Epigenetic pharmacology and RNA-mediated transciptional landscapes

Last year, Vosshall’s group eliminated ideas about the involvement of beneficial mutations in the nutrient-dependent cell type differentiation of mosquitoes. orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET. This year her group showed that nutrient-dependent amino acid substitutions clearly are involved in cell type differentiation. Evolution of mosquito preference for humans linked to an odorant receptor

RNA-mediated events have since been linked to sexual dimorphism in mosquitoes. Examination of the genetic basis for sexual dimorphism in the Aedes aegypti (dengue vector mosquito) pupal brain

Excerpt: “Transcripts (2,527), many of which were linked to proteolysis, the proteasome, metabolism, catabolic, and biosynthetic processes, ion transport, cell growth, and proliferation, were found to be differentially expressed in A. aegypti female vs. male pupal heads.”

My comment: The authors address the complexity of cell type differentiation in the context of sex differences. Nutrient-dependent RNA-mediated events, which are linked from the de novo creation of olfactory receptor genes in mosquitoes, can now be linked via their pheromone-controlled physiology of reproduction via RNA-mediated events that link morphological and behavioral diversity in species from microbes to man via conserved molecular mechanisms.

The idea that cell type differentiation could arise via mutations and natural selection or somehow evolve has been subjected to scrutiny by serious scientists for more than 18 years. For example, we started from sex differences in cell types of yeasts, worms, and flies. “Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation…”  Our model of nutrient-dependent RNA-mediated cell type differentiation and pheromone-controlled reproduction was extended to insects and subsequently to the life history transitions of the honeybee model organism.

No matter how many times I have mentioned these facts, or included comments that the same model applies to differences of cell types that vary with sexual orientation, other researchers have consistently focused on attempts to find genes that can somehow be linked to cell type differentiation. They have ignored the fact that “…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).”

They have ignored thermodynamic cycles of protein biosynthesis and degradation that lead from glucose uptake to pheromone-controlled cell type differentiation via RNA-mediated events in all species, from yeasts to other mammals via amino acid substitutions.

Gene duplication as a mechanism of genomic adaptation to a changing environment

Comparison of the transcriptional landscapes between human and mouse tissues

For the role of amino acid substitutions in comparisons of the transcriptional landscapes between human and mouse tissues see Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

Excerpt: “High excretion rates of trimethylamine-associated odor in humans cause ‘fish odor syndrome’. The aversive body odor has been attributed to a mutation (Dolphin, Janmohamed, Smith, Shephard, & Phillips, 1997). This attribution is not consistent with the portrayal of synergy in the mouse model, which enables both the production of the odor and the response to the odor.

This synergy requires at least two things to happen simultaneously: for example, (1) natural selection for nutrient chemicals and (2) sexual selection for odor production. Sexual selection for nutrient-dependent odor production is not likely to be achieved via one mutation involved in nutrient acquisition and another mutation that is involved in odor production because two mutations are not likely to simultaneously occur.”

My comment: Clear links from genetic networks to metabolic networks have been used to develop pharmacogenomic profiles that predict how patients with different genotypes will manifest differences in their phenoytpes via examples of enymatically metabolized therapeutic drugs that link RNA-mediated amino acid substitutions to tissue-specific differences in cell types and behavior.

Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing

Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults

Cell Context Dependent p53 Genome-Wide Binding Patterns and Enrichment at Repeats

An integrative analysis of DNA methylation and RNA-Seq data for human heart, kidney and liver

circRNA Biogenesis Competes with Pre-mRNA Splicing

Excerpt: “…canonical pre-mRNA splicing can compete with circularization of exons. Mechanisms of this competition are tissue specific and conserved from flies to humans.

Evolutionary biologists, human ethologists, and other social scientists continue to claim that mutations somehow lead to the evolution of biodiversity when no experimental evidence of biologically-based cause and effect suggests that is possible. I reiterate: “Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation…” — and to cell type differentiation of all cells in all individuals of all species. If not for the ridiculous claims of pseudoscientists, serious scientists might have convinced everyone to quit funding the pseudoscientific nonsense of evolutionary theory. Instead, works are funded that have no benefit whatsoever, while those that link the epigenetic landscape to the physical landscape of DNA in the organized genomes of microbes to man fall short of what would otherwise be remarkable progress.


About James V. Kohl 1307 Articles
James Vaughn Kohl was the first to accurately conceptualize human pheromones, and began presenting his findings to the scientific community in 1992. He continues to present to, and publish for, diverse scientific and lay audiences, while constantly monitoring the scientific presses for new information that is relevant to the development of his initial and ongoing conceptualization of human pheromones. Recently, Kohl integrated scientific evidence that pinpoints the evolved neurophysiological mechanism that links olfactory/pheromonal input to genes in hormone-secreting cells of tissue in a specific area of the brain that is primarily involved in the sensory integration of olfactory and visual input, and in the development of human sexual preferences. His award-winning 2007 article/book chapter on multisensory integration: The Mind’s Eyes: Human pheromones, neuroscience, and male sexual preferences followed an award winning 2001 publication: Human pheromones: integrating neuroendocrinology and ethology, which was coauthored by disinguished researchers from Vienna. Rarely do researchers win awards in multiple disciplines, but Kohl’s 2001 award was for neuroscience, and his 2007 “Reiss Theory” award was for social science. Kohl has worked as a medical laboratory scientist since 1974, and he has devoted more than twenty-five years to researching the relationship between the sense of smell and the development of human sexual preferences. Unlike many researchers who work with non-human subjects, medical laboratory scientists use the latest technology from many scientific disciplines to perform a variety of specialized diagnostic medical testing on people. James V. Kohl is certified with: * American Society for Clinical Pathology * American Medical Technologists James V. Kohl is a member of: * Society for Neuroscience * Society for Behavioral Neuroendocrinology * Association for Chemoreception Sciences * Society for the Scientific Study of Sexuality * International Society for Human Ethology * American Society for Clinical Laboratory Science * Mensa, the international high IQ society