Chromatin: The structure of DNA (3)
…researchers have theorized that inherited methylation, also referred to as parental imprinting, largely remains stable throughout development, except during two important developmental milestones: after fertilization and during the creation of sperm and egg cells. Altered gene imprinting at other times has been associated with developmental disorders and cancer.
My comment: Theorists have historically failed to learn or to understand anything about energy-dependent biophysically constrained RNA-mediated protein folding chemistry. They missed all paradigm shifts from the time of Einstein to the time of Schrodinger to the time of Dobzhansky, who clarified the obvious facts about how energy-dependent RNA-mediated amino acid substitutions must be linked to all biodiversity via the nutrient-dependent physiology of reproduction.
Allele-Specific Methylation, Gene Expression, and Reporter Activity
The Dlk1-Dio3 imprinted locus comprises multiple maternally expressed non-coding genes with unknown functions, including the long intergenic noncoding RNA (lincRNA) Gtl2 and large clusters of C/D box small nucleolar RNAs (snoRNAs) and microRNAs (miRNAs).
A recent report suggested that gain or loss of DNA methylation in the IG-DMR region might be regulated in a dynamic manner in the adult neurogenic niche (Ferrón et al., 2011). Consistent with this notion, we show striking cell-type-dependent variation in IG-DMR methylation in the adult brain. Furthermore, our data suggest that loss of parent-specific methylation in adult NSCs actively shapes the brain epigenome over time. Given the potential dosage effects on dozens of regulatory genes in the Dlk1-Dio3 region, this epigenetic heterogeneity may account for substantial gene expression differences during aging. Future studies combining allele-specific expression in single cells and transgenic animals will allow us to elucidate the full impact of parent-specific methylation heterogeneity on gene dosage in vivo. Our results may provide a general framework for elucidating the contribution of dynamic changes in epigenetic state to gene dosage in normal developmental context, as well as in disease. The substantial cell-to-cell epigenetic heterogeneity illustrates the limitations of bulk approaches to the study of dynamic epigenetic variations.
My comment: Simply put, they conclude that all gene-centric pseudoscientific nonsense may finally be credited for all pathology, because no consideration whatsoever was give to the role virus-driven energy theft plays in loss of function via damage to DNA. If the damage is not repaired RNA-mediated cell type differentiation cannot be linked to healthy longevity.
Healthy longevity is the only link from ecological variation to ecological adaptation in the context of the physiology of reproduction. RNA-directed DNA methylation is the energy-dependent link from variation to adaptation. For example, see: Feedback loops link odor and pheromone signaling with reproduction and see: The phylogenetic utility and functional constraint of microRNA flanking sequences.
See also: From Fertilization to Adult Sexual Behavior
In the 1950s, when the milestones of which we spoke initially were being passed, the fields of genetics and neuroendocrinology were in their infancy; the fields of immunology and olfaction/pheromone research were still in gestation. Our new insights and visions allow us to see further because we stand on the shoulders of others. And there is still much to learn. Many things we take for granted today will, no doubt, be revised or reversed tomorrow. What is known for sure, however, is that biological processes called “nature” are not simplistic. Neither is the entity called “the environment.” The two separate worlds overlap and intertwine so only a single interactive one exists. Yes, it may be simpler to look at each singly, but one does so at intellectual peril.
Clearly this paper is just an opening to consider several ideas on how biological and environmental factors might interact in shaping human sexual behavior. We hope this will both expand the search and focus it to provide greater insight. Surely the most intense scrutiny and critical analysis presently is to focus on understanding how biological factors contribute. It remains for the environmental side of the picture to be equally explored and analyzed. We see the primary contribution of this discourse, not to give answers but rather to broaden the scope of investigation. It would be helpful if some other investigators would similarly shed more light on a microanalysis of social-environmental factors impacting on sexual development.
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. The reciprocal relationships of species-typical nutrient-dependent morphological and behavioral diversity are enabled by pheromone-controlled reproduction. Ecological variations and biophysically constrained natural selection of nutrients cause the behaviors that enable ecological adaptations. Species diversity is ecologically validated proof-of-concept. Ideas from population genetics, which exclude ecological factors, are integrated with an experimental evidence-based approach that establishes what is currently known. This is known: Olfactory/pheromonal input links food odors and social odors from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man during their development.