Achiral GnRH: no prophesy, just prediction

Predictions build on facts, mysterious “tongues” do not. (1 Corinthians 14:2-4)

Effective communication demands that audiences understand what serious scientists and theologians can or cannot predict. Predicting the end of evolutionary theory or the end of the world by focusing on a model of biological facts may be an important aspect of effective communication. A problem may be the words and phrases that pseudoscientists and serious scientists use. Some make biological facts seem like mysteries until the facts are effectively communicated. The solution should be simple. See for example: The Scent of Eros: Mysteries of Odor in Human Sexuality.

Our book received positive reviews based on my co-author’s ability to avoid the jargon typically used by scientists, including me. Helen Fisher, who effectively communicates her perspectives on anthropology, wrote this about our book: “This is science at its best, with adventure, ideas, and lots of facts… You will never look at your lover or your family the same way again.” Her review and reviews by several others suggested to me that the late Robert T. Francoeur, had helped us make the importance of odors clear to those who are not familiar with the jargon of neuroscientists.

However, in the context of what they call “nutriepigenomics” researchers recently reported that  “…γ-aminobutyric acid, serotonin, catecholamines and acetylcholine may modulate neural signaling within the enteric nervous system, when released in the intestinal lumen, and, consequently, brain function [72].” If they thought that meant anything to researchers outside the confines of their specific discipline(s), they could have addressed the molecular mechanisms that link nutrient-uptake to RNA-mediated events and amino acid substitutions that differentiate all cell types in all organisms of all species via the conserved molecular mechanisms of nutrient-dependent pheromone-controlled reproduction. See for comparison, “…noradrenergic, dopaminergic, serotoninergic, and opiotergic pathways; inhibitory neurotransmitters (e.g., gammaaminobutyric acid) and excitatory amino acids (e.g., glutamic and aspartic acids); and other brain peptides including pineal secretions (melatonin) and corticotropinreleasing hormone, and the complex interactions among them are subtle but functional species-specific influences on the electrochemical transmission of neuronal signals that the hypothalamus translates to the chemical signal GnRH (Grumbach & Styne, 1992, p. 1164).


GnRH chemical structure — achiral glycine amino acid substitution at position 6

See also: Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor

“…a single substitution of the chiral amino acid in position 6 of GnRH in jawless fish by the achiral glycine facilitated formation of a type II’ β-turn conformation of GnRH to allow close spatial interaction of these two functional elements.”
“…the surprising total conservation of GnRH II’s primary structure, from bony fish to man, appears to be a result of the excellent coordinated evolutionary selection of amino acids participating in binding, activation and configuration such that its structure cannot be improved by substitution with any natural amino acid at any position.”

Apparently, some theorists and theologians think that proteins evolve. That is why they may not understand the link from food odors and pheromones to the chemical signal GnRH (gonadotropin releasing hormone). Proteins… consisting of one or more long chains of amino acid residues differ from one another primarily in their sequence of amino acids, which is dictated by the nucleotide sequence of their genes, and which usually results in folding of the protein into a specific three-dimensional structure that determines its activity. If you think that any specific three-dimensional structure evolves, you may not know about biophysical constraints on protein folding. The constraints prevent folding dysfuntional proteins like those associated with mutations, which perturb protein folding.

Jordan et al., (2005) claimed: “We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms.”

Theorists and theologians who think that proteins evolved may never realize the need to link ecological variation to ecological adaptations in all species. Why isn’t it obvious to them that before the last universal common ancestor of all extant organisms somehow emerged, it already had some form of nutrient-dependent metabolism that linked its epigenetic landscape to the amino acid substitutions of its proteome?

In all vertebrates, for example, GnRH is the link from nutritional epigenetics to the diversity of their proteomes, which is manifested in their morphological and behavioral phenotypes. Evolutionary theorists may continue to tout theories that link mutations and/or natural selection to the evolution of biodiversity manifested in morphological phenotypes. Indeed, most evolutionary theorists seem to think they need to learn nothing about ecology because their theories explain all that their target audience needs to know. In some cases, they may think their target audiences prefer not to learn what is known about epigenetic links between morphological phenotypes and behavioral phenotypes.

Special Issue “Nutritional Epigenetics”

Publication of: Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors (2012) and Nutrient-dependent/pheromone-controlled adaptive evolution: a model (2013) led Dr. Justin O’Sullivan, one of two guest editors of the special issue linked above, to request a submission from me that addressed what was currently known about nutritional epigenetics. If he has asked for a submission on “nutriepigenomics,” which is a portmanteau of nutritional epigenetics, I would have requested that he attempt to communicate more effectively. Instead, I submitted a manuscript about nutritional epigenetics on March 19, 2014, which was promptly rejected on April 10, 2014 with this comment:

“… we have decided to reject your paper nutrients-53064. During the peer review process, we had invited a lot of referees but most of them declined, only one reject report was received stating: Comments and Suggestions for Authors: This is unfocussed and self-aggrandizing.

The series of accepted and published works in the special issue linked above fails to incorporate any model that links nutrient-dependent RNA-directed DNA methylation to RNA-mediated events and cell type differentiation controlled by the metabolism of nutrients to species-specific pheromones. That means the special issue of the journal will be of little help to anyone who needs to link genetic networks and metabolic networks to health and disease via the conserved molecular epigenetics of cell type differentiation we first detailed in our 1996 Hormones and Behavior review article (e.g., in the section on molecular epigenetics). See: From Fertilization to Adult Sexual Behavior

“Molecular epigenetics
Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.”

Would reviewers at Nutrients also think that statement was unfocussed?  If so, how much of what is currently known cannot be considered by researchers who have focused on one relatively small part of how genetic networks and metabolic networks are linked to cell type differentiation in species from microbes to man? See for comparison: Alternative RNA Splicing in Evolution “…alternative splicing may be the critical source of evolutionary changes differentiating primates and humans from other creatures such as worms and flies with a similar number of genes.” Worms Caenorhabditis elegans. Flies = Drosophila melanogaster. I reiterate, we wrote: “That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.” Clearly, we are now among others who understand that similarities in the molecular epigenetics of cell type differentiation via alternative splicings of pre-mRNA and RNA-mediated amino acid substitutions may be important to consider in the context of ecological speciation compared to the inexplicable evolution of biodiversity.

Since then, Nutrient-dependent/pheromone-controlled adaptive evolution: a model (2013) was reviewed in Criticisms of the nutrient-dependent pheromone-controlled evolutionary model,

Andrew Jones claimed “…James V. Kohl overextends his expertise in trying to overthrow established evolutionary theory.” I expected my conclusion to make it clear that I was presenting facts about how nutrient-dependent amino acid substitutions differentiate the cell types of all individuals of all species. Based on acceptance of our 1996 model, and my other published works, I wrote: “Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.” For comparison, the book: Mutation-Driven Evolution was published on the same day as my model. The author Masatoshi Nei concluded: “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements.”

For contrast, Role of olfaction in Octopus vulgaris reproduction, cites Kohl (2013) in this context:

Excerpt 1) “…the stimulation of the olfactory lobes with 17ß-oestradiol increased the Oct-GnRH mRNA confirming the existence of a strong coupling between 17ß-oestradiol and the transcriptional activity of Oct-GnRH neurons.

Excerpt 2) “Future work on O. vulgaris olfaction must also consider how animals acquire the odours detected by the olfactory organ and what kind of odour the olfactory organ perceives. The OL acting as control centre may be target organ for metabolic hormones such as leptin like and insulin like peptides, and olfactory organ could exert regulatory action on the OL via epigenetic effects of nutrients and pheromones on gene expression (Kohl, 2013; Elekonich and Robinson, 2000).”

Excerpt 3) “the olfactory lobe of O. vulgaris could represent the on–off switch between food intake and reproduction.”

Clearly a model that links food intake to reproduction is important to compare to a model of mutation-driven evolution, which is what Andrew Jones could have done in Criticisms of the nutrient-dependent pheromone-controlled evolutionary model,. Instead, what we now have is another RNA-mediated link between microbes and man, which helps to establish facts associated with the conserved molecular mechanisms of cell type differentiation.

Pre-mRNA-mediated cell type differentiation in From Fertilization to Adult Sexual Behavior was extended to Organizational and activational effects of hormones on insect behavior. That model led from Honey bees as a model for understanding mechanisms of life history transitions to GnRH-modulated morphological and behavioral phenotypes of cephalopods via conserved molecular mechanisms. Yet, without effective communication from serious scientists, pseudoscientists may make the facts detailed via use of model organisms appear to be less believable than their ridiculous theories about the evolution of biodiversity. Pseudoscientists may also claim that presentations of biological facts are unfocussed and self-aggrandizing, especially if they have learned to accept only the ridiculous claims of theorists without ever comparing them to a model of biological facts.

See:  Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems or this 5.5 minute video representation of biologically-based cause and effect.

Abstract: 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.


“Biological Laws

Biophysical constraints and biological laws appear to link ecological variation to ecological adaptations via conserved molecular mechanisms in all species. For example, nutrient-dependent ecological niche construction leads to pheromone-controlled social niche construction via the nutrient-dependent pheromone-controlled physiology of reproduction. The nutrient-dependent origin of amino acid substitutions in viruses [153-156], which also are manifested in plant and animal interactions, exemplifies a continuum of biological plausibility and ecological validity in the context of Laws of Biology. These Laws of Biology include Kohl’s Laws of Biology, which are so-named because the surname of the first author or sole author on each of 7 peer-reviewed publications in the paragraph below is Kohl. The Kohls did not create the Laws of Biology; they merely independently incorporated what is known about them into what appears to be a cohesive series of published works.

Kohl’s [self-aggrandizing] Laws of Biology

Life is nutrient-dependent. That is a Biological Law. The ecological origin of all biological laws is apparent 1) in the context of systems biology [91]; 2) in the context of the metabolism of nutrients by microbes [157]; and 3) in the context of how the metabolism of nutrients results in species-specific pheromones that control the physiology of reproduction [158]. Taken together, the systems biology of nutrient metabolism to species-specific pheromones, which control the physiology of reproduction, can be expressed in a summary of Kohl’s Laws of Biology: 1) Life is nutrient-dependent. See for review [2, 31]. The physiology of reproduction is pheromone-controlled. See for review [30]. In the context of nutrient-dependent epigenetically-effected human reproduction, it is clearer that the epigenetic effects of human pheromones integrate neuroendocrinology and behavior [104], which includes the neuroendocrinology of mammalian behavior associated with the development of sexual preferences [159].”

Kohl’s Laws help to explain what was missing from Darwin’s ‘conditions of life.’ Darwin knew nothing about genetics, which means he knew nothing about the epigenetic effects of food odors or pheromones.

Anyone who wonders why they might need to link genetic networks and metabolic networks to health and disease via the conserved molecular epigenetics of cell type differentiation we first detailed in our 1996 Hormones and Behavior review article (e.g., in the section on molecular epigenetics) may want to see this 2-minute long video from the Mayo Clinic about medications and prevention of side-effect. The testing currently available links genetic networks to metabolic networks and it will probably become part of standard medical practice if physicians are willing to add to their responsibilities.

My comment: See also:Clinically Actionable Genotypes Among 10,000 Patients With Preemptive Pharmacogenomic Testing

Other blog posts on this site that address the future of evolutionary theory compared to facts about biologically-based cause and effect include:

Neo-Darwinism is Dead: Long live Darwin’s ‘conditions of life’

Genome Dynamics Events: the end of evolutionary events

Svante Paabo et al: the end of evolutionary theory

Evolutionary heritage or ecological adaptation? Racism versus reality

Quantum biology

The quantum biology of consciousness

Forces of “Nature” limit dissemination of information

Evolving DNA before RNA

Something from no thing

Quantum consciousness: seeing the light


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