Sudden death indel polymorphism
…different alleles of rs10692285 could alter the local structure of RYR2 mRNA and microRNA (miRNA) binding.
See for comparison: Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant
The differences between the 370A knockin mouse phenotypes and those of loss- and gain-of-function models emphasize the advantage of a more accurate mouse model.
In this study an adaptive variant links the mouse model to a modern human population via changes in the microRNA/messenger RNA balance. The adaptive variant is referred to as rs3827760, but it is also known as 1540T/C, 370A or Val370Ala.
It is an energy-dependent single nucleotide polymorphism in the ectodysplasin A receptor EDAR gene on chromosome 2. Reporting it as the Val370Ala amino acid substitution links the energy-dependent change in the base pair to the biophysically constrained pheromone-controlled fixation of the amino acid substitution via the physiology of reproduction, which links autophagy to supercoiled DNA and all energy-dependent biodiversity in all living genera.
Simply put, the supercoiled DNA protects all organized genomes from virus-driven entropy. Supercoiled DNA is the “energy as information-dependent” source of all biodiversity. See for details:
The anti-entropic force of virucidal ultraviolet light links guanine–cytosine (G⋅C) Watson–Crick base pairing from hydrogen-atom transfer in DNA base pairs in solution to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy. For example, protection of DNA from permanent UV damage occurs in the context of photosynthesis and nutrient-dependent RNA-directed DNA methylation, which links RNA-mediated amino acid substitutions to DNA repair. In the context of thermodynamic cycles of protein biosynthesis and degradation, DNA repair enables the de novo creation of G protein coupled receptors (GPCRs). Olfactory receptor genes are GPCRs. The de novo creation of olfactory receptor genes links chemotaxis and phototaxis from foraging behavior to social behavior in species from microbes to humans. Foraging behavior links ecological variation to ecological adaptation in the context of this atoms to ecosystems model of biophysically constrained energy-dependent RNA-mediated protein folding chemistry. Protein folding chemistry links nutrient-dependent microRNAs from microRNA flanking sequences to energy transfer and cell type differentiation in the context of adhesion proteins, and supercoiled DNA that protects all organized genomes from virus-driven entropy.
Antagonist Peter Berean repeatedly asserts that energy is not information. He has invented the term bio-functional information in an attempt to continue linking mutations to evolution, which is what was done in: Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant.
For contrast, An insertion/deletion polymorphism within 3’UTR of RYR2 modulates sudden unexplained death risk in Chinese populations links virus-driven energy theft to the pathology via loss of function associated with the insertion/deletion (indel) polymorphism. The energy-dependent polymorphism links different alleles of rs10692285 from amino acid substitutions in viruses to sudden unexplained death risk in Chinese populations. There is no mention of the fact that the amino acid substitutions that stabilize viruses would otherwise link an energy-dependent amino acid substitution from a single base pair to cell type differentiation in the sudden death-causing cells.
That fact can be viewed in the context of my model and these two reports:
1) Structural diversity of supercoiled DNA (supercoiling)
2) Structural Dynamics and Mechanochemical Coupling in DNA Gyrase (negative supercoiling)
See also: Analysis of 6,515 exomes reveals the recent origin of most human protein-coding variants
Reported as: Past 5,000 years prolific for changes to human genome
Of 1.15 million single-nucleotide variants found among more than 15,000 protein-encoding genes, 73% in arose the past 5,000 years, the researchers report.
On average, 164,688 of the variants — roughly 14% — were potentially harmful, and of those, 86% arose in the past 5,000 years. “There’s so many of [variants] that exist that some of them have to contribute to disease,” says Akey
Once again, we see that theorists must learn the difference between an energy-dependent RNA-mediated amino acid substitution and a mutation before they can grasp the levels of complexity that must be integrated into models of biophysically constrained energy-dependent biodiversity.
The problem that most theorists have with the concept of energy as information is due to the fact that they do not know the difference between an energy-dependent amino acid substitution and a mutation, which is caused by virus-driven energy theft.
See: Virus-driven mutation or amino acid substitution
Pseudoscientists invented a theory based on de Vries definition of mutation, and more theories were added in the absence of experimental evidence that could link top-down causation to cell type differentiation in all genera. Instead of energy-dependent cell type differentiation, we got this:
For comparison, see: Mutation-Driven Evolution
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
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.
Unfortunately, some medical laboratory scientists are still not getting the message about the difference between a mutation and fixation of an amino acid substitution.
See also the attacks on my credibility and my model in this discussion attempt, which drew participation and more antagonism from the group’s administrators, John L. Leonard and Peter Berean.