Alternative pre-mRNA splicing and ecological adaptation

By: James V. Kohl | Published on: September 20, 2015

This startup thinks it can speed up a cure for cancer by bringing scientific research into the YouTube era
Excerpt:

The current scholarly publishing model did not allow me to present the research I was doing. I created [Figshare] initially out of purely selfish reasons and I spent my evenings and weekends creating a platform that allowed me show, in a super simple way, data sets, and videos to put me ahead of the rest of my peers.

I’ve used his platform, and recommend it for that purpose. See also:

The 2013 video representation of my model of nutrient-dependent thermodynamic cycles of protein biosynthesis and degradation, which control biodiversity via the physiology of reproduction is linked on figshare.com to the poster presentation and the presentation text.
Publication of the model as Nutrient-dependent/pheromone-controlled adaptive evolution: a model put me ahead of my peers and publication led to a request for an invited review of nutritional epigenetics, which I also posted to figshare.com
See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
Abstract:

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.

My comment: I posted the text of the invited review to figshare because my submission was returned without review, albeit with one comment. Supposedly, my invited review was self-aggrandizing.
I suspect that comment came from someone who was embarrassed by their ignorance. Ignorance of biologically-based cause and effect is common among evolutionary theorists. Many of them do not seem to think that they must include the Laws of Physics and what is known about RNA-mediated protein folding chemistry in their representations of how mutations and natural selection link food to evolution.
For theorists, there are no Laws of Biology. For science journalist, Carl Zimmer, there also is only lawless evolution.
See:  Inuit Study Adds Twist to Omega-3 Fatty Acids’ Health Story
Excerpt 1)

Food is a powerful force in evolution.

Excerpt 2)

Natural selection is the only known way this gene variant could have become so common in the Inuit.

My comment: Carl Zimmer linked food to natural selection and evolution with no consideration for RNA-mediated gene duplication and fixation of RNA-mediated amino acid substitutions, which determine the cell types of all individuals of all living genera.
The only thing missing is a theoretical link from mutations to natural selection and evolution. No. I’m just kidding about the missing link.
Excerpt 3)

…natural selection may well favor those of us with genetic mutations that help us thrive on it.

My comment: The missing link may be whatever is favored that helps us thrive, or it may be a gene.
Excerpt 4)

As that gene spread through the Inuit population, the FADS variant might simply have been passed down with it.

My comment: Zimmer’s  simple-minded representation of a gene variant that spread through the Inuit population without mention of the fact that the nutrient-dependent pheromone-controlled physiology of reproduction is RNA-mediated allows Carl — and others like him — to continue touting their pseudoscientific neo-Darwinian nonsense about mutations, natural selection, and evolution.
In that context, mutations linked to cancer are beneficial because they are selected against to help ensure survival of the species, which is automagically the result of evolution.
See for comparison: WEBINAR: Linking Viral Discovery with Causality
Excerpt:

The majority of emerging diseases are infections with viruses that jump species barriers from wildlife or domestic animals to humans. The advent of molecular methods like high-throughput sequencing dramatically scaled viral discovery in humans and animals. Efficient and (nearly) unbiased discovery has expanded our understanding of the complexity of viral families, can inform individualized medicine, can quickly identify emerging disease, and even potentially can anticipate emergence. Many of these novel viruses are innocuous, so along with powerful discovery tools comes a responsibility in the medical research community to uncover viral pathogenesis and to clearly define associations, if present, with disease.

My comment: This will help others link the “Tree of Life” nonsense to death and disease. If you are not yet brain dead, watch the webinar and/or tell others about it. Until then, we have award-winning science journalists like Carl Zimmer to thank for the failure to find a cure for cancer and all other virus-driven pathologies (i.e., all pathologies).
Fortunately, their ridiculous misrepresentations of biologically-based cause and effect were placed back into the context of what serious scientists have confirmed about how nutrient-dependent RNA-mediated cell type differentiation occurs.
See: Structure of a yeast spliceosome at 3.6-angstrom resolution
Excerpt:

The final refined atomic model of the yeast spliceosome contains 10,574 amino acids from 37 proteins, three snRNA molecules, and an intron lariat (Fig. 3B and tables S1 and S2), with a combined molecular mass of ~1.3 MD. Among the modeled amino acids, 9312 were assigned specific side chains, and the remaining 1262 residues were built into a poly(Ala) model. U2, U5, and U6 snRNAs contain a total of 405 nucleotides, of which 314 were tentatively assigned in our atomic model.

Conclusion:

Apparently, through evolution, two highly divergent strategies have been adopted for assembling RNPs to achieve complex functions in gene expression.

My comment: These researchers automagically placed their findings on two highly divergent strategies into the context of neo-Darwinian theories about the evolution of increasingly complex gene expression and biodiversity via mutations and natural selection.
However, in a companion paper, they revealed the facts about nutrient-dependent RNA-mediated cell type differentiation and links from atoms to ecosystems via alternative splicings in the context of the structural basis of pre-mRNA.
See: Structural basis of pre-mRNA splicing
Excerpt 1)

Pre-mRNA splicing occurs through two steps, which are both SN2-type transesterification reactions (2, 3).

Excerpt 2)

Although the nature of the two-step reaction has been clearly defined for decades, how the spliceosome facilitates such reaction remains largely enigmatic. How are the reacting pieces placed into close proximity of one another in the correct temporal order?

My comment: You cannot tread lightly into the complexity that links atoms to ecosystems. In any case,  you may also quickly realize that you cannot continue to tread water and wait for someone else to link the sun’s biological energy on contact with water to all of life’s biodiversity.
Excerpt 3)
Structural determination of the yeast spliceosome at 3.6 Å resolution represents a major step forward for mechanistic understanding of the spliceosomal function. Spliceosome is a protein-controlled ribozyme.
My comment: All aspects of structural determination in species from microbes to humans are nutrient-dependent.
Their conclusion (with my emphasis):

Such a design likely optimizes the possibilities of regulation on the catalytic center and the splicing reaction. The collective action of the numerous protein components serves to deliver the critical pieces—5′SS, BPS, 3′SS, and 5′-exon—into the close proximity of the catalytic Mg2+ ions for catalysis.

My comment: The design links everything currently known to serious scientists about biophysically constrained nutrient-dependent RNA-mediated gene duplication and RNA-mediated cell type differentiation via amino acid substitutions that differentiate the cell types of all cells in all individuals of all species. The optimal design of splicing and its nutrient-dependent regulation links it to the physiology of reproduction in all living genera without any pseudoscientific nonsense about evolution.
Indeed, it seems likely that in the absence of virus-perturbed protein folding, we would all live forever. That likelihood should have forced intelligent discussion to occur about the origins of viruses before creationists took advantage of the most parsimonious explanation.
See: Viral Genome Junk Is Bunk
Excerpt:

Perhaps the evolutionists have placed the cart before the horse on this issue, as proposed by several creationist scientists.4,6 In fact, in an ironic twist, the evidence mentioned above indicates that viruses likely arose from their hosts and not the other way around. As molecular biologist and biochemist Peter Borger notes, “The most parsimonious answer is: the RNA viruses got their genes from their hosts.”

For comparison, see Excerpt 5)

…the protein components of the spliceosome are obviously indispensable for pre-mRNA splicing to proceed because, for example, defective splicing due to a mutated RNA sequence can be rescued by mutations in Prp8 from Saccharomyces cerevisiae…

Cell type differentiation in Saccharomyces cerevisiae is nutrient-dependent and pheromone-controlled.
See: From Fertilization to Adult Sexual Behavior
We linked RNA-mediated cell type differentiation from alternative splicings of pre-mRNA to sexual differentiation of cell types in species from yeasts to flies and nematodes. Others have since linked sex differences in cell types to all cell type differentition via the conserved molecular mechaisms we detailed.
Excerpt:

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.

9/18/15 Can Your Sense of Smell Predict When You’ll Die? (nematodes)

9/18/15 Scientists identify gene that triggers neural remodeling during C. elegans development (nematodes)

9/18/1558,046 fruit flies shed light on century-old biological question (flies)

7/28/12 Fruit fly with the wings of beauty
Excerpt:

When threatened, the fly flashes its wings to give the appearance of ants walking back and forth.

My comment: Does anyone think this is an example of an evolved wing appearance? How many years would it take to evolve via accumulated mutations?

9/10/15 Protein aggregation after heat shock is an organized, reversible cellular response (yeasts)

9/13/15 Nucleic acids: Stability of DNA/RNA (all living genera)

See also: Translation in action! This animation shows how mRNA is translated into an amino acid chain that becomes a protein.

My conclusion: PROTEINS AND PEOPLE DO NOT EVOLVE!

See also: Major Evolutionary Blunders: Evolutionary Predictions Fail the Reality Test

Unless you instantly reject any creationist literature for fear it might challenge your belief in pseudoscientific nonsense, you will find this statement:

When the sequence of these homeoboxes were examined in detail, the similarities among species were astounding. Over the 60 amino acids of the homeodomain, some mice and frog proteins were identical to the fly sequences at up to 59 out of 60 positions.

My comment: If he was not still dead, all serious scientists could look Theodosius Dobzhansky in the eye and tell him “You were right about one thing.”  In 1973, he wrote:

…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 (p. 127).

Obviously, he was right about the role that RNA-mediated amino acid substitutions play in the differentiation of all cell types in all individuals of all species. However he was wrong to claim that:

Evolution is God’s, or Nature’s, method of Creation. Creation is not an event that happened in 4004 B.C.; it is a process that began some 10 billion years ago and is still under way.

No experimental evidence of biologically-based cause and effect suggests that evolution can be linked to anything that began some 10 billion years ago, and nearly all experimental evidence of virus-perturbed protein folding linked to pathology suggests no species mutates and evolves via natural selection.


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