Negative selection in humans and fruit flies involves synergistic epistasis
Negative selection against deleterious alleles produced by mutation influences within-population variation as the most pervasive form of natural selection.
Naturally occurring positive selection for energy-dependent codon optimality replaced every aspect of neo-Darwinian theories that linked natural selection from mutations to evolution of increasing organismal complexity. Positive selection for epigenetically-effected beneficial alleles links the epigenetic landscape to the physical landscape of supercoiled DNA via nutrient-dependent pheromone-controlled metabolic networks and genetic networks.
Everything from atoms to ecosystems was included in this invited review of nutritional epigenetics because all serious scientists know that organisms survive on food energy and that species exemplify the pheromone-controlled reproduction and chromosomal inheritance that ensures survival of all living genera.
See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
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. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man. Species diversity is a biologically-based nutrient-dependent morphological fact and species-specific pheromones control the physiology of reproduction.
See also: Transcriptome-wide Discovery of microRNA Binding Sites in Human Brain
This interactome points to functional miRNA:target pairs across >3,000 genes and represents a valuable resource for accelerating our understanding of miRNA functions in brain. We demonstrate the utility of this map for exploring clinically relevant miRNA binding sites that may facilitate the translation of genetic studies of complex neuropsychiatric diseases into therapeutics.
See also: Connections Underlying Translation and mRNA Stability
…intimate connections between mRNA and the ribosome can drive biological regulation. In closing, we consider the likelihood that these connections between protein synthesis and mRNA stability are widespread or whether other modes of regulation dominate the mRNA stability landscape in higher organisms.
No experimental evidence of evolution includes biophysically constrained biologically-based cause and effect, which integrates the required link from ecological variation to the physics, chemistry, and molecular epigenetics of what Darwin presciently linked from his “conditions of life” to ecological adaption via energy-dependent changes in messenger RNA (mRNA).
See also: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition (with my emphasis)
…the ribosome interprets two codes within the mRNA: the genetic code which specifies the amino acid sequence and a conserved “codon optimality code” that shapes mRNA stability and translation efficiency across vertebrates.
Natural selection for energy-dependent codon optimality conserves the amino acid substitutions in the context of the stability of supercoiled DNA. That stability protects all organized genomes from virus-driven energy theft and genomic entropy. Protection from viruses occurs via the pheromone-controlled biophysically constrained physiology of reproduction in all living genera. Experimental evidence of that fact was included in our section on molecular epigenetics from this 1996 Hormones and Behavior review.
From Fertilization to Adult Sexual Behavior
Parenthetically it is interesting to note even the yeast Saccharomyces cerevisiae has a gene-based equivalent of sexual orientation (i.e., a-factor and alpha-factor physiologies). These differences arise from different epigenetic modifications of an otherwise identical MAT locus (Runge and Zakian, 1996; Wu and Haber, 1995).
See for comparison: Tracing the Enterococci from Paleozoic Origins to the Hospital
Graphical abstract from “Tracing the Enterococci from Paleozoic Origins to the Hospital”
Reported as: Enterococci may have evolved antimicrobial resistance millions of years ago
…researchers have traced evidence of the bacteria’s evolutionary history back 425 million years and theorize that the same traits that allow the bacteria to thrive in hospitals likely emerged when they were carried onto land in the guts of the world’s first terrestrial animals. The study was funded in part by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
The physiology of reproduction in bacteria and all other living genera is nutrient-dependent and pheromone-controlled. Researchers who think they have traced evidence back to the bacteria’s evolutionary history across 425 million years have not considered the weekend resurrection of the bacterial flagellum to be proof of their pseudoscientific nonsense. Instead, they report “Speciation: Host energy source driven” in their graphical abstract.
Where did the energy come from?
See: Evolutionary Rewiring
The nutrient-dependent pheromone-controlled physiology of reproduction in P. fliuorescens was linked to the weekend evolution of the bacterial flagellum.
See also for an invertebrate example of nutrient energy-dependent pheromone-controlled top-down causation: Inhibition of miR-274-3p increases BmCPV replication by regulating the expression of BmCPV NS5 gene in Bombyx mori From: Virus Genes. 2017 May 10. doi: 10.1007/s11262-017-1466-7
See also: Two fatty acyl reductases involved in moth pheromone biosynthesis
Studies over the last two decades have pinpointed that the epigenetic effect of pheromone-driven adaptive evolution is one of the major factors driving the successful diversification of Lepidopteran insects10. In moths, a few substitutions in critical amino acids in the key pheromone biosynthetic enzymes are sufficient to create a novel pheromone component11,12.
Facts about pheromones in species from microbes to humans have now been placed into their proper context.
Poor human olfaction is a 19th-century myth, which was reported as: “The human sense of smell: It’s stronger than we think” May 11, 2017
See for comparison: Human pheromones: integrating neuroendocrinology and ethology
The ‘affective primacy hypothesis’  asserts that positive and negative affective reactions can be evoked with minimal stimulus input and virtually no cognitive processing. Olfactory signals seem to induce emotional reactions whether or not a chemical stimulus is consciously perceived. We theorize that the importance of human non-verbal signals is based upon information processing, which occurs in the limbic system, and without any cognitive (cortical) assessment. Affect thus does not require conscious interpretation of signal content. Underlying this fact is that affect dominates social interaction and it is the major currency in social interactions . Affective reactions can occur without extensive perceptual and cognitive encoding. They are made with greater confidence than cognitive judgments, and can be made sooner [5, 7]. Olfactory input from the social environment is well adapted to fit such assertions. For example, chemical cues allow humans to select for, and to mate for, traits of reproductive fitness that cannot be assessed simply from visual cues.
See also: The RNA Age: A Primer
What is currently known about energy-dependent biophysically constrained RNA-mediated cell type differentiation refutes every aspect of neo-Darwinian evolution by placing natural selection for codon optimality and the pheromone-controlled physiology of reproduction first.
All published works and reviews of RNA-mediated events must be placed into the context of the paradigm shift that led to the development of this game.
Cytosis: A Cell Biology Game
A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!
Some researches may continue to ignore details about energy-dependent RNA-mediated protection from virus-driven energy theft; the degradation of messenger RNA; and the pathology that is linked from mutations to the loss of enzymes, hormones and receptors in all living genera.
Others will obfuscate what is known to serious scientists.
See for comparison: Ontological Systems In Cognition
There is investigated the possibility of cognition of everything that somehow and other is able to influence to the cognizer – its Existing, which exists for him and may be cognized by him. It is proved that all parts of the Existing are interconnected, it is closed and is the only one for all cognizers in it, and everything differed from the Existing is indistinguishable for the cognizer from non-Existing and cannot be cognized by him. It is shown that the surrounding world of the cognizer, understood as a collection of objects and interconnections identified by him, corresponds to the cognizer’s `nature’ – its ontology and are only a part of the Existing. Objects and interconnections of different ontology differ from each other on level of notions, so are uncertain, inconsistent and paradoxical in relation to each other, and corresponding systems of representations with definite ontology cannot be unified in frames of one system, so are irredundant with each other. There are found the correlations of physical objects of quantum theories, also as cosmological dark matter and dark energy with objects with different ontology. There are analyzed the methods of mathematical description of objects with different ontology, the so-called `correlation principle’ of physical theories in irredundant systems of representations, the `principle of freedom’ for formation of the universe understood as the surrounding world of the cognizer. There are considered the philosophical aspects of the existence of irredundant representations, the physical picture of the world, which this concept leads to. The surrounding worlds corresponding to irredundant representation systems, being parts of the one Existing, are closely interconnected, mutually complemented and form each other, without mixing and being different `by nature’, and contradictions between them stand as moving forces of their evolution.
All aspects of anything that has ever been linked to the “moving forces” of evolution have clearly been linked from food energy and movement to biodiversity and from stress-related virus-driven energy theft to mutations that link the lack of movement at the molecular level to all pathology.
See for instance: Valerie Horsley Gets Under Skin
The Yale University cell and molecular biologist is probing the deep mysteries of epidermal cells.
See also: Brain on stress: How the social environment gets under the skin
The authors note that on page 17184, right column, first paragraph, line 4, “effect” should instead appear as “affect.”
The failure to provide a neurobiological framework for understanding natural selection for energy-dependent codon optimality, which is the basis for the biological embedding of epigenetically-effected positive health, positive affect, self-efficacy and self-esteem via effects on reactive alleles in the genome, continues to link all pathology from the virus-driven degradation of messenger RNA to the negative supercoiling of DNA.
No one asked me to establish that framework for healthy longevity or pathology, but I did it anyway after I was told to start with gene activation in GnRH neuroscrectory neurons by Bruce McEwen.
See also: Genome Digest
What researchers are learning as they sequence, map, and decode species’ genomes
The researchers found that genes involved in key survival functions, such as the removal of cellular toxins, the stabilization of proteins, and the activity of the innate immune system, were expanded in deep-sea mussels.
Anna Di Cosmo’s group presciently placed these finding into the context of General and Comparative Endocrinology in Role of olfaction in Octopus vulgaris reproduction
From the concluding paragraph:
Future work on O. vulgaris olfaction must also consider how animals acquire the odours detected by the olfactory organ and what kind of odour the olfactory organ perceives. The OL acting as control centre may be target organ for metabolic hormones such as leptin like and insulin like peptides, and olfactory organ could exert regulatory action on the OL via epigenetic effects of nutrients and pheromones on gene expression (Kohl, 2013; Elekonich and Robinson, 2000). — p. 61
The fact that the energy-dependent stability of RNA-mediated protein folding chemistry links physics from autophagy to biophysically constrained viral latency went missing during the past 4 years, but is not likely to continue to be ignored.
See why: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
…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 ‘fit’.
There is still no other model for comparison, despite the publication of Mutation-Driven Evolution on the same day my 2013 review was published.
(1) Mutation is the source of all genetic variation on which any form of evolution is dependent. Mutation is the change of genomic structure and includes nucleotide substitution, insertion/deletion, segmental gene duplication, genomic duplication, changes in gene regulatory systems, transposition of genes, horizontal gene transfer, etc. (2) Natural selection is for saving advantageous mutations and eliminating harmful mutations. Selective advantage of the mutation is determined by the type of DNA change, and therefore natural selection is an evolutionary process initiated by mutation.
That claim differentiates ridiculous theories from my model of biophysically constrained biologically-based cause and effect. The differences were noted in 1991 when Roger Penrose wrote:
How often do we still hear that quantum effects can have little relevance in the study of biology, or even that we eat food in order to gain energy? – From What is Life? (reprint edition)
See also: The Latest Discovery In Quantum Physics Shows Reality Is Not What It Seems
New experiments and studies conducted in laboratories such as CERN seem to suggest that everything is actually composed of energy rather than material particles, including human beings.