Biophysically constrained nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation link the epigenetic landscape to the physical landscape of DNA in all living genera.
Genomic stability arises in the context of a fine-tuned balance of viral microRNAs and nutrient-dependent microRNAs. RNA-mediated gene duplication and RNA-mediated amino acid substitutions stabilize organized genomes.
Nutrient-dependent microRNAs are linked by RNA-mediated amino acid substitutions from ecological variation to protection from DNA damage caused by viral microRNAs. The microRNA/messenger RNA balance links ecological variation to ecological adaptations in individuals and species that survive via the nutrient-dependent physiology of reproduction in all living genera. This model links nature to nurture via the epigenetic effects of stress on nutrient-dependent cell type differentiation.
Nature: The genetically predisposed embryonic migration of GnRH neurons to the hypothalamus is controlled by in utero nutrient stress and social stress (see Fig. 1). Stress alters fine-tuning, which is required for the homeostasis that supports the optimal epistatic outcome of gestation.
Nurture: Genetic predispositions, nutrient stress, and social stress continue to impact prenatal and postnatal development of the brain during sexual differentiation (Makris et al., 2013). Food odors and sex differences in the effects of pheromones on neurosecretory neurons in brain tissue of the hypothalamus alter postnatal brain development via their epigenetic effects on GnRH pulse frequency.
The mammalian model was developed in the 80’s. In the early 1990’s, I discussed it with Bruce McEwen who recently published:
“…a continually changing pattern of gene expression mediated by epigenetic mechanisms involving histone modifications and CpG methylation and hydroxymethylation as well as by the activity of retrotransposons that may alter genomic stability.”
My comment: Viruses have since been linked to all pathology via perturbed protein folding. They appear to link entropic elasticity to genomic entropy, which is the opposite of genomic stability.
SRSF1 and other splicing factors can also direct a related process called alternative splicing—the mixing and matching of different exons from one gene, which, when spliced together, give rise to variant versions of a single protein, ones that often have very different functional properties.
“Long ago we and others saw that the levels of splicing proteins are altered in various cancers,” says Krainer. “Previous work indicated that there are lots of alterations in splicing in the context of cancer,” he says.
The model that Bruce McEwen claimed must start with gene activation was included in our 1996 Hormones and Behavior review of RNA-mediated cell type differentiation in the context of alternative splicings, which have repeatedly since been linked to healthy longevity or to virus-driven pathology in species from microbes to man.
For example, in their comment on Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution, the authors claim:
The major antigenic changes of the influenza virus are primarily caused by a single amino acid near the receptor binding site.
No model of biologically-based cause and effect that suggests that viruses evolve or that genomic stability “evolves.” See for comparison to McEwen et al (2015), which is a detailed model that does not mention mutations, natural selection or evolution.
Non-genetic modifications could also contribute to genomic evolution by introducing genetic variability, as they can promote DNA mutations, recombination and transposition, and alter genome stability. Their complex interplay with genetic factors may affect outbred populations; for example, domestication modifies DNA methylation and non-Mendelian patterns of inheritance90, and mate preference and natural selection are influenced transgenerationally by non-genetic marks91. The integration of non-genetic germline inheritance and molecular aspects of genetic inheritance is essential and offers a unified theory of evolution that reconciles the contribution of environmental and genetic factors in a dual neo-Lamarckian and neo-Darwinian view92.
My comment: This conclusion starts with genomic evolution, which was eliminated from consideration in McEwen et al (2015). My comment to “Science Magazine” on the misrepresentation of evolved viruses was replaced by the author’s comment sometime after it was published in the comments section in November, 2013.
Here is the comment that was initially published, but replaced.
The idea of biophysical constraints seems antithetical to the idea of nature somehow selecting mutations that cause amino acid substitutions. However, I am not a biophysicist or evolutionary theorist.
The problem may be my focus on nutrient-dependent receptor-mediated amino acid substitutions in species from bacteria to humans (non-viral organisms). Since I am not a virologist or physicist, I’m not sure that the laws of physics apply to viruses and their replication.
If they do, natural selection for random mutations is not likely to result in amino acid substitutions because the thermodynamics of changes in organism-level thermoregulation preclude such randomness. Stability of protein biosynthesis and degradation that probably depends on protein folding must somehow be controlled. Besides, I don’t know how random mutations in viruses could be naturally selected for inclusion in the human virome (or in the virome of any organism capable of thermoregulating its thermodynamic intercellular signaling).
If the Second Law of Thermodynamics does not apply to viruses, which means the chemical bonds that enable the amino acid substitutions can form at random and somehow be naturally selected, the details of biophysical constraints in this article seems out of place, since I do not think in terms of constrained random mutations and natural selection in mutation-driven evolution.
Hopefully, someone with a background in biophysics will address my confusion in case others are confused. In addition, I wonder if the consequences of understanding the evolutionary mechanisms that govern viruses extend to consequences important to understanding the evolution of species from bacteria to humans via constrained random mutations and natural selection?
Obviously, the authors capitulated after I called their attention to what was an obvious mistake. Science Magazine delivered what should have been a correction to a gross misrepresentation of biologically-based cause and effect.The amino acid substitutions linked to the seasonal need to be vaccinated for influenza are nutrient-dependent. The nutrients are stolen from the cells that the viruses enter because the nutrients allow the viruses to replicate and adapt to changes in host’s immune system.
Until biologically-based cause and effect is differentiated from evolution, the difference between biophysically constrained nutrient-dependent protein folding and the initial representation that viruses “evolve”can still be linked to the evolution of something else: virulence and pathology.
…although human A/H3N2 seasonal influenza viruses have fixed amino acid substitutions at 54 positions in antigenic sites, substitutions at only seven of these locations have been responsible for the major antigenic changes in these viruses to date. Moreover, these locations are all near the RBS of the HA, which suggests the mechanism for slowing the antigenic evolution of these viruses could be a reduction in receptor binding function. This small number of critical positions, and the restricted amino acid usage involved in antigenic cluster transitions, suggests that possibilities for important antigenic change of seasonal influenza viruses may be more restricted than previously thought, with potentially far-reaching consequences for understanding the underlying evolutionary mechanisms governing such viruses.
These authors did not support their ridiculous misrepresentation of “…the underlying evolutionary mechanisms governing such viruses.” The underlying mechanisms of virus-driven pathology are nutrient-dependent and controlled only by nutrient-dependent RNA-mediated gene duplication and RNA-mediated amino acid substitutions that differentiate the cell types of all individuals of all living genera. Cell type differentiation in living genera typically prevents virus-driven pathology.
There is no
unified theory of evolution that reconciles the contribution of environmental and genetic factors in a dual neo-Lamarckian and neo-Darwinian view
The neo-Darwinian view was based on the assumptions of population geneticists and de Vries 1904 definition of “mutation.” Evolutionary theorists decided to make claims about how long it would take for one species to accumulate enough mutations and evolve into a new species.
Theorists are already attempting to put viruses and virulence into their “tree of life” pseudoscientific nonsense.
They would not reassert their pseudoscientific nonsense if they knew anything about cell type differentiation. More than 2 decades ago, Bruce McEwen told me to “start with gene activation” or my model of biologically-based could not be validated. At that time my model for linking effects on genes to affects on behavior was incomplete.
Theorists refuse to acknowledge the fact that the model has since been validated with details of RNA-mediated protein folding biochemistry. Also, theorists still refuse to offer any model of biologically-based cause and effect for comparison.
Most theorists seem to think that ridiculous claims about Mutation-Driven Evolution can be compared to Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
The problem with their neo-Darwinian theories is their failure to learn the difference between “effect” and “affect.” Since they cannot link epigenetic effects to behavior, they keep trying to link mutations to morphological phenotypes — and to behavioral phenotypes — without telling anyone how epigenetic effects on hormones lead to affects on behavior in all vertebrates and invertebrates.
For comparison to their ridiculous diatribes, see: Correction for McEwen, 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.”
My comment: The difference between effect and affect is significant enough for an outstanding researcher like Bruce McEwen to issue a correction. His correction serves as an example of what must be learned by others who tout theories about mutations, natural selection, and the evolution of biodiversity.
Most of them think their ridiculous theories link effect to affect because they know nothing about epigenetic effects on cell type differentiation that lead to affects on behavior. Many of them think they can start with genes and automagically arrive at biodiversity without the need to learn anything about how physics, chemistry, or the conserved molecular mechanisms of biologically-based cause and effect are linked to affects on behavior.
See for example:
The researchers found no significant differences between men and women, but did find significant differences in the Level 2 details of fingerprints between people of European American and African American ancestry.
My comment: This suggests the differences attributed to ancestry can be linked via nutrient-dependent RNA-mediated amino acid substitutions that link sex differences in yeasts from chromosomal rearrangements to all cell type differences in modern human populations without the pseudoscientific nonsense about mutations, natural selection and evolution via the physiology of reproduction.
1) “It’s not quite the Holy Grail of fingerprinting, but it’s a very important discovery,” Marcel de Puit, fingerprint researcher at the Dutch Forensic Institute (NFI), told AFP on Wednesday, hailing what he said was a world’s first.2) The prints themselves are made up of sweat and grease, including a complex mix of cholesterol, amino acids and proteins.
My comment: Researchers funded in part by the NSF in China recently linked the “holy grail” of RNA-mediated protein folding to the “holy grail” of fingerprinting via amino acid substitutions. I reported that in a different blog post to this domain.
In order for a biological model to work, it needs data. In this case, the data comes from exposing a plant to stress.
…have zeroed in on a previously unknown mechanism within the cell growth cycle that controls cell size. The fundamental finding was made by studying yeast cells, but could provide insight to basic human biology as well as diseases such as cancer that thrive by manipulating this mechanism.
Our epigenetically-effected molecular “mechanisms” are conserved and they link the epigenetic landscape to the physical landscape of DNA via metabolic networks linked to genetic networks in all living genera.
When theorists try to explain how metabolic networks are linked to genetic networks in all living genera, they tend to boldly claim that mutations and natural selection can lead to evolution. The difference between a evolutionary theorist and a serious scientist is the explanatory power of the claims, which must be based on experimental evidence of biologically-based cause and effect.
Footnote 2′ Effect(s)’ and ‘affect(s)’. In context, sensory input effects hormones that affect behavior. An effect of sensory input on hormones can result in behavioral affects/affects on behavior.
My comment: A reviewer had claimed I used these words interchangeably, which required me to add the footnote to explain that I was using the terms properly in an accurate representation of what is required to link effects on hormones to affects on behavior. Theorists try to do that with claims that mutations are linked via natural selection to evolution, which is why they don’t address the evolution of sex differences in behavior, or any other aspect of “evolved” biologically-based behavior. They look at morphological traits like fingerprints, and claim the traits “evolved.”
That’s why I claim that some people are anonymous fools and/or biologically uninformed science idiots.Dobzhansky made a similar claim in: “Biology, molecular and organismic” (1964)
“The notion has gained some currency that the only worthwhile biology is molecular biology. All else is “bird watching” or “butterfly collecting.” Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists!”
…a special force or energy, which he called by the Aristotelian name “entelechy,” was active in living bodies.
See also: “Perfuming the Mind: The Biological Logic of Physical Attraction” published in “Entelechy”
My published works have focused on the anti-entropic force of nutrient-dependent energy and its epigenetic effects on hormones that affect behavior. Evolutionary theorists and most theoretical physicists have fallen more than 40 years behind what was known to Dobzhansky in 1964 and what was reported by him in 1973.
“…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)”
My comment: Biologically uninformed theorists may continue to try and put that fact and the facts about fingerprinting into the context of their ridiculous theories, but the end result will be the same. Serious scientists will continue to expose the ignorance of theorists, which is what serious scientists have always done. If phys.org did not remove all posts that moderators decide are “pseudoscience” because the links are to works by creationists, others would already have learned the difference between the non-mainstream claims of creationists and the pseudoscience of the mainstream claims by evolutionary theorists.
Do you think Dawkins knows something about biological evolution that Bruce McEwen or other serious scientists don’t know?