Nutrient–dependent / Pheromone–controlled Adaptive Evolution: A Model

Kohl, J.V. (accepted) Nutrient–dependent / Pheromone–controlled Adaptive Evolution: A Model. Socioaffective Neuroscience & Psychology.

Abstract:

Background: The prenatal migration of gonadotropin releasing hormone (GnRH) neurosecretory neurons allows nutrients and human pheromones to alter GnRH pulsatility, which modulates the concurrent maturation of the neuroendocrine, reproductive, and central nervous systems, thus influencing the development of ingestive behavior, reproductive sexual behavior, and other behaviors.

Methods: This model details how chemical ecology drives adaptive evolution via 1) ecological niche construction, 2) social niche construction, 3) neurogenic niche construction, and 4) socio-cognitive niche construction. The model exemplifies the epigenetic effects of olfactory/pheromonal conditioning, which alters genetically predisposed, nutrient–dependent, hormone–driven mammalian behavior and choices for pheromones that control reproduction via their effects on luteinizing hormone (LH) and systems biology.

Results: Nutrients are metabolized to pheromones that condition behavior in the same way that food odors condition behavior associated with food preferences. The epigenetic effects of olfactory/pheromonal input calibrate and standardize molecular mechanisms for genetically predisposed receptor–mediated changes in intracellular signaling and stochastic gene expression in GnRH neurosecretory neurons of brain tissue. For example: glucose and pheromones alter the hypothalamic secretion of GnRH and LH. A form of GnRH  associated with sexual orientation in yeasts links control of the feedback loops and developmental processes required for nutrient acquisition, movement, reproduction, and the diversification of species from microbes to man.

Conclusion: An environmental drive evolved from that of nutrient ingestion in unicellular organisms to that of pheromone–controlled socialization in insects. In mammals, food odors and pheromones cause changes in hormones such as LH, which has developmental affects on pheromone–controlled sexual behavior in nutrient–dependent reproductively fit individuals across species of vertebrates.

Refutations in review:

REFUTATION: I wrote: “Evidence from genome wide analysis suggests that polymorphisms cause alterations in neural connections and signaling in olfactory pathways, which contribute to natural variation in olfactory perception in flies (Swarup, Huang, Mackay, & Anholt, 2013).” That evidence links olfactory/pheromonal input to genetically predisposed species-specific behavior via previously unmodeled epistatic interactions that must occur throughout the lifecycle transitions of all organisms. Adaptive evolution cannot occur without epigenetically altered nucleotide sequences, which enable the de novo protein biosynthesis that is required.

REFUTATION: Axelsson et al’s study (2013) was cited in the context of Lord (2013) which enabled the comparisons made.

REFUTATION:  I am confused by the comments and mention of DNA mutations, which my model clarifies are actually epigenetically effected changes due to dietary differences that cause changes in the pheromones and behavior of species from honeybees to mammals, like dogs and wolves via diet-driven changes in nucleotide sequences, not via random mutations. I wrote: “Compared to any theory of mutation–caused adaptive evolution, however, the difference in this link from olfactory/pheromonal input to genetically predisposed memory via protein biosynthesis includes the molecular mechanisms that link epigenetic effects on genes to behavior and back via learning and memory.”

REFUTATION:  I wrote: “Pheromones are… substances which are secreted to the outside by an individual and received by a second individual of the same species, in which they release a specific reaction, for example, a definite behavior, or a developmental process (Karlson & Luscher, 1959, p. 55).” This reviewer muddies the water by insisting on use of “(i.e., a clearly identified compound (or mixture of some compounds in given ratio secreted de novo and inducing, in conspecifics, clear behavioral or neuroendocrine responses which expression is not context-dependent and independent of induction by previous exposure or learning effects)…” in the definition. I addressed this obfuscation: in the context of Richard Doty’s book “The Great Pheromone Myth” in which he argues there are no mammalian pheromones, and thus there can be no human pheromones, which is only true if you redefine the term, as this reviewer now suggests I should do.

REFUTATION: The demonstration of cause and effect in every species – to include details from the human literature – is deliberately avoided. The purpose of the model is to show that the molecular mechanisms are the same, which means they extend across species to humans, whether or not this can be proved in the most highly adapted species of all.

REFUTATION: The proximate cause of oxytocin release has not been detailed. The reviewer seems willing to accept the link to meaningful interpretations from brain imagery, even though there exists no known proximate mechanism that links ecological and social niche construction to oxytocin release sans conditioning by olfactory/pheromonal input.

REFUTATION: e = an effect on hormones. a = an affect on behavior. Affects on behavior do not occur without effects on hormones. I use the correct terms consistently. They are not interchangeable!

REFUTATION: The title is: Nutrient–dependent  / Pheromone–controlled  Adaptive Evolution: A Model. All models are speculative. Recent works have extended the concept of nutrient-dependent single nucleotide polymorphisms and amino acid substitutions to include their effect on thermoregulation associated with pheromone production and sexual selection in mice and in a human population that appears to have adaptively evolved during the past ~30,000 years (Grossman et al., 2013; Kamberov et al., 2013).

REFUTATION: In the key to Figure 1, I wrote: The genetically predisposed embryonic migration of GnRH neurons to the hypothalamus… Migration occurs from the olfactory placode, which links migration to the olfactory bulb and thereby to the sense of smell. The respected neuroanatomist Simon Le Vay acknowledges this in the context of a previously published 57-page book chapter in the Handbook of the Evolution of Human Sexuality.

p. 210 This model is attractive in that it solves the “binding problem” of sexual attraction. By that I mean the problem of why all the different features of men or women (visual appearance and feel of face, body, and genitals; voice quality, smell; personality and behavior, etc.) attract people as a more or less coherent package representing one sex, rather than as an arbitrary collage of male and female characteristics. If all these characteristics come to be attractive because they were experienced in association with a male- or female-specific pheromone, then they will naturally go together even in the absence of complex genetically coded instructions.” (LeVay, 2011)

p. 210 – 211 “Still, even in fruit flies, other sensory input besides pheromones — acoustic, tactile, and visual stimuli — play a role in sexual attraction, and sex specific responses to these stimuli appear to be innate rather than learned by association [36.]. We simply don’t know where the boundary between prespecified attraction and learned association lie in our own species, nor do we have compelling evidence for the primacy of one sense over another.”(LeVay, 2011)

Note: when a neuroanatomist insists on using insects without indicating what differences there might be in the olfactory systems, I should not be held accountable for not detailing the neuroanatomical differences across species. I am instead showing that the molecular mechanisms are the same. The primacy of olfaction is established via these molecular mechanisms, which is what I have detailed for inclusion in my model.

REFUTATION: There is an obvious need for study of many different nutrients and their epigenetic effects in different species. Before proceeding to detail the epigenetic requirements for Darwin’s “Conditions of Existence” in different species, I have chosen to detail the model that establishes the fact that these conditions of existence are nutrient-dependent and pheromone-controlled. In subsequent publications I will address the role of docosahaexonoic acid (DHA) in human myelination et al., and the epigenetic effects of other nutrients: citrate uptake in Escherichia coli. Extant literature now includes “Food as a hormone” by Ryan and Seely (2013) published in “Science” on 2/22/13, which was after I submitted this paper for review. Additional delays in publication may cause my paper to become less relevant given the accumulation of evidence in just the past 2.5 months.

REFUTATION:  I do not know what the reviewer is saying is wrong. It may be that it is not well known that pheromones are like food odors in the role they play in classical/Pavolovian/respondent conditioning, which are all the same:  From Wikipedia: Classical conditioning (also Pavlovian conditioning or respondent conditioning) is a form of learning in which the conditioned stimulus or CS, comes to signal the occurrence of a second stimulus, the unconditioned stimulus or US. (A stimulus is a factor that causes a response in an organism.) The conditioned response is the learned response to the previously neutral stimulus (e.g., the food odor or the pheromones).

REFUTATION: There are no citations that support direct epigenetic effects of visual or auditory stimuli on gene expression in hormone-secreting nerve cells of brain tissue. The epigenetic effects are invariably associated with olfactory/pheromonal conditioning, which is the central theme of my model. The link from the sensory environment to changes in hormones that affect behavior is a general rule in the context of hormone-organized and hormone-activated behavior. Many people simply ignore the fact that no direct link from visual or auditory stimuli to genes and behavior and back has ever been detailed. Or, they simply assume cause and effect has been established, when it has not been. That’s why I wrote: “behavior is caused by unknown epigenetic effects of visual or auditory stimuli on gene expression…” Clearly, cause is unknown although visual and auditory stimuli are errantly considered primary.

REFUTATION I wrote: “…alterations occur during synaptogenesis, synaptolysis, and apoptosis that cause changes in neurotransmission…” which uses the concept of synaptolisis (sp?) in the context of neurotransmission. I do not know how to make the concept of synaptolysis more clear. If synapses are lysed (i.e., destroyed) neurotransmission changes as it does with synaptogenesis and cell death (i.e., apoptosis).

Citations:

Grossman, Sharon R., Andersen, Kristian G., Shlyakhter, I., Tabrizi, S., Winnicki, S., Yen, A., et al. (2013). Identifying Recent Adaptations in Large-Scale Genomic Data. Cell, 152(4), 703-713.

Kamberov, Yana G., Wang, S., Tan, J., Gerbault, P., Wark, A., Tan, L., et al. (2013). Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant. Cell, 152(4), 691-702.

Karlson, P., & Luscher, M. (1959). Pheromones: a new term for a class of biologically active substances. Nature, 183(4653), 55-56.

LeVay, S. (2011). Gay, Straight, and the Reason Why: The Science of Sexual Orientation: Oxford University Press.

Swarup, S., Huang, W., Mackay, T. F. C., & Anholt, R. R. H. (2013). Analysis of natural variation reveals neurogenetic networks for Drosophila olfactory behavior. Proc Natl Acad Sci U S A, 110(3), 1017-1022.