Natural variants or disease-causing mutations: Molecular signatures

Molecular signatures of G-protein-coupled receptors

  • A. J. Venkatakrishnan et al, Nature 494, 185–194 (14 February 2013)

Excerpt with my emphasis: “In this context, large international consortia that exploit next-generation sequencing technology such as the ‘1000 genome’ and ‘cancer genome’ projects are identifying natural variants and discovering disease-causing mutations.

In my model of nutrient-dependent pheromone-controlled adaptive evolution via ecological, social, neurogenic, and socio-cognitive niche construction, it is essential to distinguish between epigenetic effects of the sensory environment that cause natural variants and those associated with disease-causing mutations. Natural variants are typically adaptive. Disease causing mutations are not. Receptor-mediated epigenetic effects may cause adaptations or disease associated mutations.

See for concision: A Glimpse Inside the Control Centers of Cell Communication

Excerpt: “Receptors are complex biomolecules composed of proteins that are embedded in the outer shell of a cell — the cell membrane. These consist of thousands of atoms and have a defined spatial structure that determines their function. As the effective control centres of cell communication, they recognise stimuli or messenger substances that bind to the cell from outside and change the receptors to transmit the information about the incoming signals into the interior of the cell.”

My comment: Olfactory receptors respond to olfactory/pheromonal input with changes in their structure that enable molecules to enter nerve cells where functional changes in intracellular signaling occur. The functional changes lead to histone modifications of chromatin. This effectively enables the odor “landscape” to become the experience-dependent physical “landscape” of DNA (genes).

Natural variations in genes are experience-dependent, which means that gene activation in nerve cells that secrete gonadotropin releasing hormone (GnRH) from the medial preoptic area of tissue in the mammalian brain directly links odor-associated changes in genes to downstream effects on GnRH. The hormone, GnRH, controls the maturation of the reproductive system, the neuroendocrine system and the central nervous system of mammals. Simply put, GnRH is responsible for development of the mammalian brain and behavior.

The pathway from gene activation by odors in GnRH neurosecretory neurons to production of luteinizing hormone (LH) and follicle stimulating hormone (FSH), is essential to development of behavior. The LH/FSH ratio is a modulator of sex steroid hormone secretion and sex differences in pheromone production cause sex differences in the development of the brain and behavior.

The sex difference in pheromone production alter GnRH and sex differences in its downstream effects on sex differences in behavior. The effect of the pheromones is on hormones; their affect is on behavior. Affects of hormones on behavior are associated with other sensory input but other sensory input does not directly effect GnRH secretion. (It is essential to know the difference between an effect of hormone secretion and and affect of hormones on behavior in attempts to understand behavior, because hormones organize and activate behavior in vertebrates and invertebrates. That is how hormones affect behavior.

Sensory input that does not directly effect hormone-secreting nerve cells of brain tissue, cannot directly affect behavior. That is why visual and auditory input can only indirectly affect behavior via associations with olfactory/pheromonal input. Odors associated with food directly effect hormone secretion that affects behavior. Food metabolizes to pheromones that directly effect hormone secretion that affects behavior.  Visual, auditory, and tactile input do not directly effect the hormone secretion that affects behavior associated with eating, social behavior, or sexual behavior.

Eating, social, and sexual behavior are adaptively evolved from microbes to ensure that mammals like us eat and reproduce. The amount of food we eat can cause natural variations that determine differences in individuals via the same molecular mechanisms that link food odors and pheromones to natural variations in individuals and in species from microbes to man. There is one model for that: HERE IT IS!  There is no mention of mutations in the model because food and pheromones do not cause mutations that cause adaptive evolution.  Adaptive evolution is nutrient-dependent and pheromone-controlled! Mutations in individuals are not controlled, which is why they don’t control the evolution of species.

The hormone, GnRH, has been conserved in its current form across 400 million years of vertebrate evolution. The structure has not mutated. Nutrient-dependent pheromone-controlled variations in the GnRH receptor (GnRHR) have caused its diversification across species from yeasts to mammals that enable species-specific differences in responses to pheromones, while enabling species similarities in food choice.

Changes in the available food supply cause changes in its metabolism to pheromones that cause changes in reproduction. Differences in reproduction that are caused by food availability and pheromones cause species diversification. Mutations do not cause species diversification. There is no receptor-mediated way for mutations to do that.

Thus, I will reiterate what the article on G-protein-coupled receptors tells us: “In this context, large international consortia that exploit next-generation sequencing technology such as the ‘1000 genome’ and ‘cancer genome’ projects are identifying natural variants and discovering disease-causing mutations. It is now more important than ever to acknowledge that natural variations associated with nutrient stress (too much or too little food) and that natural variations associated with social stress can lead to natural variations in disease processes that are experience-dependent. We know we should avoid excess food or excess social stress for that reason. We cannot, however, avoid disease-causing mutations, which is why they are the common cause of diseases not caused by our inability to manage natural variants.

When you see and hear researchers report on variants, mutations, adaptive mutations, or adaptations due to variations, try to understand their confusion. They have not been taught anything about a model for adaptive evolution, and may not be able to understand evolution outside the context of the theory they were taught about.  It may take another decade or more for researchers to be taught or re-taught how adaptive evolution occurs, which is nutrient-dependent and pheromone-controlled.





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