Documenting the epigenetic landscape of human innate immune cells reveals pathways essential for training macrophages.
September 25, 2014 [open access]
Excerpt: “...they then analyzed genome-wide distributions of four epigenetic indicators of gene activity: DNAse hypersensitivity and three different histone modifications—trimethylation of histone H3 at lysine 4, monomethylation of histone H3 at lysine 4, and acetylation of histone H3 at lysine 27. They also analyzed genome-wide transcription and transcription factor binding.
Together the analyses pointed to specific genes and pathways that defined the four cell types, as well as the genes’ surrounding regulatory regions. Of particular interest was the discovery that genes associated with signaling via cyclic adenosine monophasphate (cAMP)—a molecule regulating cell metabolism, among other processes—and glycolysis—a pathway that produces energy from glucose—were specifically activated in the trained macrophages.
The team went on to show that these two pathways were necessary for developing the trained phenotype.”
My comment: Three large teams collectively linked nutrient-dependent RNA-directed DNA methlylation from biophysically constrained ecological adaptations to the development of morphological phenotypes and the concurrent development of behavioral phenotypes.
1) The thermodynamics of protein biosynthesis and degradation and organism-level thermoregulation links ecological variation from nutrient-dependent gycolysis to experience-dependent RNA-mediated de novo Creation of odor receptor genes.
2) Food odors induce the de novo Creation of odor receptor genes. Odors can then classically-condition receptor-mediated behaviors that are directly linked to choices associated with nutrient uptake.
3) Receptor-mediated behaviors link nutrient uptake to the metabolic shift (see below), which links the metabolism of nutrients to species-specific pheromones.
4) Pheromones control the physiology of reproduction.
5) Nutrient-dependent pheromone-controlled reproduction enables fixation of RNA-mediated amino acid substitutions that stabilize methylated DNA in the organized genomes of species from microbes to man.
6) Pheromones classically condition differences in nutrient-dependent behaviors that lead to successful nutrient-dependent reproduction via amino acid substitutions that stabilize organism-level thermoregulation.
7) The nutrient-dependent pheromone-controlled stability of organism-level thermoregulation is perturbed by nutrient stress and social stress.
8) Organisms with the greatest DNA stability are ecologically adapted.
9) Nutrient-dependent pheromone-controlled organized genomes are morphologically and behavioral adapted to the ecological variations they are most likely to encounter.
From Science Magazine:
Metabolic shift may train immune cells [subscription required]
Received: Thu, 25 Sep 2014 22:56:29 -0400
My comment: Kondrashov (2012) linked nutrient-dependent gene duplication from ecological variation to ecological adaptations in yeast via the yeast hexose transporter and the rate of glucose transport into the cell. “One of the main duplicated gene families are the olfactory receptor proteins [18,117–119] so perhaps their duplication may lead to an increase in sensitivity to a particular odour may be adaptive under certain conditions.” https://rspb.royalsocietypublishing.org/content/early/2012/09/05/rspb.2012.1108.abstract
We linked the metabolism of nutrients to species-specific pheromones and sex difference in cell types via RNA-mediated events. https://www.ncbi.nlm.nih.gov/pubmed/9047261
Others have since linked nutrient-dependent pheromone-controlled differences in cell types to hormone-organized and hormone-activated behaviors. https://www.ncbi.nlm.nih.gov/pubmed/10980296
Thus, the ability of yeasts to recognize RNA-mediated sex differences in cell types appears to extend across species to recognition of nutrient-dependent glycolysis-induced learning and memory in the context of immune system recognition of cell type differences and gene duplication associated with pheromones that control the physiology of reproduction in species from microbes to man.
That link from the epigenetic landscape to the physical landscape of DNA in organized genomes is exemplified in the honeybee model organism.
“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, and diseases of the X chromosome (Honeybee Genome Sequencing Consortium, 2006). Included among these different aspects of eusocial species survival are learning and memory, as well as conditioned responses to sensory stimuli (Maleszka, 2008; Menzel, 1983).” https://www.socioaffectiveneuroscipsychol.net/index.php/snp/article/view/17338
This report seem to clarify several aspects of how glycolysis is linked from nutrient uptake to cell type differentiation and ecological speciation. Biodiversity is associated with RNA-mediated amino acid substitutions and recognition of cell type differences by conspecifics and heterospecifics due to differences in their diet, glycolysis, and the pheromones they produce.
My comments on the most recent attempt to keep the focus on evolution via definitions with no experimental evidence of biologically-based cause and effect is here: