RNA-mediated epigenetic modification via DNA-methylation

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I have repeatedly used the phrase “RNA-directed DNA methylation and RNA-mediated amino acid substitutions” in the context of links from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man. See for example: RNA-mediated, with links to ~200 blog posts.

In the introduction to my 2012 review I attested to the importance of the pathway that links the epigenetic landscape to pharmacogenomics.

Excerpt: “The gene, cell, tissue, organ, organ-system pathway is a neuroscientifically established link between sensory input and behavior. Marts and Resnick (2007) stress the importance of this pathway in the context of a systems biology approach to pharmacogenomics.”

My comment: Many people now seem to realize that the gene, cell, tissue, organ, organ-system pathway links metabolic networks to genetic networks via the biophysically constrained nutrient-dependent chemistry of protein folding. Mutations perturb protein folding and lead to physiopathology. Nutrient-dependent amino acid substitutions lead to the stability of DNA in organized genomes and help to protect species from accumulating deleterious mutations. The nutrients that protect individuals and species are metabolized to species-specific pheromones that control the physiology of reproduction in species from microbes to man. Amino acid substitutions are fixed in the DNA of the populations by species-specific pheromones. The abstract below attests to what has been known about the RNA-mediated cell type differentiation in species from microbes to man since 1996 when we detailed it in the molecular epigenetics section of our Hormones and Behavior review article: From Fertilization to Adult Sexual Behavior

See also:

The noncoding human genome and the future of personalised medicine

Abstract: Non-coding cis-regulatory sequences act as the ‘eyes’ of the genome and their role is to perceive, organise and relay cellular communication information to RNA polymerase II at gene promoters. The evolution of these sequences, that include enhancers, silencers, insulators and promoters, has progressed in multicellular organisms to the extent that cis-regulatory sequences make up as much as 10% of the human genome. Parallel evidence suggests that 75% of polymorphisms associated with heritable disease occur within predicted cis-regulatory sequences that effectively alter the ‘perception’ of cis-regulatory sequences or render them blind to cell communication cues. Cis-regulatory sequences also act as major functional targets of epigenetic modification thus representing an important conduit through which changes in DNA-methylation affects disease susceptibility. The objectives of the current review are (1) to describe what has been learned about identifying and characterising cis-regulatory sequences since the sequencing of the human genome; (2) to discuss their role in interpreting cell signalling pathways pathways; and (3) outline how this role may be altered by polymorphisms and epigenetic changes. We argue that the importance of the cis-regulatory genome for the interpretation of cellular communication pathways cannot be overstated and understanding its role in health and disease will be critical for the future development of personalised medicine.

My comment: If not for the pseudoscientific nonsense touted by theoretical physicists and evolutionary theorists, the life saving information about RNA-mediated cell type differentiation that is now being presented in the context of personalized medicine could have prevented the suffering and deaths of millions during the past two decades. Nevertheless, most theorists continue to ignore the established links from physics and chemistry to the conserved molecular epigenetics of RNA-mediated cell type differentiation.

They are still touting pseudoscientific nonsense and will continue to do so until the public outcry is deafening.  The ‘eyes’ of the genome mentioned above were placed into the context of my award-winning review: The Mind’s Eyes: Human Pheromones, Neuroscience, and Male Sexual Preferences, which extended what was know about RNA-mediated cell type differences in sexual orientation, after the award winning review Human pheromones: integrating neuroendocrinology and ethology linked the 1996 model of RNA-mediated cell type differentiation to all aspects of animal behavior. Nevertheless, most people have been taught to believe in evolution but to not believe that human pheromones do not exist. The fact that human pheromones obviously exist and that pheromones control the nutrient-dependent physiology of reproduction in species from microbes to man leaves no room for ridiculous theories about the evolution of molecules or the evolution of people.

Nutrient-dependent/pheromone-controlled adaptive evolution: a model is a theory killer. Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems buries the theories of physicists and evolutionists in experimental evidence. The experimental evidence of biologically-based cause and effect that links the sun’s biological energy to the biophysically constrained chemistry of nutrient-dependent RNA-mediated events should have eliminated the need for Combating Evolution to Fight Disease.

A social insect fertility signal is dependent on chemical context

Evolution of herbivory in Drosophilidae linked to loss of behaviors, antennal responses, odorant receptors, and ancestral diet

Genetic transformation of structural and functional circuitry rewires the Drosophila brain

Vitamin A supplements, routine immunization, and the subsequent risk of Plasmodium infection among children under 5 years in sub-Saharan Africa

Adaptation on a genomic scale

collectively attest to the likelihood that theorists will never stop unless people stop listening to their pseudoscientific nonsense.

Sulfur-cycling fossil bacteria from the 1.8-Ga Duck Creek Formation provide promising evidence of evolution’s null hypothesis  was reported as: Scientists discover organism that hasn’t evolved in more than 2 billion years.

Excerpt: “The greatest absence of evolution ever reported has been discovered by an international group of scientists: a type of deep-sea microorganism that appears not to have evolved over more than 2 billion years. But the researchers say that the organisms’ lack of evolution actually supports Charles Darwin’s theory of evolution.”

My comment: Even the lack of evidence across what theorists claim is 2 billion years will not change their ridiculous beliefs. The lack of evidence will not make them learn about how ecological variation is linked from atoms to ecosystems to ecological adaptions via the de novo creation of receptors that allow nutrients to enter cells. They may never learn anything about how nutrients are metabolized to the species-specific pheromones that control the biodiversity manifested in the morphological and behavioral phenotypes of all species. Instead, they may continue to believe that “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world.” (p 199). — Mutation-Driven Evolution

See also: Methylomic trajectories across human fetal brain development

Excerpt: Our data indicate that epigenetic changes during human brain development are highly dynamic, sometimes sex-specific, and may provide clues to the origins of common neurodevelopmental disorders.

That fact can be viewed in the context of everything currently known about nutrigenomics and pharmacogenomics in the context of personalized medicine that links metabolic networks to genetic networks via this study of a 10,000 patient cohort. Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing

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