Mechanisms that are not understood increase clarity

By: James V. Kohl | Published on: September 12, 2014

Science 12 September 2014:
Vol. 345 no. 6202 pp. 1240-1241
DOI: 10.1126/science.1252966
  • Perspective

RNA Function

RNA and dynamic nuclear organization

  1. John Rinn1,2,3,
  2. Mitchell Guttman4

Excerpt: “While the mechanism for how lncRNAs establish these domains is not fully understood, it is becoming increasingly clear that lncRNAs are important at all levels of nuclear organization—exploiting, driving, and maintaining nuclear compartmentalization.”
My comment to Science Magazine:
Title:
RNA and dynamic nuclear organization
Received:
Fri, 12 Sep 2014 03:12:03 -0400
Your Comment:
The authors seem to link RNA-mediated events to evolutionary events that have not been described. Also, a brief look at their other works suggests there is now enough experimental evidence to support the claim that RNA-mediated events link ecological variation to nutrient-dependent ecological adaptations outside the context of evolutionary theory.
If so, Rosenberg and Queitsch (2014) may have predicted the paradigm shift in “Combating Evolution to Fight Disease.” They hinted at the likelihood that evolutionary biology might be eliminated by what has become increasingly more obvious to molecular biologists, since Dobzhansky (1973). Therefore, I repeat part of an earlier comment:
“Clearly, however, “nothing in evolution makes sense except in the light of biology” is not an exaggeration. It is a common sense statement about the biologically plausible genesis of functional cell types. Population genetics and evolutionary theories abandoned the biophysical constraints of ecological variation and the physiology of reproduction, which enable epigenetically-effected nutrient-dependent pheromone-controlled receptor-mediated ecological adaptations and species diversity via the complexities of protein folding and niche construction.”
Moving forward, if RNA-mediated events organize the cell nucleus, mutations manifested in perturbed protein folding are not likely to lead to natural selection and the evolution of biodiversity. The requirement for DNA to be found in organized genomes is biophysically constrained via the conserved molecular mechanisms of protein biosynthesis and degradation in species from microbes to man.
Instead, nutrient-dependent RNA-mediated events that appear to differentiate all cell types in all individuals of all species via amino acid substitutions link the de novo creation of new proteins to the increasing organismal complexity manifested in the morphological and behavioral phenotypes of species from microbes to man.
We can again look back on Dobzhansky (1973) and his claim that “…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.” Unless mutations also lead to cell type differentiation in different species, it’s time for all biologists to abandon evolutionary theories and accept biologically-based facts in attempts to eliminate the diseases and disorders of perturbed protein folding.
Addendum: Evolutionary theorists set the stage for misunderstanding and confusion by failing to explain how any mechanism might support their ideas about mutations and natural selection, which somehow supposedly led to the evolution of biodiversity. No evolutionary events were ever detailed in the context of biologically-based cause and effect.
Now, as co-author on this perspective, John Rinn seems to understand much more about the importance of RNA-mediated events than he did in Janurary, 2013. Back then, with co-authors he wrote: “As natural selection can only act on mutations that drive phenotypic variation…” The portrayal of the base pair change and nutrient-dependent RNA-mediated amino acid substitution in the context of some unknown evolutionary event failed to link it to the evolution of biodiversity. The result was somewhat comical. See the story-telling video. Note the confusion. What are they calling an adaptation, adaptive mutation, variant, coding mutation, and an amino acid substitution? How is it linked to evolution of the mouse or human genome via the amino acid substitution associated with the morphological differences?
The amino acid substitutions is not linked to the evolution of anything! The amino acid substitution links the epigenetic landscape to the physical landscape of DNA in the organized genomes of mice and man via RNA-mediated events, not mutations, not natural selection, and not evolutionary events.
There is no such thing as an evolutionary event! Ecological variation is epigenetically linked to ecological adaptations via nutrient-dependent pheromone-controlled cell type differentiation, which depends on RNA-mediated events and removes the pseudoscientific nonsense of mutations, natural selection, and the evolution of biodiversity from any further consideration whatsoever — unless you are a theorist. Theorists can continue their story-telling about mutations, natural selection, and the evolution of biodiversity. But if you are a serious scientist, you should laugh about those stories. I hope that John Rinn can now look back and laugh at the video, now that Genome Biology Volume 15 Issue 1 has been published. See his co-authored review:

‘Oming in on RNA–protein interactions

Excerpt: “…the interactions between pre-mRNA and proteins fine-tune alternative splicing in a manner that can gradually create new protein functionalities without the need to create additional genes and without affecting existing proteins [4-6].”
Does that sound familiar? In our 1996 Hormones and Behavior review we (TB) wrote: “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 (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.” Is anyone surprised by the likelihood that sex differences in cell types and all other cell type differentiation appears to occur via the conserved molecular mechanisms we detailed in our section on molecular epigenetics and in the rest of the review?
 


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jvkohl

https://blogs.plos.org/dnascience/2014/09/11/black-pee-disease-offers-new-view-arthritic-joints/
A frequent complaint about new editions of textbooks, such as the human anatomy and physiology textbooks I co-author, is that facts don’t change enough to warrant revision…”
RNA-mediated events change the facts about everything ever reported in the context of evolutionary biology. They link transgenerational epigenetic inheritance from ecological variation to ecological adaptations in all species.
Ricki Lewis provided an example: “My own osteoarthritis appeared at age 33, as it did in my mother and her mother.” Dr. Lewis provides additional information about biologically-based cause and effect in her review of inborn errors of metabolism that link what is now known about the metabolism of the amino acid tyrosine. “The tips of the ears may blacken. Treatment is painkillers and joint replacement surgery to allieve painful arthritis. But alkaptonuria also causes kidney stones, heart valve damage, tendon and muscle rupture, and fractures.”
Please note the link from the pigment change to other disorders is due to a genetic mutation and its transgenerational inheritance. However, the manifestations of disease processes do not show up until age 33. That fact suggests RNA-mediated events are involved in the manifestations of the metabolic disorder.
Until now, evolutionary biologists might have linked the manifestations to mutated DNA. But what is known about RNA-mediated events links the epigenetic landscape to the physical landscape of DNA in organized genomes via transgenerational epigenetic inheritance and species diversification.
Unless evolutionary biologists can explain how the mutations that lead to inborn errors of metabolism are beneficial to any population of adults, they must rewrite the textbooks that tout mutations and natural selection in the context of evolved biodiversity. Are any Inborn errors of metabolism beneficial? Until now, some evolutionary biologists seem to have accepted the ridiculous theory that mutations sometimes lead to natural selection and the evolution of biodiversity. But, biodiversity is clearly RNA-mediated in the context of the amino acid substitutions that differentiate all cell types of all individuals in all species.
The problem with the metabolism of tyrosine is an example of what can go wrong when ecological variation does not lead to ecological adaptations. It is clearly not an example of an evolutionary event that links mutations and natural selection to increasing organismal complexity.
Indeed, there is probably no such thing as an evolutionary event that can be linked to increasing organismal complexity. Only nutrient-dependent pheromone-controlled RNA-mediated events appear to do that by linking ecological variation to ecological adaptations in species from microbes to man. Thus, biological facts will force evolutionary theorists to provide an example of an evolutionary event, or to quit touting evolutionary theory as a means to somehow arrive at increased organismal complexity, which is clearly RNA-mediated by events that link ecological variation to ecological adaptations.

jvkohl

https://mbe.oxfordjournals.org/content/early/2014/09/11/molbev.msu241.full
Excerpt from their conclusion: “This finding may presage the next major research thrust in molecular evolution, namely, to apply a systems genetics perspective to the question of how genes interact with the environment and evolve toward the development of ecoresponsive phenotypes.”
Without RNA-mediated events there would be no ecoresponsive morphological or behavioral phenotypes. Nutrient-dependent pheromone-controlled RNA-mediated events link amino-acid substitutions to cell type differentiation in all cells of all individuals of all species. Why do these authors ignore what is already known about the systems genetics perspective that links the epigenetic landscape to the physical landscape of DNA in species from microbes to man via RNA-mediated events?
They seem to think that molecules ‘evolve’ and that the evolution of the molecules could lead to ecoresponsive phenotypes that are clearly nutrient-dependent. Have any molecules evolved to become a different molecule, or do biophysical constraints on thermodynamic cycles of protein biosynthesis and degradation limit ecoresponsive phenotypes to those that succeed at the organism-level of thermoregulation via RNA-mediated events?


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