Dobzhansky 1973 and precision medicine

By: James V. Kohl | Published on: January 19, 2017

MicroRNA-34 directly targets pair-rule genes and cytoskeleton component in the honey bee

Our findings point to miR-34-5p as novel regulatory component in the complex molecular cascade that governs insect segmentation and to a broader role of miRNAs in the early development due to the detection of mature transcripts from both 5p and 3p arms for several precursor miRNAs. Thus, this work encourages further investigation to pinpoint miRNAs as fine tuners of insect early development.

Anna Di Cosmo‘s group took the lead and already linked all invertebrates to all vertebrates via the conserved molecular mechanisms that link microRNA flanking sequences to all energy-dependent  biophysically constrained biodiversity.

See for example: Role of olfaction in Octopus vulgaris reproduction (January 1, 2015)

For a perspective, see: The phylogenetic utility and functional constraint of microRNA flanking sequences (February 18, 2015)

The majority of flanking sequences used in our analyses are composed of non-coding intergenic DNA, suggesting that conservation of these hairpin-loop flanking sequences is independent of either the presence of exonic sequence or protein-coding gene regions.

For the extension to humans, see:

Practical Approaches for Whole-Genome Sequence Analysis of Heart- and Blood-Related Traits

 …all amino acid substitutions or all promotor variants are not equal, and one can predict the impact based on knowledge of the location and type of substitution.

All cell type specific and tissue type specific amino acid substitutions in all individuals of all living genera are energy-dependent and biophysically constrained by the physiology of pheromone-controlled reproduction. A long-time antagonist echoed that fact in the human ethology yahoo group, but he took facts about complex traits out of context. See: Practical application of whole-genome sequencing

The complex traits used here are heart and blood related ones, but the concepts are applicable to all complex genetically-sourced traits, including behavioral ones. — Clarence A. ‘Sonny’ Williams

Complex traits are not genetically sourced. The physiology of pheromone-controlled reproduction is clearly the link to the complexity of all nutrient energy-dependent morphological and behavioral traits.
See: No Genetics without Epigenetics? No Biology without Systems Biology?

…a unified understanding of life requires: (1) a view on its component parts, the cells, (2) a view on the life cycles of all cells—their formation, growth, development, and reproduction—as based in chemical reactions among similar sorts of molecules, (3) a view on the way in which amino acids are put together to form proteins, as specified by DNA and RNA according to a nearly universal and precise scheme.

That fact makes it perfectly clear that behavioral traits are not genetically sourced. All traits arise only in the context of systems biology, which links the epigenetic landscape to the physical landscape of supercoiled DNA in all living genera. For comparison, Clarence A ‘Sonny Williams wrote:

mutations in gene regulatory regions are the “driving force” behind human brain complexity. 


I do not reply to creationists or anyone who does not believe that humans evolved via Darwinian natural selection.

The facts about systems biology were stated clearly in Dobzhansky’s Nothing in Biology Makes Any Sense Except in the Light of Evolution (1973)

Cytochrome C is an enzyme that plays an important role in the metabolism of aerobic cells. It is found in the most diverse organisms, from man to molds. E. Margoliash, W. M. Fitch, and others have compared the amino acid sequences in cytochrome C in different branches of the living world. Most significant similarities as well as differences have been brought to light. The cytochrome C of different orders of mammals and birds differ in 2 to 17 amino acids, classes of vertebrates in 7 to 38, and vertebrates and insects in 23 to 41; and animals differ from yeasts and molds in 56 to 72 amino acids. Fitch and Margoliash prefer to express their findings in what are called “minimal mutational distances.” It has been mentioned above that different amino acids are coded by different triplets of nucleotides in DNA of the genes; this code is now known.

See also:

For example, the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla.

The de novo creation of amino acids has since been linked from chirality to autophagy and healthy longevity via chromosomal rearrangements.
Light-Induced Opening and Closing of the Intramolecular Hydrogen Bond in Glyoxylic Acid
Single-residue insertion switches the quaternary structure and exciton states of cryptophyte light-harvesting proteins
Dynamic control of chirality and self-assembly of double-stranded helicates with light
The Intrinsically Disordered Protein Atg13 Mediates Supramolecular Assembly of Autophagy Initiation Complexes

The cycle of interconversion of assemblies and helicities shown here holds promise to design other dynamic systems driven out of equilibrium by light energy.

See also: ATP hydrolysis by UPF1 is required for efficient translation termination at premature stop codons
The de novo creation of amino acids has since been linked from the energy-dependent creation of helicase to the structure of functional DNA. Theories about minimal mutational distances have been replaced by facts that link angstroms to ecosystems in all living genera via biophysically constrained RNA-mediated protein folding chemistry.

See: Structural diversity of supercoiled DNA

Our data provide relative comparisons of supercoiling-dependent twisted, writhed, curved, and kinked conformations and associated base exposure. Each of these structural features may be differentially recognized by the proteins, nucleic acids, and small molecules that modulate DNA metabolic processes.

They linked energy-dependent metabolic networks to genetic networks by recapitulating Dobzhansky’s claims and in this parody they add: “every angstrom is dynamic from the 5 prime to the three”

See also: Structure of eukaryotic CMG helicase at a replication fork and implications to replisome architecture and origin initiation

…definitive conclusions about the exact role of the N-tier in helicase mechanism will require higher resolution to identify candidate-specific amino acid residues, followed by direct mutagenesis and biochemical characterization.

Although the candidate-specific amino acid residues have not been identified, the energy-dependent creation of RNA-mediated amino acid “residues” links the anti-entropic virucidal energy of sunlight from angstroms to ecosystems in all living genera via chirality and autophagy, which protect all organized genomes from virus-driven entropy in the context of the transgenerational epigenetic inheritance of all morphological and behavioral phenotypes.

See also: Codon identity regulates mRNA stability and translation efficiency during the maternal-to-zygotic transition

The amino acid optimality code (Fig 6) provides an alternative perspective on sequence changes between paralogs in evolution and human disease.

See also: Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes

The ZAL2 and ZAL2m alleles code for 597 amino acids, with two fixed differences driving a Val73Ile and Ala552Thr polymorphism in ZAL2m. valine to alanine substitution

How social learning adds up to a culture: from birdsong to human public opinion

For human online cultures, we suggest that it may be useful to consider features of birdsong learning, which have been optimized over millions of generations to give rise to stable polymorphic cultures. Experimenting with implementation of similar features in online communication systems could potentially facilitate the design of more stable and balanced information systems, which can potentially promote distributed self-governance.

Public opinion (above) is based on bird-brained representations of pseudoscientific nonsense about “…balanced information systems, which can potentially promote distributed self-governance.” The information systems are not linked from energy-dependent changes in the microRNA/messenger RNA balance to all biodiversity via the physiology of pheromone-controlled reproduction. Instead the information systems automagically may promote “distributed self-governance” across all species in the context of millions of years of evolution.

In my model of biologically-based cause and effect, top-down causation is linked from natural selection for energy-dependent codon optimality to the physiology of reproduction and all biodiversity via supercoiled DNA, which protects all organized genomes from virus-driven energy theft and genomic entropy.

For an example of medication-induced genomic entropy, see: Some Antibiotics Linked to Serious Nerve Damage

The FDA is strengthening its warning that a popular class of antibiotics, called fluoroquinolones, may cause sudden, serious, and potentially permanent nerve damage called peripheral neuropathy.

See also: There is nothing inevitable or natural about chronic disease

Causation at the molecular level, deep inside the body, appears to be beyond our current reach

See for comparison: Understanding and accounting for relational context is critical for social neuroscience

George Ellis:

This is absolutely correct and forms part of the larger concept that top-down causation is a key factor not just in the way the brain works but in broader contexts in biology and even physics. This is explored here:

I wrote:

New data on how genetic predispositions are epigenetically linked to phenotypically distinct neuroanatomy and behaviors is provided in the honeybee model. Across-species comparisons from insects to vertebrates clearly show that the epigenetic influence of food odors and pheromones continues throughout the life of organisms that collectively survive whereas individuals do not. These comparisons also attest to the relative salience of sensory input from the rearing environment. For example, when viewed from the consistency of animal models and conditioned behaviors, food odors are obviously more important to food selection than is our visual perception of food. Animal models affirm that food odor makes food either appealing or unappealing. Animal models reaffirm that it is the pheromones of other animals that makes them either appealing or unappealing.

Socioaffective neuroscience and psychology may progress more quickly by keeping these apparent facts in mind: Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans (Keller et al., 2007; Kohl, 2007; Villarreal, 2009; Vosshall, Wong, & Axel, 2000).” — Kohl, JV (2012) Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors
See also: Methylation Maestro

So are many others who do not understand how energy-dependent changes in chirality must be linked from autophagy to supercoiled DNA in the context of the physiology of reproduction and fixation of RNA-mediated amino acid substitutions.

They have failed to link the National Microbiome Initiative to the Precision Medicine Initiative via RNA-mediated protein folding chemistry and are trapped in theories with no explanatory power.

If you ask one of them about the virus-driven energy theft of quantized energy, which is linked to all pathology, they will run away. They cannot stand to think about how the potential of hydrogen (pH) must be linked from sunlight to all biodiversity via the claims of Schrodinger in What is Life? (1944)

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