Amino acid substitutions, stress, and human behavior

By: James V. Kohl | Published on: January 7, 2016

Stress dynamically regulates behavior and glutamatergic gene expression in hippocampus by opening a window of epigenetic plasticity


…33% of the human population present a BDNF Val66Met SNP that leads to a valine-to-methionine substitution in the BDNF protein at codon 66, and this SNP has been associated with increased susceptibility to development of stress-related disorders (21, 22).

Reported as: Newly discovered windows of brain plasticity may help with treatment of stress-related disorders

The researchers also identified the molecule regulating the regulator, an enzyme called P300. By adding chemical groups to proteins known as histones, which give support and structure to DNA, P300 increases expression of mGlu2, they found.

My comment:  They linked a nutrient energy-dependent base pair substitution and the BDNF Val66Met amino acid substitution from ecological variation to ecological adaptations via a metabolic networks linked to a genetic network. The conserved molecular mechanisms can be compared in the context of life history transitions that link the honeybee model organism to humans. For example, the COMT Val158Met substitution links histones to supercoiled DNA, which appears to protect the organized genomes of all living genera from virus driven entropy.
See also: Additive Gene–Environment Effects on Hippocampal Structure in Healthy Humans

Similarly, BDNF Val66Met, a single nucleotide polymorphism (SNP) located in the brain-derived neurotrophic factor gene (BDNF), has been associated with stress susceptibility (Gatt et al., 2009; Alexander et al., 2010). Further, COMT Val158Met, a functional SNP located in the catechol-O-methyltransferase gene (COMT), has been implicated in HPA axis hyper-reactivity (Armbruster et al., 2012), altered μ-opioid neurotransmitter responses to pain stressors (Zubieta et al., 2003), and increased limbic reactivity (Smolka et al., 2005).

My comment: The links from nutrient energy-dependent base pair substitutions to RNA-mediated amino acid substitution and SNPs linked to behavior are clear and the amino acid substitutions are linked to morphological and behavioral phenotypes across all genera.
See the examples in: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

The honeybee already serves as a model organism for studying human immunity, disease resistance, allergic reaction, circadian rhythms, antibiotic resistance, the development of the brain and behavior, mental health, longevity, diseases of the X chromosome, learning and memory, as well as conditioned responses to sensory stimuli (Kohl, 2012).

See also: Human pheromones: integrating neuroendocrinology and ethology

The effect of sensory input on hormones is essential to any explanation of mammalian behavior, including aspects of physical attraction. The chemical signals we send have direct and developmental effects on hormone levels in other people. Since we don t know either if, or how, visual cues might have direct and developmental effects on hormone levels in other people, the biological basis for the development of visually perceived human physical attraction is currently somewhat questionable. In contrast, the biological basis for the development of physical attraction based on chemical signals is well detailed.

My comment: Our award-winning 2001 review has since been cited in these recently published works, which link atoms to ecosystems via the model of nutrient-dependent receptor-mediated events and examples of RNA-mediated amino acid substitutions.
See: Investigating biomolecular recognition at the cell surface using atomic force microscopy

The fission yeast pheromone receptor is a kind of G protein-coupled receptor (GPCR), a typical membrane receptor protein on cell surface. These receptors are activated by pheromone binding and then enable cellular signal transduction (Kohl et al., 2001).

See also: Chemosignals from isolated females have antimutagenic effect in dividing the cells of bone marrow from male mice of the CBA strain

See also: Coding of Group Odor in the Subcaudal Gland Secretion of the European Badger Meles meles: Chemical Composition and Pouch Microbiota

Abstract excerpt:

As it is likely that the variation in metabolic activity is found at the species-, subspecies-, or even strain-level, future high-throughput sequencing can be expected to reveal more subtle differences in the microbial communities between social groups.


Some Actinobacteria have been found to play a major role in the transformation of odorless steroids into odorous derivatives (e.g., Gower et al. 1986 , Kohl et al. 2001 ).

We wrote:

The odors produced by humans are a function of the location on the body where the odor is being produced. The amount of available oxygen as well as water and skin gland secretions determine the type and number of cutaneous flora, which are present on different body areas. Moist areas of the body, such as the mouth, axillae, genital region, and feet, support greater varieties and numbers of bacteria because they are occluded, or are moist because of their function (e.g., mouth, vaginal barrel). The type and density of cutaneous microorganisms on different areas of the body interacting with skin and other glandular secretions give rise to a variety of odors from various body sites.

Citations by others
My comment: The links from the skin microbiome to individual-specific and species-specific pheromones have since been widely reported as have links from the gut microbiome. Every aspect of pheromone production links metabolic networks to genetic networks via the conserved molecular mechanisms detailed in the molecular epigenetics section of our 1996 Hormones and Behavior review. From Fertilization to Adult Sexual Behavior


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