Multiple haplotype-resolved genomes reveal population patterns of gene and protein diplotypes

Excerpt: “The CDP showed a significant overrepresentation of certain gene ontology (GO) groups (global tests Po0.001–0.009), using the programme FUNC23 (Methods). These groups included GPCRs, in particular olfactory receptors (ORs), and other membrane and cell-surface proteins, as well as proteins related to the immune system, such as the MHC (Class I and II), and drug metabolism…”

My comment: Biodiversity “…converges upon a ‘common diplotypic proteome (CDP)’, a distinctive subset of genes preferentially encoding two different proteins.” In that context, the importance of nutrient-dependent amino acid substitutions to the de novo creation of olfactory receptors (ORs) and other membrane and cell surface proteins cannot be overstated.

For example, this new evidence now also links the epigenetic effects of food odors associated with nutrient uptake to the de novo creation of olfactory receptors. The de novo creation of olfactory receptors links nutrient uptake to receptor-mediated behavior associated with cell type differentiation at the level of epigenetically effected  MHC / immune system differences. The differences are linked to what is currently known about the pharmacogenomics of drug metabolism and the nutritional epigenetics of health and disease.

Reported as:

Duality in the human genome

Excerpt: “More than 85 percent of all genes have no predominant form which occurs in more than half of all individuals. This enormous diversity means that over half of all genes in an individual, around 9,000 of 17,500, occur uniquely in that one person – and are therefore individual in the truest sense of the word.

The gene, as we imagined it, exists only in exceptional cases. “We need to fundamentally rethink the view of genes that every schoolchild has learned since Gregor Mendel’s time.”

My comment: We also need to rethink the interpretation of Darwin’s works, which were placed into the context of population genetics by theorists who knew nothing about biologically-based cause and effect. Observed changes in morphology were placed into the context of an invented theory that defined the changes as if they were caused by mutations in genes. I reiterate: “We need to fundamentally rethink the view of genes…” Let’s rethink the view of genes in the following context:

“[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. The anglophone tradition was taught. I was taught, and so were my contemporaries, and so were the younger scientists. Evolution was defined as “changes in gene frequencies in natural populations.” The accumulation of genetic mutations was touted to be enough to change one species to another…. No, it wasn’t dishonesty. I think it was wish fulfillment and social momentum. Assumptions, made but not verified, were taught as fact.” — excerpted from Replace the Modern Synthesis (Neo-Darwinism): An Interview With Denis Noble

That powerful recollection by Suzan Mazur, author of The Altenberg 16: An Exposé of the Evolution Industry may reflect her personal bias against evolutionary theory. Indeed, her exposé has received an abundance of criticism, as would be expected from those still touting their pseudoscientific nonsense about genes, mutations and evolution.

Does it matter if her beliefs were biased when evidence of “duality in the human genome” now attests to the fact that her beliefs are supported? Experimental evidence now links epigenetic imprinting across species via the conserved molecular molecular mechanisms that we placed into this perspective in our 1996 Hormones and Behavior review? Here’s a single paragraph from our review, which also exposed the “Evolution Industry”.

Excerpt: “Molecular epigenetics
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: We now know that these alternative splicings are nutrient-dependent and that RNA-directed DNA methylation links them from from ecological variation to RNA-mediated amino acid substitutions that differentiate all cell types in all individuals of all species via conserved molecular mechanisms. It may never become clearer that cell type differentiation is nutrient-dependent and that fixation of amino acid substitutions requires the metabolism of nutrients to species-specific pheromones.

Pheromones control the physiology of reproduction, which enables fixation of the amino acid substitutions in the DNA of organized genomes. It is time to compare ridiculous theories about mutations invented by population geneticists to established facts about how experience-dependent de novo creation of olfactory receptors links ecological variation to ecological adaptations. It’s as simple as 1-2-3.

1) Amino Acid Residues Contributing to Function of the Heteromeric Insect Olfactory Receptor Complex  “Our results suggest that both the ligand-selective Or subunit and the Orco co-receptor contribute to cation channel activity and that some amino acid residues near the carboxy terminus of both subunits are important for Or-Orco channel function.”

2) orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET “orco mutant olfactory sensory neurons have greatly reduced spontaneous activity and lack odour-evoked responses.”

3) Evolution of mosquito preference for humans linked to an odorant receptor “Our results provide a rare example of a gene contributing to behavioural evolution and provide insight into how disease-vectoring mosquitoes came to specialize on humans.” Also see: “Extended Data Figure 3 | Amino acid differences of major Or4 protein alleles.  Dots represent amino acid differences with respect to the genome reference, not an inferred ancestor.”

1) amino acids and olfactory receptor complexes are important for

2) olfactory sensory function and odor-evoked responses, which are perturbed by mutations but

3) established in the context of amino acid substitutions.

In my model, nutrient-dependent amino acid substitutions link the metabolism of nutrients to species-specific pheromones that control the physiology of reproduction in species from microbes to man. In accord with the findings above, the amino acid substitutions do not infer a link to a common ancestor. Theories about common ancestors belong to population geneticists, not serious scientists who understand biologically-based cause and effect.

See for comparison: “…mutations provide the “raw material” upon which the mechanisms of natural selection can act.”

Ecological variation is the raw material by which natural selection can drive evolutionary divergence [1–4].

Amino acid substitutions link ecological variation and the epigenetic landscape to the physical landscape of DNA in the organized genomes of all species via conserved molecular mechanisms that are bio-physically constrained by the chemistry of protein folding. Pheromone-controlled ecological adaptations are manifested in the morphological and behavioral diversity of all species.

Mutations perturb protein folding, which is why they cannot lead to the evolution of biodiversity.

Odor-induced de novo creation of olfactory receptors links nutrient-dependent amino acid substitutions to their pheromone-controlled fixation and genome stability in species from microbes to man via conserved molecular mechanisms. See for examples: Nutrient-dependent/pheromone-controlled adaptive evolution: a model

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