Summary: Light-induced amino acid substitutions link cell type differentiation in plants to nutrient-dependent pheromone-controlled reproduction in animals via the biophysically constrained chemistry of protein folding. Protein folding is perturbed by mutations that limit the ability of organisms to adapt to ecological variation. Viruses contribute to mutations. The sun’s biological energy appears to supply the anti-entropic force that links entropic elasticity to the development of successful morphological and behavioral phenotypes that are exemplified in extant versus extinct biodiversity. The importance of the anti-entropic force seems to have gone virtually unnoticed by theoretical physicists and evolutionary theorists who argue for “Big Bang” cosmology and mutation-driven evolution in the context of the evo-devo debate.
Abstract excerpt: “The widely accepted view was that morphological changes resulted from differences in number and/or type of transcription factors, or even from small changes in the amino acid sequence of similar proteins.
Excerpt: “Fig. 1. Schematic representation of a gene with its cis-regulatory elements (CREs) and the potential mutations that can affect transcriptional processes.
My comment: The “widely accepted view” of cell type differentiation confuses the effects of mutations, which perturb protein folding, and RNA-mediated amino acid substitutions that stabilize it. Serious scientists now realize the need for links from epigenesis to epistasis. Many are slow to realize that no link from ecological variation to ecological adaptation has been suggested in discussion about evolutionary theories. See for instance:
Excerpt 1) “Future work should try to address the changing relationship between the epigenome and genome over the lifespan of the cell, in different phases of the cell cycle and across cellular generations. Other factors that modulate chromatin organization also remain to be investigated — the proteins responsible for chromatin remodelling, for example, and the chaperone proteins associated with histone variants that control assembly and disassembly of chromatin14.”
Excerpt 2) ” “A case in point is modification of the amino-acid residue lysine 27 (K27) on histone H3 in chromatin. Addition of an acetyl group (a modification known as H3K27ac) correlates with transcription of the corresponding region of DNA, whereas trimethylation (H3K27me3) is linked to transcriptional repression.”
My comment: The proteins responsible for chromatin remodelling are nutrient dependent and the chaperones help to buffer the nutrient stress, which is typically accompanied by social stress, during changes in ecology that lead to successful ecological adaptation of individuals and some species.
See also: Cas9 specifies functional viral targets during CRISPR–Cas adaptation. It was published (in advance) in the same issue of “Nature” that contains the articles about Epigenomics: Roadmap for regulation.
CRISPR–Cas adaptation was reported here Virus-cutting enzyme helps bacteria remember a threat.
Excerpt: “…memories are embedded in the bacterial equivalent of an adaptive immune system capable of discerning helpful from harmful viruses called a CRISPR (clustered regularly interspaced short palindromic repeats) system. It works by altering the bacterium’s genome, adding short viral sequences called spacers in between the repeating DNA sequences. These spacers form the memories of past invaders. They serve as guides for enzymes encoded by CRISPR-associated genes (Cas), which seek out and destroy those same viruses should they attempt to infect the bacterium again.”
My comment: There is no mention of the fact that the enzymes do not automagically appear with their ability to enable the destruction of harmful viruses. In the representation above, there is a missing link between the epigenetic landscape and the physical landscape of DNA in the organized genomes of species from microbes to man. That missing link is the sun’s biological energy, which is the source of all nutrition. Nutrient-uptake links the biological energy from the sun to metabolic networks and to genetic networks that might otherwise be perturbed by harmful viruses that cause mutations.
The importance of nutritional epigenetics must be considered in any attempt to explain evolutionary theory, or to accurately represent how ecological variation leads to ecological adaptations via the anti-entropic epigenetic effect of the sun’s biological energy on cell type differentiation. Too much sun exposure, for example, can lead to mutations and skin cancer. But why just skin cancer? And why does some sun exposure seem to lead to vitamin-D production that stabilizes the organized genome of human populations in areas where malaria is endemic. Those were among the questions I answered in an invited review of nutritional epigenetics. Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems. Others have since become interested in answering those questions.
Excerpt: “… liver, colorectal and lymphocyte malignancies present more mutations in some parts of our chromosomes, while breast, ovarian and lung cancers accumulate more mutations in other places.”
My comments: That is the basis for the claims I made in the context of nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all species.
Amino acid substitutions stabilize DNA in organized genomes. Mutations perturb the biophysically constrained chemistry of protein folding that leads from entropic elasticity to anti-entropic epistasis and to the phenotypes exemplified in morphological and behavioral diversity of species from microbes to man.See for examples: Nutrient-dependent/pheromone-controlled adaptive evolution: a model. It led to the invitation to submit the invited review on nutritional epigenetics.
See for criticisms of the model by someone who believes in beneficial mutations:Criticisms of the nutrient-dependent pheromone-controlled evolutionary model.
In my model of ecological adaptations, the obvious links from food odors to thermodynamic cycles of protein biosynthesis and degradation are typically controlled by nutrient uptake, which links ecological variation to ecological adaptation via enzymes that metabolize nutrients to species-specific pheromones. Adaptations across a continuum of increasing organismal complexity link epigenetically-effected brain development in insects to humans during their life history transitions. S. cerevisiae is the model organism linked to stem cell activation, and in my model it also sets the stage for explanations of the nutrient-dependent pheromone-controlled RNA-mediated events. See: Predicting phenotypic variation in yeast from individual genome sequences and From Fertilization to Adult Sexual Behavior and Organizational and activational effects of hormones on insect behavior.
The aspects of organization and activation of behavior do not address the origins of life, which typically have been linked to mutations across billions of years. See for instance:
Abstract excerpt: “…bridges billions of years of evolutionary divergence and provides an example of an RNA structure-based translation initiation signal capable of operating in two domains of life.
Excerpt: “…the CU scientists and their colleagues “have shown for the first time that a bona fide signal in an RNA structure promotes protein synthesis in the two domains of life.”
My comment: What they’ve shown includes the anti-entropic epigenetic effect of light-induced amino acid substitutions in all domains and on all cell types of all individuals of all species of all kingdoms. Their report can be placed into the context of A universal trend of amino acid gain and loss in protein evolution.
Excerpt: “We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms.”
My comment: That universal, intrinsic, anti-entropic trend is RNA-mediated by light-induced amino acid substitutions that stabilize DNA in the organized genomes of species from microbes to man. Indeed, the journal article suggests: “That a compact IRES RNA can use this primitive mechanism suggests that RNA structure-driven or structure-assisted initiation may be used in potentially all domains of life, driven by diverse RNAs…”
The obvious link across all domains of life is not mutations and evolution across billions of years. It is nutrient-dependent amino acid substitutions. RNA-mediated cell type differentiation incorporates what is currently known about physics, chemistry, and information. Without that transfer of information across all three domains and all kingdoms, ecological variation cannot be linked from atoms to ecosystems via epigenesis and epistasis.
Light-induced amino acid substitutions in plants, algae, and sea slugs link the stability of DNA in the context of biologically-based top-down causation and anti-entropic epigenetic effects linked to increasing organismal complexity via the physiology of reproduction, which enables the fixation of the amino acid substitutions.
The manifestations of anti-entropic light and the RNA-mediated fixed amino acid substitutions in the morphological and behavioral phenotypes and in the biodiversity of species from microbes to man may be somewhat unnerving to those who think they have discovered the biological basis for life in all domains. That may explain why these authors did not include any speculation about the across-kingdom link via the microRNA/messenger RNA balance. That across-kingdom link must be addressed, if serious scientists ever intend to make scientific progress based on experimental evidence of biologically-based cause and effect. See for example:
Combined agonist–antagonist genome-wide functional screening identifies broadly active antiviral microRNAs
Excerpt: “Since the discovery of the first microRNA (miRNA) in Caenorhabditis elegans, research in diverse organisms has illuminated the role of this class of small RNA in a wide range of cellular processes (reviewed in ref. 1). MicroRNAs modulate the expression of specific genes by guiding the RNA-induced silencing complex (RISC) to complementary sites within messenger RNAs (mRNAs) (2). This generally serves to down-regulate target genes at specific times, in concert with other regulatory mechanisms in the cell (reviewed in ref. 3).”
My comment: The miRNA/mRNA balance appears to be perturbed by viral miRNAs — unless it is well-maintained by nutrient uptake and RNA-directed DNA methylation. In my invited review of nutritional epigenetics, I wrote:
“Experimental evidence continues to add support for the role of ecological variation and nutrient-dependent epigenetically-effected ecological adaptations that occur via amino acid substitutions, which determine the cell types of individuals in all species. More substantial support for epigenetic effects on cell type differentiation comes from what has been learned during the past decade about the role of small non-coding RNA molecules. The small non-coding RNA molecules are called microRNAs (miRNAs). MiRNAs alter intercellular signaling by changing the balance between miRNAs and messenger RNA (mRNA) . The changes are linked to health and to pathology (Mori et al., 2014).”
In this video, cell density-dependent miRNAs are linked to cancer. Note, however, miRNA biogenesis does not appear to occur outside the biphysically constrained context of viruses and nutrient uptake. This suggests a balance between nutrient stress and viral microRNA damage must be achieved for healthy organism-level themoregulation to lead from entropic elasticity to epistasis.
Abstract: Alternative splicing (AS) is one of the key processes involved in the regulation of gene expression in eukaryotic cells. AS catalyzes the removal of intronic sequences and the joining of selected exons, thus ensuring the correct processing of the primary transcript into the mature mRNA. The combinatorial nature of AS allows a great expansion of the genome coding potential, as multiple splice-variants encoding for different proteins may arise from a single gene. Splicing is mediated by a large macromolecular complex, the spliceosome, whose activity needs a fine regulation exerted by cis-acting RNA sequence elements and trans-acting RNA binding proteins (RBP). The activity of both core spliceosomal components and accessory splicing factors is modulated by their reversible phosphorylation. The kinases and phosphatases involved in these posttranslational modifications significantly contribute to AS regulation and to its integration in the complex regulative network that controls gene expression in eukaryotic cells. Herein, we will review the major canonical and noncanonical splicing factor kinases and phosphatases, focusing on those whose activity has been implicated in the aberrant splicing events that characterize neoplastic transformation.
My comment: The complexity of epigenetically-effected alternative splicing of exons that leads from enzymes and reversible phosphorylation to gene expression has led biologically uninformed theorists to claim that cell type differentiation occurs in the context of mutations. For example, in the abstract above, mutations are clearly linked to “…the aberrant splicing events that characterize neoplastic transformation.”
By placing everything known about cell type differentiation in all cells of all individuals of all species into the context of mutations and evolution, theorists have caused the stagnation of genetic and evolutionary research. Mutations cannot be linked via perturbed protein folding and physiopathology to the physiology of health and reproduction.
Attempts to explain how evolution via mutations occurs have led to the surprising claim that “…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 (p. 199)
The idea of constraint-breaking mutation fails to link ecological variation leads to ecological adaptations via RNA-mediated amino acid substitutions. The amino acid substitutions differentiate cell type in species from microbes to man, but evolutionary theorists claim that physiopathology and ecological adaptations somehow arise via the same unexplained mechanisms. Until recently, theorists claimed that natural selection was somehow involved but even that pseudoscientific nonsense has begun to fall out of favor.
Excerpt: “Others maintain that as random mutations arise, complexity emerges as a side effect, even without natural selection to help it along. Complexity, they say, is not purely the result of millions of years of fine-tuning through natural selection—the process that Richard Dawkins famously dubbed “the blind watchmaker.” To some extent, it just happens.”
My comment: Until now, theorists only needed to claim that beneficial mutations were the key to species-wide success. Serious scientists have been required to use experimental evidence of biologically-based cause and effect that links the biological energy from the sun to the physics, chemistry, and molecular biology of life.
Fortunately, in the context of yet another report that links the epigenetic effects of light from ecological variation to ecological adaptations across species, a new model organism has emerged. See: The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing
Conclusion: “Our results open the possibility that extensive recoding is common in many organisms, rivaling alternative splicing as a means of creating functional diversity.”
Excerpt: “Does the squid have some mechanism we can learn from?”
My comment: Some people have already learned that the conserved molecular mechanisms of alternative splicing link the extensive recoding that occurs in the squid and all other species during the development of their behaviors. The squid model organism tells us is more about how quickly this extensive recoding can occur. The squid model organism of ecological adaptation does not tell us about anything that suggests extensive recoding occurs outside the context of alternative splicing. It reaffirms that fact that “…alternative splicing may be the critical source of evolutionary changes differentiating primates and humans from other creatures such as worms and flies with a similar number of genes.” — Jon Lieff (2012)
For example, in my model of ecological adaptations I’ve placed alternative splicing into the context of feedback loops and chromatin loops that link RNA-mediated amino acid substitutions to cell type differentiation of all cell types in all individuals of all species. I reiterate. See, for instance: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems.
In the squid model organism, deamination of adenosine to inosine (A-to-I) appears to link the epigenetic landscape to the physical landscape of DNA by chemically modifying the structure of mRNAs. The link from adenosine-to-inosine RNA editing to the diversity of neuronal proteomes probably integrates the changes in morphology and behavior that I attribute to changes in the miRNA/mRNA balance.
A-to-I RNA editing appears to be included in the process that alters genetic information that I detailed in my invited review of nutritional epigenetics. The unpublished review also links what is now known about viral miRNAs and nutrient-dependent miRNAs. The influence of both types of miRNAs extends across species from microbes to man via a finely-tuned atoms to ecosystems model of cell type differentiation. For example fixation of RNA-mediated amino acid substitutions occurs in the context of nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation that are epigenetically-effected by viral miRNAs.
Fixation of amino acid substitutions that differentiate cell types is perturbed by the accumulation of viral miRNAs. If, for example, viral microRNAs perturb the light-induced amino acid substitutions of luminescent bacteria in the bobtail squid, fixation of the squid’s nutrient-dependent pheromone-controlled amino acid substitutions would also be perturbed. Instead, ingestion of the luminescent bacteria is linked to more efficient foraging in the squid. The success of the squid ensures the survival of the bacteria and the survival of the squid species. See for example: A single natural nucleotide mutation alters bacterial pathogen host tropism
Excerpt 1) “For bacterial host adaptation, horizontal acquisition of a single gene regulator in the bacterial squid symbiont Vibrio fischeri was demonstrated to be an essential step in adaptation to its host28.”
Excerpt 2) “In summary, our results reporting a single naturally occurring mutation associated with a bacterial host-switching event represent a paradigm shift in the understanding of the minimal adaptations required for a bacterium to overcome species barriers and establish itself in new host populations.”
It is not a “single naturally occurring mutation.” In my model, it’s an ecological adaptation that links bioluminescent microbes from their nutrient-dependent pheromone-controlled physiology of reproduction to bioluminescence in squid and their nutrient-dependent pheromone-controlled physiology of reproduction via the biophysically constrained chemistry of protein folding that links amino acid substitutions to biodiversity in species from microbes to human.
Nutrient-stress and social stress contribute to the accumulation of viral miRNAs that would typically be prevented by nutrient-dependent pheromone-controlled feeback loops that link food odors and social odors to the nutrient-dependent physiology of reproduction via controlled changes in the miRNA/mRNA balance. The changes are manifested in transgenerational epigenetic inheritance of some physiopathology that is not always manifested in the context of metabolic networks linked to genetic networks by offspring who understand more about molecular epigenetics than their parents.
If your offspring are taught to believe in the pseudoscientific nonsense about mutations and evolution, they probably will not understand anything more than what you do about biologically-based cause and effect.That places the responsibility for “Combating Evolution to Fight Disease” on others who were not taught to believe in ridiculous theories.