Understanding of epigenetics / Overturning conventional wisdom

By: James V. Kohl | Published on: January 20, 2014

Genetic Engineering & Biotechnology News Jan 15, 2014 (Vol. 34, No. 2)

Understanding of Epigenetics Deepens

Researchers are clarifying epigenetic intricacies such as missing heritability, disease markers, methylated proteins, and imprinted genes.

  • Richard A. Stein, M.D., Ph.D.

Excerpt 1: “Several years ago, using the agouti viable yellow mouse model, Dr. Jirtle and colleagues showed that maternal nutrition modulates DNA methylation and shapes the phenotype of the offspring, opening the era of environmental epigenomics.”
“Nutritional influences will probably alter the epigenome and the phenotype in humans, too, but one should not extrapolate from mice to humans, because the imprintome varies greatly across species, and even if imprinted genes were the same between two species, they can still be regulated differently,” cautions Dr. Jirtle.”
My comment: The extrapolation from mice to humans is perfectly clear in my model of nutrient-dependent pheromone controlled ecological adaptations.
Excerpt from Kohl (2013):
“Two additional recent reports link substitution of the amino acid alanine for the amino acid valine (Grossman et al., 2013) to nutrient-dependent pheromone-controlled adaptive evolution. The alanine substitution for valine does not appear to be under any selection pressure in mice. The cause-and-effect relationship was established in mice by comparing the effects of the alanine, which is under selection pressure in humans, via its substitution for valine in mice (Kamberov et al., 2013).
These two reports (Grossman et al., 2013; Kamberov et al., 2013) tell a new short story of adaptive evolution. The story begins with what was probably a nutrient-dependent variant allele that arose in central China approximately 30,000 years ago. The effect of the allele is adaptive and it is manifested in the context of an effect on sweat, skin, hair, and teeth. In other mammals, like the mouse, the effect on sweat, skin, hair, and teeth is due to an epigenetic effect of nutrients on hormones responsible for the tweaking of immense gene networks that metabolize nutrients to pheromones. The pheromones control the nutrient-dependent hormone-dependent organization and activation of reproductive sexual behavior in mammals such as mice and humans, but also in invertebrates as previously indicated. That means the adaptive evolution of the human population, which is detailed in these two reports, is also likely to be nutrient-dependent and pheromone-controlled, since there is no other model for that.”
———————–
If Jirtle or anyone else is not comfortable with these extrapolations from mice to humans, they should explain why. Are the conserved molecular mechanisms of nutrient-dependent pheromone-controlled ecological adaptations not the same in all mammals; in all vertebrates; in all invertebrates; in all species from microbes to man? If not, what do we known about the differences?  This question arises: Does Jirtle or anyone else still think that human pheromones do not regulate the systems biology of epistasis in the human genome via precisely the same molecular mechanisms that regulate epistasis in the mouse genome and the genome of every other species on the planet.
Excerpt 2: By focusing on six autoimmune conditions, Dr. Scacheri and colleagues revealed that several SNPs in a given cell type map to multiple enhancer elements, cooperatively influencing gene expression in a model that they named the “multiple enhancer variant hypothesis.”
My comment: Given the link between olfaction, nutrient uptake, self vs non-self recognition, and the pheromone-controlled physiology of reproduction, the “multiple enhancer variant hypothesis” appears to have remarkable parallels with the ecological variants in my model of nutrient-dependent pheromone-controlled adaptation. It seems unlikely to me that any of the multiple enhancer variants would not be linked to nutrients, which would lead to the extrapolations from mice to humans in my model.
Excerpt 3: “The most acute need, at this time, is to develop such an epigenetic clock in a mouse model, to help us understand what biological processes are measured by this clock,” concludes Dr. Horvath.
My comment: Jirtle tell us to not extrapolate from mice to humans. Why does Horvath want to develop a mouse model? Will he be integrating Scacheri’s “multiple enhancer variant hypothesis”?
In the “Epigenetics: A TimeLine” inset from this article, there is no mention of our 1996 review article from which the section on molecular epigenetics was across species was extended to invertebrates  in 2000 and to their hormone-organized hormone-activated life history transitions in 2005.  It’s as if others mentioned here think these published works are of no significance when they predicted findings in DNA methylation dynamics, metabolic fluxes, gene splicing, and alternative phenotypes in honey beesEpigenomics and the concept of degeneracy in biological systems; and in Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes. 
Simply put, our 1996 review was the first attempt to overturn conventional wisdom and include molecular epigenetics in what is now referred to as a “Systems Biology” approach to understanding species diversity.
See also:

Overturning Conventional Wisdom

Genomics Sheds More Light on Journey from Early Ancestors to Modern Humans

  • Henry Gee, Ph.D.

Excerpt: “When evolution came along, a misreading of natural selection as a kind of progressive force for improvement (the result of a bastard fusion of Darwinism with older currents of thought) gave us a single line of ancestors which were presumably there in the rocks for us to find, if we knew where to look, whose evolution would naturally lead to our current exalted state, higher than apes, but beneath the angels.
The current evidence, from fossils and lately from DNA, reveals a very different picture.”
My comment: As indicated above, mutation-driven evolution via mutation-initiated natural selection is a bastardization of Darwin’s theory. It ignores Darwin’s ‘conditions of life’ which are clearly nutrient-dependent.  As we’ve seen in Understanding of Epigenetics Deepens, some of today’s top scientists have not realized that Darwin’s ‘conditions of life’ are pheromone-controlled because pheromones control the physiology of nutrient-dependent reproduction. Clearly, the bastardization of Darwin’s theory is responsible for Jirtle’s “DO NOT EXTRAPOLATE”  directive, and for Scacheri’s “multiple enhancer variant hypothesis” which extends the concept of ecological variations in the availability of food  from Horvath’s  epigenetic clock in a mouse model to nutrient-dependent pheromone-controlled ecological adaptations during the development of the human brain and behavior. Sadly, even those who seem to think that our understanding of epigenetics has deepened to not understand that molecular epigenetics is not something that should be viewed in the context of species by species examples of cause and effect.  Molecular epigenetics has been “Biological Law” since 1996.


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