalian model. It developed into a model that now links energy-dependent hydrogen-atom transfer in DNA base pairs in solution from RNA-mediated DNA repair to supercoiled DNA that protects the organized genomes of all living genera from virus-driven entropy.
The symposium validated my model in the context of what has since been learned about transgenerational epigentic inheritance of the Zika virus, and the virus-driven pathology of Alzheimer’s disease.
Simply put, the nutrient-dependent innate immune system links RNA-mediated DNA repair to healthy longevity or virus-driven energy theft to all pathology via what is currently known about biophysically constrained protein folding chemistry and the physiology of nutrient-dependent reproduction.



RNA methylation, RNA-directed DNA methylation, learning and memory

sink testing

Lab medicine The illegal practice of providing false test results on clinical specimens–eg, vials of blood, urine specimens, that were deliberately discarded–ie, down the sink, without actually testing them

Pylori Story #1: Acid Attack

Pylori Story #2: Journey to the Center of the Stomach

The “Modern Synthesis” is analogous to sink testing in the medical laboratory.

See for example: Replace the Modern Synthesis (Neo-Darwinism): An Interview With Denis Noble


[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. The anglophone tradition was taught. I was taught, and so were my contemporaries, and so were the younger scientists. Evolution was defined as “changes in gene frequencies in natural populations.” The accumulation of genetic mutations was touted to be enough to change one species to another…. No, it wasn’t dishonesty. I think it was wish fulfillment and social momentum. Assumptions, made but not verified, were taught as fact.

The assumptions that were taught as fact led to this revelation: “It was really surprising,” Dr. Bernstein said. “Why would a metabolism gene cause cancer?”

The facts about biologically-based nutrient-dependent RNA-mediated cell type differentiation, which is perturbed by viruses, led to this revelation:

See for example: Breath Test for Stomach Cancer
My comment: The test for H. pylori is one of the simplest tests to perform in the lab. The breath test for stomach cancer will link gut bacteria from metabolic networks to genetic networks in all invertebrates and vertebrates via what is currently known about RNA-mediated cell type differentiation and the stability of all organized genomes in all living genera.
DNA methylation changes in plasticity genes accompany the formation and maintenance of memory

The ability to form memories is a prerequisite for an organism’s behavioral adaptation to environmental changes. At the molecular level, the acquisition and maintenance of memory requires changes in chromatin modifications. In an effort to unravel the epigenetic network underlying both short- and long-term memory, we examined chromatin modification changes in two distinct mouse brain regions, two cell types and three time points before and after contextual learning. We found that histone modifications predominantly changed during memory acquisition and correlated surprisingly little with changes in gene expression. Although long-lasting changes were almost exclusive to neurons, learning-related histone modification and DNA methylation changes also occurred in non-neuronal cell types, suggesting a functional role for non-neuronal cells in epigenetic learning. Finally, our data provide evidence for a molecular framework of memory acquisition and maintenance, wherein DNA methylation could alter the expression and splicing of genes involved in functional plasticity and synaptic wiring.

See also: Search Results for ‘RNA-directed DNA methylation’

I don’t think this will become clearer.

  1. Base pair changes are nutrient energy-dependent
  2. RNA-directed DNA methylation is nutrient-dependent
  3. RNA-mediated amino acid substitutions are nutrient-dependent
  4. Alternative splicings of microRNAs are nutrient-dependent
  5. Chromatin modification is nutrient-dependent
  6. Histone modifications are nutrient-dependent
  7. Plasticity is nutrient-dependent
  8. DNA repair is nutrient-dependent
  9. Ecological adaptation is nutrient-dependent


  1. Nutrient-dependent epigenetically-effected learning and memory links RNA-directed DNA methylation from microRNAs to cell adhesion proteins and supercoiled DNA in the organized genomes of all living genera.
  2. Alternative splicings of microRNAs are linked from the microRNA/messenger RNA balance to learning and memory via amino acid substitutions in the histones of supercoiled DNA .
  3. Viruses steal the nutrient energy that links the perturbed microRNA/messenger RNA balance to mutation-driven pathology.

See also: Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements

This study demonstrates that decoupling transcriptional changes from post-transcriptional changes and integrating them with epigenetic alterations in a computational framework can elucidate the transcriptional network that tunes and amplifies the effect of miRNA loss. The computational framework introduced here may benefit studies of miRNAs by shifting emphasis to the rewired transcriptional networks that cause the majority of the transcript-level changes.

Re: “…the rewired transcriptional networks that cause the majority of the transcript-level changes.” They link the nutrient-dependent pheromone-controlled physiology of reproduction to weekend evolution of the bactrerial flagellum.
See: Evolutionary Rewiring

The results highlight the importance of gene duplication in evolution, said Hughes, and the ability of the resulting diverged proteins to “moonlight” in roles aside from their main function. Indeed, said Jeff Barrick of the University of Texas in Austin who was not involved in the work, such cross-talk gives organisms “greater robustness,” allowing them “to restore a function even though they are missing a genetic part.”

My comment: Indeed, Barrick makes no mention of his own work with Richard Lenski, like this one:
Large Chromosomal Rearrangements during a Long-Term Evolution Experiment with Escherichia coli

IMPORTANCE Bacterial chromosomes are dynamic structures shaped by long histories of evolution.

My comment: The long histories were just reduced to the history of weekend evolution of the bacterial flagellum via nutrient-dependent pheromone controlled chromosomal rearrangements.


Life history transitions and RNA-mediated survial

The Endospore-Forming Pathogen Bacillus cereus Exploits a Small Colony Variant-Based Diversification Strategy in Response to Aminoglycoside Exposure


Thus, consideration of SCVs as a new, yet unexplored lifestyle of B. cereus within the common ecological niches, in which antibiotic-active substances produced by competitive microorganisms, plants, and invertebrate/vertebrate vectors might potentially also induce this persistent life-form of B. cereus, opens a panoply of research questions to be followed up.

Reported as:

Lifestyle switching – Bacillus cereus is able to resist certain antibiotic therapies


This newly discovered mechanism may provide an alternative explanation for antibiotic resistance.

My comment: They report the conserved molecular mechanisms of RNA-mediated gene duplication and RNA-mediated amino acid substitutions that link nutrient-dependent changes in the microRNA/messenger RNA balance from adhesion proteins to the supercoiled DNA. Supercoiled DNA protects all organized genome from virus-driven entropy in the context of transgenerational epigenetic inheritance linked from NORAD to ecological, social, neurogenic, and socio-cognitive niche construction via the the events we detailed in the molecular epigenetics section of our 1996 Hormones and Behavior review.
Neo-Darwinian ideas about mutation-driven evolution have again been replaced by experimental evidence of biologically-based cause and effect. This evidence, like all other experimental evidence that link atoms to ecosystems via nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation, adds another layer of arguments to those that should by now have eliminated all assumptions about evolution from discussion among all scientists.
The fact that pseudoscientists seem relatively uninterested in examining experimental evidence like this, allows them to first be placed into the category of those who are biologically uninformed before categorizing them as biologically uninformed science idiots when they refuse to admit what experimental evidence of biologically-based cause and effect consistently has proved.
It proves that protected populations of neo-Darwinian theorists living in academia are among the most ignorant of all human populations that have ever existed, which is why all theorists are becoming extinct.
For example, the news article explains the development of an Environmental niche to cope with stress. Niche construction is fine-tuned by chemical gradients that must be sensed, and the secretion of nutrient-dependent signals to others so that the communication of information — lots of communication, and lots of information — links niche construction to survival of all species via their innate ability to adapt by making the right choices. The experiments of Richard Lenski, for comparison, link survival of different strains of bacteria to mutations and evolution.
See for instance: The Man Who Bottled Evolution
See for comparison: A Cellular System for Spatial Signal Decoding in Chemical Gradients and Noncoding RNA –NORAD– Regulates Genomic Stability by Sequestering PUMILIO Proteins.
Note however, NORAD in the context of RNA-mediated strategic cellular defense is not rocket science. Hopefully, neo-Darwinian theorists will not link it to the Cuban Missile Crisis and dismiss it as if the threat of antibiotic resistance was not the one that could readily lead to the extinction of all serious scientists — and everyone else on this planet. But, if it seems to be too late for you to challenge a theorist, nevermind. You’re probably right; they may have doomed us all to death by evolutionary theory.


Ecological adaptations you cannot live without

Follow up to: Stress-perturbed mitochondrial dysfunction
Summary: Bruce McEwen and others are taking the concept of RNA-mediated amino acid substitutions in cell type differentiation to a new level. They will force neo-Darwinian theorists to differentiate between mutations and amino acid substitutions. After February 14, 2016, if you still don’t know the difference, you may be subjected to ridicule by serious scientists who know how to link atoms to ecosystems in the context of biologically-based cause and effect.
Also, the “Precision Medicine Initiative” links metabolic networks and genetic networks via RNA-mediated amino acid substitutions. Virus-perturbed mitochrondrial energy function cannot be linked from mutations to increasing organismal complexity, and neo-Darwinian theorists appear to have no fall-back position. They seem to have bet everything on de Vries definition of mutation and their assumptions about how long the accumulation of mutations might take to cause the evolution of a new species. If you are in the USA and were not taught to believe in that pseudoscientific nonsense, you will have a nicer Valentine’s Day.
Evidence of a genetic ‘fountain of youth’ discovered is the most recent story about biologically-based RNA-mediated cell type differentiation, which is linked to life extension and increased vitality via nutrient energy-dependent RNA-mediated amino-acid substitutions. The coordinating author of the recently published study is a “Professor of Energy Metabolism at ETH Zurich.” Nutrient energy-dependent metabolic networks are linked to genetic networks via RNA-mediated events linked from gene duplication and gene expression to cell type differentiation and ecological speciation via the physiology of reproduction.


it is helpful to have a basic understanding of how genes are expressed. A measure of gene expression can be found in the number of its mRNA molecules present in an animal’s cells. When the mRNA of a certain gene is widespread, that gene is being upregulated and when it is scarce, the expression of the gene is minimal. Using statistical models, the researchers looked for the intersection of genes that were regulated in the same manner across the different life stages of all three animals. Out of 40,000 genes shared by the organisms, the researchers identified a mere 30 that were significant markers for aging.

The journal article was published as: Branched-chain amino acid catabolism is a conserved regulator of physiological ageing, which is available for free.
My comment: The article shows that branched-chain amino acids (BCAAs) alter a nutrient-dependent neuroendocrine signal, which impacts lifespan via receptor-mediated events. The amino acids clearly link the innate immune system via microRNAs, heat shock proteins, and cell adhesion proteins to the de novo creation of the receptors that protect organized genomes from virus-driven entropy in an experience-dependent cell type non-autonomous manner. Transcription factors control epistatic synergy, which is how the transcription factors modulate physiological aging.
Extended nutrient-dependent healthspan is linked from the pheromone-controlled life history transitions of nematodes across species from microbes to humans via the RNA-mediated amino acid substitutions that differentiate the cell types of all individuals of all species.
Journal article excerpt:

Lastly and consistent with previous findings in rodents, nutritional supplementation of BCAAs extends nematodal lifespan. Taken together, BCAAs act as periphery-derived metabokines that induce a central neuro-endocrine response, culminating in extended healthspan.

Journal article conclusion (with my emphasis):

Since daf-7 is expressed in ASI neurons only30, while its receptors daf-1 and daf-4 act in the periphery49, daf-7/TGFβ may now be considered to act cell-non-autonomous as a neuro-endocrine hormone that impairs lifespan in otherwise healthy animals in response to evolutionary conserved pathways and amino acid signals derived thereof (Fig. 9g).

My comment: The obvious need to link atoms to ecosystems via nutrient energy-dependent life was removed when they placed their experimental evidence into the context of “evolutionary conserved pathways.” Instead of conserved molecular mechanisms, they claim that evolutionary conserved pathways automagically link atoms to ecosystems in the context of population genetics and ridiculous theories based on neo-Darwinian concepts. Neo-Darwinists also link accumulated mutations to the evolution of different species.
De Vries 1904 definition of “mutation” is typically included in articles that clearly link what is known about biophysically constrained RNA-mediated protein folding chemistry to nutrient-dependent amino acid substitutions. The substitutions link the epigenetic landscape to the physical landscape of supercoiled DNA via microRNAs and cell adhesion proteins that stabilize organized genomes in all living genera.
Neo-Darwinists seem unable to grasp the fact that there are obvious differences between mutations, which linked to pathology and amino acid substitutions, which are linked to nutrient-dependent healthy longevity.

See: What is Life?


We know definitely, today, that Darwin was mistaken in regarding the small, continuous, accidental variations, that are bound to occur even in the most homogeneous population, as the material on which natural selection works. For it has been proved that they are not inherited.

My comment: More than 70 years later, all serious scientists know that the accidental variations, which are still called mutations, contribute to virus-driven genomic entropy. Viruses steal the energy that is required for nutrient-dependent RNA-mediated cell type differentiation in the context of the physiology of reproduction in all living genera. Simply put, viruses are linked to loss of function and the loss of genes. Human life appears to involve the nutrient-dependent de novo creation of at least a few thousand genes that we cannot live without.

The 3230 genes you can’t do without


Among all those genes, the researchers found 10 million variants—places within genes that varied from person to person.

My comment: A report about the nutrient-dependent substitution of achiral glycine in position six of the GnRH decapeptide links the substitution from the epigenetic effects of food odors and pheromones on the physiology of reproduction to the stability of vertebrate genomes via metabolic networks, genetic networks, and supercoiled DNA, which probably protects organized genomes from virus-driven entropy.
See:Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor
Excerpt (with my emphasis):

It is very surprising and fascinating that the coordinated evolutionary selection of amino acids participating in binding GnRH has resulted in such perfection, that no substitution with a natural amino acid in any position improves binding potency.

My comment: What he calls “coordinated evolutionary selection of amino acids” requires fixation of nutrient-dependent RNA-mediated amino acid substitutions in organized genomes, which occurs only in the context of the physiology of reproduction. It will be interesting to see how many essential genes from the forthcoming report can be placed into the context of this report:  Feedback loops link odor and pheromone signaling with reproduction.

At least 10,000 neurons in 26 different brain areas appear to transmit signals directly to GnRH neurons.

My comment: Nutrient-dependent pheromone-controlled fixation of RNA-mediated amino acid substitutions must have occurred in many of the neurons that transmit signals directly to GnRH neurons. If fixation had not occurred, the stability of organized vertebrate genomes could not have been achieved.
For comparison, if the 10 million variants in the 10,000 neurons in these 26 different brain areas linked mutations to the development of the human brain, biologically uninformed science idiots could claim that the human brain evolved via a series of mutations in the genes of microbes that also led to the evolution of human morphological and behavioral diversity. However, no information that links biologically-based cause and effect includes experimental evidence that links mutations to the 10 million variants in the 10,000 neurons in these 26 different brain areas. All experimental evidence of biologically-based cause and effect links Schrodinger’s claims from 1944 to non-Darwinian cell evolution. which exemplifies ecological adaptation.
Indeed, the latest articles to report on non-Darwinian cell evolution in cancer tissues, links nutrient-dependent supercoiled DNA to protection from virus-driven genomic entropy and pathology.
Virus-driven pathology: Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity
Protection from virus-perturbed protein folding Structural diversity of supercoiled DNA
My comment: Nutrient-dependent microRNAs link supercoiled DNA from mitochondrial function via metabolic networks and genetic networks:
See: Mitochondrial functions modulate neuroendocrine, metabolic, inflammatory, and transcriptional responses to acute psychological stress
Excerpt (with my emphasis):

In mice with WT mitochondria, stress significantly decreased circulating levels for 13 (65%) of the 20 amino acids investigated (Fig. S3).

My comment: The stress is readily linked to the proliferation of viruses. The viruses steal the nutrient energy that is required for DNA repair and biophysically constrained RNA-mediated protein folding chemistry. Perturbed thermodynamic cycles of protein biosynthesis and degradation link the viruses from energy theft to decreased levels of circulating amino acids, which are essential to the stability of organized genomes in all living genera. The microRNA/messenger RNA balance is linked from RNA-mediated protein folding chemistry to supercoiled DNA and protection of organized genomes except when stress alters the molecular mechanisms that are required for DNA repair.
For example, see: MicroRNAs: From Female Fertility, Germ Cells, and Stem Cells to Cancer in Humans
See also: The Bull Sperm MicroRNAome and the Effect of Fescue Toxicosis on Sperm MicroRNA Expression
My comment: Despite what is known about the links from branch-chained amino acids to mitochondria-driven metabolic and genetic networks, the fact that a single amino acid substitution is linked to the virulence of viruses via the theft of energy seems to be ignored.
See: Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution
Excerpt: The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site.
My comment: Nutrient-dependent microRNAs are linked to RNA-mediated via DNA repair, which is linked to ecological adaptations that you cannot live without.

amino acid homeostasis

Receptor methylation controls behavior

The protein arginine methyltransferase PRMT5 promotes D2-like dopamine receptor signaling

Excerpt 1)

The addition of a methyl group to an arginine residue can remove a hydrogen bond donor and decrease the electrostatic surface potential at the residue, resulting in a change in size and hydrophobicity that can affect its interaction with binding partners (21).

Excerpt 2)

Together, these results led us to propose that arginine methylation promotes D2-like dopamine receptor signaling and that this mechanism of receptor regulation is conserved between nematodes and humans. Moreover, our finding that several hundred mammalian GPCRs contain predicted methylation sites within their cytoplasmic domains (Fig. 1A and tables S1 and S2) suggests that methylation may broadly regulate GPCR signaling in a previously unappreciated manner.

My comment: This article links RNA-directed DNA methylation to G protein-coupled receptors via biophysically constrained nutrient-dependent pheromone-controlled protein folding chemistry in species from nematodes to humans. It was reported as:

Receptor methylation controls behavior

D2 dopamine receptors are targeted by antipsychotic agents to regulate behavior. Likhite et al. found putative arginine methylation motifs in some human G protein–coupled receptors (GPCRs), including the D2 dopamine receptor, and in homologs in the worm Caenorhabditis elegans. Methylation of the D2 dopamine receptor by the arginine methyltransferase PRMT5 enhanced D2 receptor signaling in cultured cells. C. elegans lacking prmt-5 had behavioral problems similar to those in worms deficient in the D2-like receptor DOP-3. Thus, methylation of GPCRs may be important for clinically relevant targets such as the D2 receptor.

My comment: The claim that Receptor methylation controls behavior can be placed into the context of MicroRNA-encoded behavior in Drosophila, and all other living genera. For example, Feedback loops link odor and pheromone signaling with reproduction.

Indications that GnRH peptide plays an important role in the control of sexual behaviors suggest that pheromone effects on these behaviors might also involve GnRH neurons. (p 683)

My comment: The nutrient-dependent microRNA/messenger RNA balance links energy-dependent base pair changes to RNA-mediated gene duplication and fixation of RNA-mediated amino acid substitutions that differentiate all cell types of all individuals of all living genera in the context of the physiology of reproduction. Even when the physiology of reproduction does not involve neurons, it involves the conserved molecular mechanisms of nutrient-dependent pheromone-controlled reproduction in species from microbes to humans.
See for details: From Fertilization to Adult Sexual Behavior

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: The alternative splicing of otherwise identical genes links everything known about physics, chemistry, and biology via the conserved molecular mechanisms of biophysically constrained nutrient-dependent RNA-mediated protein folding to protection against virus-driven genomic entropy, which is ensured by supercoiled DNA.


Models are not theories (2)

MicroRNA-encoded behavior in Drosophila

Editor’s summary:

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene activity. They repress expression through complementary base pairing interactions with target messenger RNAs. MiRNAs are involved in regulating many cell and developmental processes. Picao-Osorio et al. find that miRNAs can also control behavior in the fruit fly Drosophila.

My comment: Ridiculous claims from 1) We are all mutants and from 2) Mutation-Driven Evolution can now be placed into the context of what is known to serious scientists about biophysically constrained nutrient-dependent protein folding chemistry, which is RNA-mediated.

Ridiculous claim #1) “We are all mutants”
Ridiculous claim #2) “…constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world.”

Anyone who was taught to believe in the pseudoscientific nonsense that is expressed in those ridiculous claims cannot become a serious scientist until they evaluate the established scientific truth about MicroRNA-encoded behavior in Drosophila.
The truth links nutritional epigenetics to energy-dependent RNA-mediated cell type differentiation. RNA-mediated amino acid substitutions stabilize cell type differentiation that is perturbed by viruses. Viruses steal the nutrient energy that cell types require to support the healthy longevity of all organisms.
Healthy organized genomes are protected from genomic entropy via the physiology of reproduction, which links microRNAs and the behavior of all organisms from atoms to ecosystems to fixation of amino acid substitutions in supercoiled DNA. RNA-directed DNA methylation links RNA-mediated gene duplication and RNA-mediated fixation of amino acid substitutions to receptor mediated behaviors. The link from microRNAs to receptor mediated behaviors has been missing. Serious scientists knew the missing link would be found because they knew that de novo gene creation is nutrient energy-dependent. Pseudoscientist are still trying to eliminate the need for the nutrient dependent de novo gene creation. They replaced de novo gene creation with mutations and natural selection, and are still trying to keep people from realizing how much neo-Darwinian nonsense they have been touting in this century.
See: The bioenergetic costs of a gene

These results eliminate the need to invoke an energetics barrier to genome complexity.

My comment: What kind of fool thinks he can eliminate the need to link nutrient energy to genome complexity via the conserved molecular mechanisms of biophysically constrained RNA-mediated protein folding chemistry in all living genera?


Can veterans and other prisoners escape pseudoscience?

Combating Evolution to Fight Disease

“…an important gap is being filled by molecular understanding of the genesis of variation that confers the ability to evolve.”

Inside the drive to collect DNA from 1 million veterans and revolutionize medicine

Excerpt 1)

The U.S. Department of Veterans Affairs is gathering blood from 1 million veterans to sequence their DNA. This is one of the most ambitious projects ever undertaken to understand our genome.

Excerpt 2)

In January, President Obama announced plans for the Precision Medicine Initiative, which will create a database with over 1 million participants.

My comment: The existing database is already sufficient to link what is currently known about biophysically constrained nutrient-dependent RNA-mediated cell type differentiation to specific amino acid substitutions that predict how many different individuals will respond to many different types of medications. See: Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing, which was reported in the context of this video representation.

See also:

See also:  Evolution of MicroRNA Research Over the Past Decade

More than 20,000 microRNA-Focused Publications Were Assessed as a Means to Characterize the Field

Summary: Nutrient-dependent microRNAs are linked from cell adhesion proteins to supercoiled DNA via an atoms to ecosystems model of protection from virus-driven genomic entropy, which is manifested in all pathology.
The octopus genome and the evolution of cephalopod neural and morphological novelties linked the conserved molecular mechanisms of RNA-mediated gene duplication and RNA-mediated amino acid substitutions from microRNAs  and cell adhesion proteins to cell type differentiation in species from microbes to humans.
No new code makes reprogramming cells possible — despite the claims of cancer researchers. Nothing about the code is new. Experience-driven de novo creation of genes is linked to virus-perturbed loss of function and pathology via what is known about cell type differentiation.
Cell type differentiation is nutrient-dependent and the availability of nutrients links ecological variation to ecological adaptation only when virus-driven pathology is controlled by nutrient-dependent microRNAs that link supercoiled DNA to protection against virus-driven genomic entropy.


Mutated mitochondrial genes vs Supercoiled DNA

Genetics probe identifies new Galapagos tortoise species

Excerpt 1)

Their paper1, published in PLoS ONE on 21 October, is the culmination of a decade of work. It presents 25 mitochondrial DNA mutations that reliably separate the two groups.

Excerpt 2)

“The species concept is a fuzzy one,” he says. “Call them whatever you want, I don’t care. What is important is that people realize there is hidden diversity.”

My comment: The editors at “Nature” seem to typically support the misrepresentations of the title: new Galapagos tortoise species,  despite accurate claims that “The species concept is a fuzzy one.”
Let’s compare what we see this week in “Nature” to what we see in “Science.”
Is the nature of “Nature” pseudoscience? Is “Systems biology” what’s important to “Science?”

Systems biology (un)certainties


Models are simplified (but not simplistic) representations of real systems, and this is precisely the property that makes them attractive to explore the consequences of our assumptions, and to identify where we lack understanding of the principles governing a biological system.

My comment: (published to the “Science” site)

Is anything less than this atoms to ecosystems approach to modeling biologically-based cause and effect going to be acceptable from this point forward?
What this article suggests to me is that others must develop models based on nutrient-energy dependent base pair changes, or that their models cannot be validated with experimental evidence.
Structural diversity of supercoiled DNA
Re: “comparisons of supercoiling-dependent twisted, writhed, curved, and kinked conformations and associated base exposure. Each of these structural features may be differentially recognized by the proteins, nucleic acids, and small molecules that modulate DNA metabolic processes.”

Summary: Claims that mutations in mitochondrial genes led to the biodiversity manifested in Galapagos tortoise species, or any other species should be evaluated in the context of this question: “Is there a model for that?”
If no model of biologically-based cause and effect links mutations in mitochondrial genes to RNA-mediated gene duplication and RNA-mediated amino acid substitutions, the mutations cannot be placed into the context of anything known about nutrient-dependent RNA-mediated cell type differentiation in species from microbes to man, which is controlled by the physiology of reproduction.
Also, ask yourself, would a serious scientist who understands RNA-mediated gene silencing or any other aspect of RNA-mediated epigenetic regulation of gene expression claim that mutations in mitochondrial genes led to anything except pathology?