From base editing to RNA editing (2)
Digital reconstruction of the Ceprano calvarium (Italy), and implications for its interpretation
A “fresh” (i.e., not yet “fossil”) bone can be plastically deformed before it breaks because it is still rich in collagen and because the calcium crystals that constitute large part of the bony matrix are not yet substituted by other minerals, as happens during the process of mineralization34. Such a diagenetic process may occur in environments that are rich in water, like a riverbed or a perilacustrine paleosol; the latter was probably the case in the Ceprano area5.
The virus-driven degradation of messenger RNA links the diagenetic process in living tissue links to the fossil record via changes that appear to have occurred during the past 5-10,000 years.
See for instance: MicroRNA-32 promotes calcification in vascular smooth muscle cells: Implications as a novel marker for coronary artery calcification
The increased level of calcification in smooth muscle cells, which is associated with increased rates of coronary artery calcification is a clear indicator that the proliferation of viruses in organized genomes causes the negative supercoiling of DNA, which serious scientists have linked to all pathology.
See also: A Post Mortem Case Study: Diffuse Pulmonary Ossification and Sudden Death
Case studies have no explanatory power outside the context of models that link electrons to ecosystems in all living genera. In this case study, it is clear that the pulmonary ossification and sudden death can be placed into the context of my model of nutritional epigenetics.
See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems
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.
Attempts to support theories about random mutations and evolution have failed miserably and have largely been replaced with facts about energy-dependent RNA-mediated cell type differentiation.
See: RNA Editing Possible with CRISPR-Cas13
The tool itself could be further developed, adds computational biologist Eugene Koonin of the National Center for Biotechnology Information who also was not involved in the study. “This paper is not the end of the road,” he says. It’s possible that Cas13b could be fused to a variety of editing enzymes that would allow a range of different sequence changes. The possibilities are numerous, Koonin says, and “the best is still to come.”
This paper is the end of the road for pseudoscientists and biologically uninformed theorists, like Eugene Koonin, who made this ridiculous claim in 2005:
Amino acid composition of proteins varies substantially between taxa and, thus, can evolve. –Jordan et al., (2005) A universal trend of amino acid gain and loss in protein evolution
See for comparison: The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis… (2015) — Eugene Koonin
See also Koonin’s attack on all models of ecological adaptation: Splendor and misery of adaptation, or the importance of neutral null for understanding evolution (2016)
…population genetic theory, combined with the data of comparative genomics, clearly indicates that such a “pan-adaptationist” approach is a fallacy. The proper question is: how has this sequence evolved? And the proper null hypothesis posits that it is a result of neutral evolution: that is, it survives by sheer chance provided that it is not deleterious enough to be efficiently purged by purifying selection. To claim adaptation, the neutral null has to be falsified.
The link from the creation of the sun’s anti-entropic virucidal energy and the physiology of pheromone-controlled reproduction to fixation of RNA-mediated amino acid substitutions in the organized genomes of all living genera is all that is required to claim adaptation for comparison to Koonin’s moronic assertion that the amino acid composition of proteins varies because the composition evolved.
Each time a new claim attests to the facts about energy-dependent RNA-mediated biophysically constrained cause and effect, remember how long those facts have been placed on hold by people like Eugene Koonin and Jay R. Fiereman, who is the moderator of the International Society for Human Ethology’s Yahoo Group.
See this attempt to discuss mysterious DNA changes with Jay R. Feierman who on 7/25/13 wrote:
Variation is not nutrient availability and the something that is doing the selecting is not the individual organism. A feature of an educated person is to realize what they do not know. Sadly, you don’t know that you have an incorrect understanding [of] Darwinian biological evolution.
All DNA modifications are energy-dependent and RNA-mediated. Publications in Science and Nature attest to the foolishness of those who have tried to link base editing and RNA editing to human cell type differentiation without starting with the fact that RNA-mediated amino acid substitutions are food energy-dependent.
Clearly there are no mysterious stress-linked DNA modifications. Nutrient stress and/or social stress cause the proliferation of viruses. Typically the proliferation of viruses is biophysically constrained by food energy and the pheromone-controlled physiology of reproduction in species from microbes to humans.
See “Cytosis” for the game-ending details that placed the nonsense about neutral null falsification back into the historical perspective of the “Dark Ages.”
See also: Tempo and mode of genome evolution in a 50,000-generation experiment (with my emphasis)
Evidence for beneficial mutations
We sought to understand what proportion of the genomic changes in the non-mutator populations was adaptive, and how that proportion changed over time. One line of evidence derives from the expectation that synonymous substitutions—point mutations in protein-coding genes that do not affect the amino-acid sequence—are neutral and should therefore accumulate at a rate equal to the underlying mutation rate20,35. This expectation is not strictly true owing to selection on codon usage, RNA folding, and other effects, but it is generally thought that such selection is extremely weak, affects only a small fraction of sites at risk for synonymous mutations, or both 36,37.
RNA-mediated protein folding chemistry is biophysically constrained. It is nutrient energy-dependent and biodiversity is controlled by the energy-dependent physiology of reproduction. In 2015, Lenski’s group admitted to their lie about the beneficial mutations, with the claim “This expectation is not strictly true owing to selection on codon usage…”
No beneficial mutations have been found by serious scientists. But Lenski’s group clearly indicated they would continue to lie about all aspects of energy-dependent biodiversity. They hoped to make it appear that all energy-dependent biodiversity emerged and then automagically evolved. If they could do that, they knew that their idiot minions were not likely to examine selection for energy-dependent codon usage. But then,
See for comparison: The dynamics of molecular evolution over 60,000 generations
After 10,000 more generations, Lenski’s group reported that standard models of mutation-driven evolution has not been supported by their experimental evidence. Instead, they placed their results into the context of natural selection for energy-dependent codon usage and long-term adaptation, which obviously occurred outside the context of mutation–selection balance and neutral mutation accumulation.
They clearly indicated that the complexity of ecological variation and energy-dependent ecological adaptation must be considered before reporting anything in the context of natural genetic variation. Simply put, they refuted all the pseudoscientific nonsense their past claims caused to be touted by other biologically uninformed theorists. They reported that ecological adaptation occurs outside the context of the mutations and evolution.
But see: Molecular evolution: No escape from the tangled bank
Ecological interactions emerge spontaneously in an experimental study of bacterial populations cultured for 60,000 generations, and sustain rapid evolution by natural selection.
The claim that there is no escape from the tangled bank is true. Joshua B. Plotkin took Lenki’s group’s refutation of mutation-driven evolution and placed it back into the context of the spontaneous emergence of energy-dependent ecological interactions. And then, he again touted the nonsense about evolution by natural selection.
See also: Rapid and Inexpensive Evaluation of Nonstandard Amino Acid Incorporation in Escherichia coli (2017)
…we developed a toolkit for characterizing any Escherichia coli OTS that reassigns the amber stop codon (TAG). It assesses OTS performance by comparing how the fluorescence of strains carrying plasmids encoding a fused RFP-GFP reading frame, either with or without an intervening TAG codon, depends on the presence of the nsAA. We used this kit to (1) examine nsAA incorporation by seven different OTSs, (2) optimize nsAA concentration in growth media, (3) define the polyspecificity of an OTS, and (4) characterize evolved variants of amberless E. coli with improved growth rates.
Even with the tools available, which have refuted all ridiculous theories of mutation-driven evolution, the claims that variants “evolved” continues to plague all serious scientists. It seems that placing the claims that variants evolved into the context of natural selection for energy-dependent codon optimality and the physiology of pheromone-controlled reproduction in all living genera serves no purpose. However, even if biologically uninformed science idiots are not willing to admit that top-down causation requires first consideration for the energy source, there is hope for the future. Most people intuitively understand that the food energy from what organisms eat must be linked to the metabolism of food and the metabolism of food to species-specific pheromones is the only known link from the physiology of reproduction to all biophysically constrained biodiversity in the context of viral latency.
Epigenetic effects must be linked to affects on behavior and the difference between an effect on hormones and an affect of hormones on behavior must be considered in the context of how food odors and pheromones are linked to the physiology of human reproduction by serious scientists.
For example, see: Feedback loops link odor and pheromone signaling with reproduction