“The gene, cell, tissue, organ, organ-system pathway is a neuroscientifically established link between sensory input and behavior. Marts and Resnick (2007) stress the importance of this pathway in the context of a systems biology approach to pharmacogenomics.” (Kohl, 2012)

“Naftolin (1981) stressed its importance to the understanding of sex differences. This pathway is sensitive to conditioning. Sensory input from an organism’s environment activates and reactivates the pathway and causes changes in hormone secretion that condition hormone-driven behavior.” (Kohl, 2012)

See the full tutorial on Pharmacogenomics here

Nutrient-dependent RNA-directed DNA methylation links altenative splicings of pre-mRNA from ecological variation to ecological adaptations in species from microbes to man via conserved molecular mechanisms. See Diamond, Binstock, and Kohl (1996), especially our section on Molecular epigenetics. Our focus was on the gonadotropin releasing hormone (GnRH) neuronal system of mammals because it links what is known about sex differences in cell type differentiation from yeasts to primates. However, the molecular epigenetics of cell type differentiation link genetic networks and metabolic networks to all cell type differences in all individuals of all organisms.

See also: Prenatal Ethanol Exposure Disrupts Intraneocortical Circuitry, Cortical Gene Expression, and Behavior in a Mouse Model of FASD

“Changes in gene expression reported in this study may be caused by altered DNA methylation, an epigenetic modification that cells use to mediate gene expression (Moore et al., 2013), cell differentiation, and embryonic development (Monk et al., 1987; Feng and Fan, 2009)…. Methyltransferase activity can be modified by exposure to ethanol; chronic exposure to ethanol is associated with reduced DNMT3B mRNA expression and hypermethylation in adults (Bönsch et al., 2006). Embryonic exposure to ethanol has been shown to alter DNA methylation patterns at neurulation, with increased methylation of genes on chromosome 10 and X correlating with an increase in neural tube defects (Liu et al., 2009). Furthermore, ethanol exposure impacts methyl donors (Mason and Choi, 2005), highlighting a possible mechanism by which ethanol, through methylation, can drive downstream epigenetic modifications and alter gene expression, as we have seen in this study (Haycock, 2009).”

Epigenetic effects of food odors and social odors called pheromones link the alpha mating pheromone of yeasts to the human response to ethanol exposure. The yeasts produce ethanol and ethanol alters the GnRH-directed luteinizing hormone (LH) response to in adult humans. The GnRH-directed LH response also links epigenetic effects of food odors and human pheromones on GnRH and its downstream effects on other hormones that affect behavior during its development. For example, a single nutrient-dependent amino acid substitution associated with exposure to food odors links the systems complexity of behavioral development to differences in adolescent and adult human behavior via cell type differentiation. See: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults.

The link from food odors and nutrient uptake to an amino acid substitution and life history transitions in humans can now be compared to the life history transitions during the development of honeybees. The transitions effectively link epigenetic effects on all other model organism to humans, which means they can be considered in the context of amino acid substitutions linked to morphological and behavioral phenotypes via genetic networks and metabolic networks. Genetic and metabolic networks drive all biological processes. You can think of them as bridges between the organism and the individual molecules – proteins and genes – that form all living cells.

The extent of these bridges in other organisms was detailed in Nutrient-dependent/pheromone-controlled adaptive evolution: a model.The availabilty of genetic testing that links genetic networks and metabolic networks via RNA-mediated events and amino acid substitutions that differentiate cell types heralds the next generation of personalized medicine in which practitioners can learn more about how to prevent reactions to medications and how to ensure the right dose is presecribed on the basis of individual differences in cell types that are manifested in links between genes, metabolism, and behavior.

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