Conclusion:
… the results here presented indicate that purifying selection is driving not only HBD evolution but also its neighbor pseudogene, HBBP1. In the light of recent advances in the characterization of the β-globin cluster, we propose that the complex patterns of diversity observed in this genomic region arose from distinct functional constraints related with the intricate process of chromatin and protein interactions coordinating the differential expression of genes at the β-globin cluster during development.
My comment: No experimental evidence of biologically-based cause and effect suggests that any locus of genes or any pseudogene has ever evolved. Purifying selection cannot drive evolution. Only energy-dependent variations can can be linked to polycombic ecological adaptation, and only virus-driven energy theft has been linked to the creation of pseudogenes in the context of biophysical constraints on viral latency.
See for comparison: microRNA Function Is Limited to Cytokine Control in the Acute Response to Virus Infection
Excerpt:
miRNA function is generally limited to cytokine levels in response to RNA viruses
Reported as: Mount Sinai Researchers Use Cellular miRNA-Elimination Tool to Study Viral Infection Dynamics
Excerpt:
…while the loss of miRNAs had a negligible impact on the cell’s immediate reaction to a virus or the short-term biology of the cell, sustained depletion had dramatic results on gene expression that was coupled to a burst of cytokines. The researchers concluded in the paper that miRNA function is limited to modulating the biology of the cell over long periods of time.
My comment: In my model, energy-dependent changes in the microRNA/messenger RNA balance link nutrient energy-dependent changes to all healthy longevity and virus-driven energy theft is linked to all pathology. Over long periods of time, autophagy is the link to polycombic ecological adaptation or virus-driven hecatombic evolution of pathology via energy-dependent biophysically constrained RNA-mediated protein folding chemistry. For example, fixation of amino acid substitutions differentiates all cell types in all individuals of all living genera in the context of the physiology of reproduction. For comparison, virus-driven hecatombic pathology is linked from mutations to all pathology.
Simply put, in my model of polycombic ecological adaptation, differential gene expression is nutrient-dependent and controlled by the physiology of reproduction.
See: Nutrient-dependent/pheromone-controlled adaptive evolution: a model
Conclusion:
…the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.
My comment: Claims about RNA-mediated polycombic ecological adaptation were first placed into the context epigenetic imprinting in our 1996 review.
See: From Fertilization to Adult Sexual Behavior
Excerpt:
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 (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). 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.
My comment: Polycombic ecological adaptation appears to link energy-dependent epigenetic effects on hormones (i.e., proteins) to chromatin structure in telomeric regions, which links the effect on transcription and silencing of various genes to hormone-organized and hormone-activated affects on behavior. The hormone-organized and hormone-activated behaviors link the epigenetic landscape of yeasts to the physical landscape of supercoiled DNA in species from bacteria to invertebrates and all vertebrates via the de novo creation of G protein-coupled receptors, which link chemotaxis and phototaxis to all biodiversity.
For comparison, see: Mutation-Driven Evolution
Excerpt:
Mutation… includes nucleotide substitution, insertion/deletion, segmental gene duplication, genomic duplication, changes in gene regulatory systems, transposition of genes, horizontal gene transfer, etc.
My comment: The definition above links mutations to any change in any genome.
See for comparison: Updates of the HbVar database of human hemoglobin variants and thalassemia mutations
Excerpt:
Single nucleotide substitutions or indels [insertions/deletions] can lead to several hemoglobin variants owing to amino acid replacements, while molecular defects [mutations] in either regulatory or coding regions of the human HBA2, HBA1, HBB or HBD genes can minimally or drastically reduce their expression, leading to α-, β- or δ-thalassemia, respectively.
My comment: The facts about nutrient energy-dependent amino acid substitutions link hemoglobin variants from ecological adaptation to healthy longevity and the facts also link molecular defects from mutations to the pathology of α-, β- or δ-thalassemia, respectively. It would be difficult to include facts about biophysically constrained energy dependent cell type differentiation in the context of any other model that links amino acid substitutions to healthy longevity and links mutations to all pathology in all living genera.
See for example: Criticisms of the nutrient-dependent pheromone-controlled evolutionary model
Excerpt:
…James Kohl presents an unsupported challenge to modern evolutionary theory and misrepresentations of established scientific terms and others’ research.
My comment: The claims of a biologically uninformed undergraduate student reviewer were placed into the context of modern evolutionary theory, which involves Masatoshi Nei’s simple-minded revision of neo-Darwinian pseudoscientific nonsense. Nei does not compare his theory of mutations to the facts about nutrient energy-dependent fixation of amino acid substitutions in supercoiled DNA. The problem appears to be the use of the term “mutation” in the textbook published on the same day as my 2013 review was published.
I linked the energy-dependent fixation of amino acid substitutions to all healthy longevity. Nei’s textbook misrepresentations did not link anything to healthy longevity, but linked mutations to what I claimed are nutrient-dependent pheromone-controlled polycombic ecological adaptations.
I failed to include what is known about energy-dependent codon optimality in the context of polycombic ecological adaptations because there was no experimental evidence of biologically-based cause and effect to support those claims at the time of our 1996 review or my 2013 review. For comparison, there has never been any experimental evidence of biologically-based cause and effect to support claims about mutation-driven evolution. Simply put, nothing known to serious scientists about cell type differentiation suggest that mutation-driven evolution can occur.
For comparison, see: New analysis of big data sheds light on cell functions
Excerpt:
With today’s technology, scientists are able to generate data about a cell’s or organism’s complete set of genes, proteins, RNA profiles, metabolites and much more—known as omic data. Using omic data, scientists can model complex biological interactions and gain a more holistic view of different cellular processes.
Reported as: Scientists edit gene mutations in inherited form of anemia
Excerpt:
The researchers found that the technique corrected the mutation to such a degree that the mice no longer had symptoms of thalassemia. After 140 days, they tested hemoglobin levels in the animals and found them to be normal.
“The fundamental result here is that with nanoparticles containing PNAs, along with template DNA, and simple IV infusion of molecules, we achieved enough gene editing to effectively cure the anemia in mice that had thalassemia,” Glazer said.
My comment: The ability to correct the mutation requires a link from energy-dependent changes in hydrogen-atom transfer in DNA base pairs in solutions such as blood. That’s how their IV therapy works. It changes the microRNA/messenger RNA balance and that forces the innate immune system to repair the damaged DNA.
See also: Two novel loci, COBL and SLC10A2, for Alzheimer’s disease in African Americans
Excerpt:
Two SNPs at novel loci, rs112404845 (P = 3.8 × 10−8), upstream of COBL, and rs16961023 (P = 4.6 × 10−8), downstream of SLC10A2, obtained genome-wide significant evidence of association with the posterior liability.
Reported as: Study Identifies Two New Genes Responsible for Alzheimer’s in African Americans
Excerpt:
In 2013, a genome-wide association study of AD in more than 5,500 African Americans identified two genetic risk factors for AD. This study looked at genetic variants across subjects’ entire genome and compared their frequency in cases versus controls.
By doing so they were able to identify two new genes (COBL and SLC10A2) associated with risk of AD in African Americans.
My comment: The author’s study results link hydrogen-atom transfer in DNA base pairs in solution to energy-dependent changes in the microRNA/messenger RNA balance. The neuroscience news report claims they identified two new genes. The neuroscience news report then links the genes — instead of the energy-dependent changes — to the disease in a human population. Many African Americans are examples of how ecological variation has been linked to polycombic ecological adaptation via hemoglobin variants. The adaptations include amino acid substitutions linked to the stability of organized genomes in populations where malaria is endemic. Failed adaptations are included in examples of virus-driven energy theft linked to mutations and the pathology of Alzheimer’s disease.
My comment: The ability to edit out gene mutations clearly links RNA-mediated amino acid substitutions to supercoiled DNA and all biodiversity.
See also: Inventing neo-Darwinism
See also: Pioneering Geneticist Explains Ambitious Plan to “Write” the Human Genome
Excerpt:
…he notes that with an editing tool like CRISPR, one base out of many can be altered, but with a synthesis approach, a hundred edits could be made. This sort of change, he tells JAMA, could make a cell resistant to multiple viruses.
Will anyone be able to stop the hecatombic evolution of pathology via the polycombic ecological adaptation, which links autophagy to healthy longevity via protection of organized genomes from virus-driven entropy?
See also: Yale scientists edit gene mutations in inherited form of anemia Genetics & Genomics
A new gene therapy is being tested for its ability to treat thalassemia, a form of anemia caused by genetic mutations. So far, scientists have successfully corrected gene mutations causing the disease in mice, and now researchers are interested in seeing if the same approach will work effectively in humans.
“The fundamental result here is that with nanoparticles containing PNAs, along with template DNA, and simple IV infusion of molecules, we achieved enough gene editing to effectively cure the anemia in mice that had thalassemia. We demonstrated we have extremely low off-target effects.”
See for comparison:
Excerpt:
Each microRNA mimic in our pipeline is designed to replicate the activity of a single tumor suppressor miRNA and regulate the expression of key oncogenes across multiple oncogenic pathways which can prevent proliferation and induce apoptosis in cancer cells.
See also: VACRC Projects
Excerpt: Future Projects
The Influence of Carbon Dioxide Enhancement on Plant Growth Thermoregulation in Honey Bees Biochemistry and Taxonomy in Pine Trees The Formation of Multiple Tree Rings in Bristlecone Pine TreesThe VACRC suddenly seems willing to take everything I have claimed about RNA-mediated cell type differentiation during the past twenty years and begin to investigate the claims. This would have been a desirable outcome 20 years ago, but now it might prevent progress via use of my model. The model links energy-dependent changes from angstroms to ecosystems in all living genera, it and links virus-driven energy theft to all pathology.
The Pacific Yew Tree and production of taxol is an example of how the physi0logy of reproduction in soil bacteria can be linked from plant growth to the honeybee model organism of thermoregulation and behavior, which must be linked to the biochemistry and taxonomy of all species. That becomes meaningful via the explanatory power of a model that links RNA-mediated amino acid substitutions to all energy-dependent biodiversity via the conserved molecular mechanisms of polycombic ecological adaptation we detailed in our 1996 review.
However, when others wait too long to accept a model that may already have led to a paradigm shift, they may also realize it. That fact was addressed by Kaveli Kull in the context of next week’s meeting of the Royal Society.
See: Kalevi Kull: Censorship & Royal Society Evo Event
Excerpt:
Nobody wants to belong to the party of losers. One of the best strategies in such a case is evidently an interpretation of the change as a gradual accumulation of knowledge while their work has always been at the cutting edge.
My comment: Some work by young earth creationists has been at the cutting edge since 1996, as indicated here: Where do viruses come from?
Excerpt:
‘Viruses tend to keep nutrients away from the big stuff and keep them going around in the little stuff,’ says Fuhrman. If so, viruses have shaped the entire structure of the ecosystem.”9
My comment: 9 is Holmes, B. (1996) Who Rules the Waves? New Scientist 152(2054):8-9, supp I have not read it in its entirety but the claim fits into the context of everything else I have learned about physics, chemistry, and conserved molecular mechanisms of RNA-mediated cell type differentiation, which appears to be biophysically constrained in all living genera via their nutrient-dependent pheromone-controlled physiology of energy-dependent reproduction.