MicroRNAs and the exposome

By: James V. Kohl | Published on: May 5, 2015

 MicroRNAs as Potential Signatures of Environmental Exposure or Effect: A Systematic Review


Researchers are currently publishing extensive lists of miRNAs that are responsive to environmental exposures and showing their utility as biomarkers of effect. Future research should focus on identifying the molecular mechanism behind miRNA expression changes in response to exposure to determine whether the changes in miRNA expression are merely a symptom of the (patho)physiological processes the organism undergoes after exposure, or whether miRNAs are the drivers responsible for these changes. Izzotti and Pulliero (2014) recently reviewed the putative mechanisms of action behind miRNAs’ response to environmental exposure. However, the effect of the identified miRNAs on putative mRNA targets should also be studied to determine whether the change in miRNA expression has functional consequences and which mRNAs are true miRNA targets under the given circumstances.

My comment: I’m not sure how much more research is required to show that viral microRNAs perturb protein folding and that nutrient-dependent microRNAs repair damaged DNA, which enables the link from nutrient uptake to thermodynamic cycles of protein biosynthesis and degradation via the metabolism of nutrients. The metabolism of nutrients links metabolic networks and genetic networks to the physiology of nutrient-dependent pheromone controlled RNA-mediated amino acid substitutions that are clearly linked from cell type differentiation to biodiversity.
See: Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors.
Excerpt 1)

It is now clearer how an environmental drive probably evolved from that of food ingestion in unicellular organisms to that of socialization in insects. It is also clear that, in mammals, food odors and pheromones cause changes in hormones such as LH, which has developmental affects on sexual behavior in nutrient-dependent, reproductively fit individuals across species of vertebrates.

The original environmental drive of food odors and their effect on LH shares remarkable homology with the function of a sex pheromone in yeast that links pheromones to LH and to reproductive fitness via nutrition in mammals (Maeda et al., 2010).

Excerpt 2)

…ingested plant microRNAs influence gene expression across kingdoms (Zhang et al., 2012). In mammals, this epigenetically links what mammals eat to changes in gene expression (McNulty et al., 2011) and to new genes required for the evolutionary development of the mammalian placenta (Lynch, Leclerc, May, & Wagner, 2011) and the human brain (Zhang, Landback, Vibranovski, & Long, 2011).

See also: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.


…the epigenetic ‘tweaking’ of the immense gene networks that occurs via exposure to nutrient chemicals and pheromones can now be modeled in the context of the microRNA/messenger RNA balance, receptor-mediated intracellular signaling, and the stochastic gene expression required for nutrient-dependent pheromone-controlled adaptive evolution. The role of the microRNA/messenger RNA balance (Breen, Kemena, Vlasov, Notredame, & Kondrashov, 2012; Duvarci, Nader, & LeDoux, 2008; Griggs et al., 2013; Monahan & Lomvardas, 2012) in adaptive evolution will certainly be discussed in published works that will follow.

See also: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems

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.

The idea that the conserved molecular epigenetics of RNA-mediated cell type differentiation links food odors and pheromones to biodiversity was detailed in 1996: From Fertilization to Adult Sexual Behavior. Our model of hormone-organized and hormone-activated mammalilan behavior was extended to insects in 2000 and to the life history transitions of the honeybee model organism in 2005. The model was extended to octopuses in 2015. The phylogenetic utility and functional constraint of microRNA flanking sequences links all crustaceans to all insects via the conserved molecular mechanisms of biophysically constrained microRNA balanced protein biosynthesis and degradation and amino acid substitutions that differentiate cell types.
The concept of the “exposome” was proposed in 2005: “Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology.” See also, from 2005, Feedback loops link odor and pheromone signaling with reproduction and from 2011, Frequency-Dependent Recruitment of Fast Amino Acid and Slow Neuropeptide Neurotransmitter Release Controls Gonadotropin-Releasing Hormone Neuron Excitability.
Thanks also to Rhonda Green for bringing to my attention this source for information Chapter 13: Amino Acid Neurotransmitters.
I think the late Robert L. Moss and his co-authors were the first to link a GnRH fragment consisting of the last 6 amino acids of the decapeptide to neurotransmission and to GnRH receptor-mediated behaviors that also link nutrient-dependent pheromone-controlled RNA-mediated amino acid substitutions to behavior in all vertebrates via substitution of achiral glycine in the GnRH (aka LHRH) decapeptide. See: Differential effects of a luteinizing-hormone-releasing hormone (LHRH) antagonist analogue on lordosis behavior induced by LHRH and the LHRH fragment Ac-LHRH5-10. Cited in Human pheromones: integrating neuroendocrinology and ethology

… Moss and Dudley [32] suggest that a fraction of the GnRH molecule functions directly as a neurotransmitter in rats to elicit a behavioral effect(i.e., lordosis). This behavioral effect is characteristicof a “signal” pheromone, which activates a response.

After many discussions about how the role of pheromones and GnRH were linked across species, Robert L. Moss encouraged me to write the book that was co-authored by the late Robert T. Francoeur: The Scent of Eros: Mysteries of Odor in Human Sexuality The role that human pheromones play in human sexuality has consistently been denied by many colleagues who refuse to acknowledge the difference between theories about mutations and evolution compared to facts about amino acid substitutions. The facts link ecological variation to ecological adaptations via changes in the microRNA/messenger RNA balance that link atoms to ecosystems in all genera via what is currently known about physics, chemistry, microRNAs (aka pre-mRNAs) and molecular epigenetics.

For example, the co-author of Feedback loops link odor and pheromone signaling with reproduction also co-authored Estrogen Permits Vasopressin Signaling in Preoptic Kisspeptin Neurons in the Female Mouse.

The article published last week attests to facts about amino acid-mediated regulation of GnRH neuron excitability that link vertebrate GnRH to Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes. The differences in morphological and behavioral phenotypes is clearly nutrient-dependent and pheromone-controlled, and the differences arise in the context of a difference in parental feeding.
Colleagues who have failed to link nutrient uptake from GnRH to estrogen and other hormones that affect behavior will probably continue to ignore the latest information that supports what we detailed in our 1996 Hormones and Behavior review — if only because they have failed to learn anything about cell type differentiation during the past two decades. They knew nothing about RNA-mediated sex differences in cell types in 1996 and still know nothing about RNA-mediated amino acid substitutions and cell type differentiation in 2015.

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