Nutrient-dependent pheromone-controlled alternative splicings and the amino acid substitutions that result in de novo gene creation are responsible for all differences in all cell types of all individuals of all species that have adapted to ecological variation. Mutated genes are found in cells associated with diseases and disorders, not adaptations.
Yesterday, I mentioned Real-Time Evolution of New Genes by Innovation, Amplification, and Divergence. “Nutrient-driven gene duplication resulted in nutrient-driven differentiation of cell types that occurred via alternative splicings of pre-mRNA and amino acid substitutions that stabilized organism-level thermoregulation, which is controlled by the physiology of reproduction. Unfortunately, these researchers reported their results in terms of mutation-initiated natural selection.”
Yesterday, in my post on Zimmer’s ignorance, I mentioned that “… two additional amino acid substitutions show up in the context of comparisons with other primates. For example, the amino acid sequence of the FOXP2 gene is highly conserved across mammals and the amino acid sequences are identical in rhesus macaques, gorillas, and chimpanzees. Thus, the additional amino acid substitutions in humans appear to be the clearest link to the neuroscientifically established ability to talk and to understand what others are saying.”
I added that “…Dobzhansky also noted the finding, in sickle-cell disease “‘…that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule.”
Today, I read “Many rare disorders are caused by gene mutation, like sickle cell anemia.” Sickle cell is NOT caused by a gene mutation. Sickle cell is caused by the substitution of a single amino acid. If the substitution is viewed in the context of a mutated gene, researchers may never grasp the difference between the de novo creation of a gene that enables ecological adaptation and a mutated gene that causes cancer. Here’s the difference:
The substitution of valine in place of glutamic acid in the beta chain of the hemoglobin molecule allows adaptation in an ecological environment of mosquito-borne malarial parasites. Carriers of one amino acid substitution are more likely to reproduce than to die from malaria. Only when their offspring end up with one gene from each parent that has the amino acid substitution will the combination of two amino acid substitutions not be an adaptation linked to increased reproductive fitness. Instead, the oxygen carrying capacity of the blood will be compromised by two amino acid substitutions in their genome. One amino acid substitution has not been edited out of the population. It is required to facilitate nutrient-dependent pheromone-controlled reproduction, and the physiology of reproduction is not compromised by only one amino acid substitution.
However, the senior author of Combinatorial effects of multiple enhancer variants in linkage disequilibrium dictate levels of gene expression to confer susceptibility to common traits would like people to believe that the combined effects on gene expression of “multiple enhancer variants” should be viewed as if the effects represented a paradigm shift. “This is a paradigm shift for the field with respect to pinpointing the genetic causes of common disease susceptibility,” Scacheri said.” A Google search on the phrase: multiple enhancer variants (without quotes) took me to the Wikipedia entry on Alternative splicing
The confusion about what constitutes a paradigm shift in the context of genetic causes of common disease susceptibility is due to the failure to consider what we (TB) wrote in 1996 about the importance of alternative splicings in the context of sex differences. “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).”
Anyone touting “multiple enhancer variants” in the context of alternative splicings is contributing to the ongoing ignorance of biologically-based cause and effect. That ignorance is exemplified by Zimmer. Those who want to tout their works on multiple enhancer variants as if they represented “…a paradigm shift for the field with respect to pinpointing the genetic causes of common disease susceptibility…” are actually continuing to delay recognition that the paradigm shift took place in 1996. We linked alternative splicings to nutrient-dependent pheromone-controlled synthesis of specific proteins and to sex differences sans mutations theory. “That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.”
It is time to consider sex differences in cell types that are associated with sex differences in diseases in the same context as we should have been considering many diseases and disorders that are nutrient-dependent and pheromone-controlled via epigenetic effects of olfactory/pheromonal input. The epigenetic landscape becomes the physical landscape of DNA in the organized genome of invertebrates and vertebrates via the de novo creation of olfactory receptor genes, not via mutations. Creation of new genes is what enables ecological adaptation. Mutations do not initiate natural selection and evolution is not mutation-driven evolution.
Species diversity is nutrient-dependent and the physiology of reproduction is pheromone-controlled. That’s THE paradigm shift. It requires those who currently think in terms of mutations theory to start thinking about cause and effect, and stop touting beneficial mutations or multiple enhancer variants as if there were any experimental evidence that suggests they result in ecological adaptations in any cell of any individual of any species on this planet. Nutrient-dependent pheromone-controlled ecological adaptations biophysically constrain mutations. Ecological adaptations also constrain “multiple enhancer variants” except when nutrient stress or social stress overcome the conserved molecular mechanisms that have enabled ecological adaptation in all species.
James V. Kohl detailedl how quantized energy-dependent microRNA biogenesis links the pheromone-controlled physiology of reproduction to biophysically constrained viral latency and healthy longevity. Links from what organisms eat to the enzyme-dependent metabolism of food also link metabolic networks to microRNA-mediated genetic networks in the context of RNA interference. Drug therapies alter RNA interference by altering cell type differentiation in all cells of all individuals of all species. For comparison, during the past 26 years, Kohl has detailed how the chemistry of protein folding is biophysically constrained at every level of biological organization by conserved molecular mechanisms.