For presentation during session: Polycomb and chromatin remodeling

Historical perspective:

Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes… Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans…. 1

MicroRNA is the term now used for pre-mRNA and there are nearly 109,000 indexed publications that mention microRNAs.The ultraviolet (UV) light-activated weekend resurrection of the bacterial flagellum 2 presciently established that energy-dependent biophysically constrained cell type differentiation occurs across kingdoms in the context of the physiology of pheromone-regulated microRNA-mediated genetic processes. Facts about the energy-dependent fixation of two amino acid substitutions in the organized genome of Psueudomonas fluourescens have since been placed into the context of the newly coined term optoribogenetics.

Initial claims about an evolutionary pathway linked to the weekend resurrection of the bacterial flagellum led to a claim that “… natural selection can rapidly rewire regulatory networks in very few, repeatable mutational steps. Both steps linked energy-dependent oxidative phosphorylation to microRNA-mediated fixation of amino acid substitutions and survival of the species.

Step 1 increased intracellular levels of phosphorylated gene, ntrC, which alters an amino acid  within the DNA binding domain. Step 2 redirected NtrC away from nitrogen uptake and toward its novel function as a flagellar regulator.

NtrB and NtrC make up a two-component system: Under nitrogen limitation, NtrB phosphorylates NtrC, which activates transcription of genes required for nitrogen uptake and metabolism.

Claims about  a two-step evolutionary pathway make no sense in the context of what is known about optoribogenetics and microRNA-mediated cause and effect.

For instance, a two component system is unlikely to evolve in the context of UV light and water-dependent oxidative phosphorylation and RNA-mediated gene activation or microRNA-mediated silencing.3 For comparison, Bazzini et al., (2016) linked natural selection for light-activated carbon fixation and food energy-dependent pheromone-regulated genetic processes of codon optimality to4 energy-dependent microRNA-mediated polycombic ecological adaptations which are manifested in the supercoiled DNA of mammals.5

Chromosomal inheritance links the ecological adaptations from morphological phenotypes to healthy longevity via behavioral phenotypes and transgenerational epigenetic inheritance across kingdoms via microRNA-mediated biophysically constrained viral latency.6

Optoribogenetic control of regulatory RNA molecules7 that sexually differentiate the cell types of individuals and species is the obvious link from alternative splicings of otherwise identical genes to microRNA-mediated energy-dependent fixation of amino acid substitutions and ecological adaptations.

See also: A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission.8 The link from two amino acid substitutions to the weekend resurrection of the bacterial flagellum and the end of transmission of the 1918 influenza can be viewed in the context of what was known about energy-dependent pheromone-regulated genetic processes of pheromone-controlled RNA-mediated cell type differentiation in 1996.1

Simply put, food energy and pheromone-controlled reproduction are required for survival of species from microbes to humans whether the term microRNA or pre-mRNA is used.


  1. Diamond, M.; Binstock, T.; Kohl, J. V., From Fertilization to Adult Sexual Behavior. Horm Behav 1996, 30 (4), 333-53.
  2. Taylor, T. B.; Mulley, G.; McGuffin, L. J.; Johnson, L. J.; Brockhurst, M. A.; Arseneault, T.; Silby, M. W.; Jackson, R. W., Evolutionary rewiring of bacterial regulatory networks. Microb Cell 2015, 2 (7), 256-258.
  3. McEwen, B. S.; Allfrey, V. G.; Mirsky, A. E., Dependence of RNA synthesis in isolated thymus nuclei on glycolysis, oxidative carbohydrate catabolism and a type of “oxidative phosphorylation”. Biochim Biophys Acta 1964, 91, 23-8.
  4. Bazzini, A. A.; Del Viso, F.; Moreno-Mateos, M. A.; Johnstone, T. G.; Vejnar, C. E.; Qin, Y.; Yao, J.; Khokha, M. K.; Giraldez, A. J., Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition. EMBO J 2016.
  5. Irobalieva, R. N.; Fogg, J. M.; Catanese, D. J.; Sutthibutpong, T.; Chen, M.; Barker, A. K.; Ludtke, S. J.; Harris, S. A.; Schmid, M. F.; Chiu, W.; Zechiedrich, L., Structural diversity of supercoiled DNA. Nat Commun 2015, 6.
  6. Barbu, M. G.; Condrat, C. E.; Thompson, D. C.; Bugnar, O. L.; Cretoiu, D.; Toader, O. D.; Suciu, N.; Voinea, S. C., MicroRNA Involvement in Signaling Pathways During Viral Infection. Frontiers in Cell and Developmental Biology 2020, 8 (143).
  7. Pilsl, S.; Morgan, C.; Choukeife, M.; Möglich, A.; Mayer, G., Optoribogenetic control of regulatory RNA molecules. Nature Communications 2020, 11 (1), 4825.
  8. Tumpey, T. M.; Maines, T. R.; Van Hoeven, N.; Glaser, L.; Solorzano, A.; Pappas, C.; Cox, N. J.; Swayne, D. E.; Palese, P.; Katz, J. M.; Garcia-Sastre, A., A two-amino acid change in the hemagglutinin of the 1918 influenza virus abolishes transmission. Science 2007, 315 (5812), 655-9.

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