Hemochromatosis, known as the “Celtic” disease (44), is a variably penetrant recessive disorder, potentially fatal, due to excessive retention of dietary iron. It has been suggested that the high frequencies of both C282Y and H63D are due to heterozygote advantage related to nutritional advantage in Neolithic iron-poor diets (52), mitigation of celiac disease (53), and increased resistance to parasitic infection (54). To our knowledge, our data provide the first evidence for known Mendelian disease alleles in ancient genomes and mark the associations of both hemochromatosis alleles with the island of Ireland as ancient.
My comment: C282Y is caused by a guanine to adenine transition at nucleotide 845 (TGC—TAC) that is linked to the nutrient-dependent RNA-mediated substitution of cysteine (C) by tyrosine (Y) at amino acid position 282 in the HFE protein. H63D results in the substitution of histidine (H) by aspartate (D) at amino acid position 63 in the HFE protein. The nutrient-dependent RNA-mediated amino acid substitutions are reported to be mutations in the context of other reported mutations.
…more than 10 other missense mutations that cause amino acid substitutions have been documented. A missense mutation indicates a change in DNA, resulting in an amino acid substitution.
My comment: Nutrient energy-dependent base pair substitutions link nutrient-dependent microRNAs to adhesion proteins and the stability of supercoiled DNA that protects organized genomes from virus-driven genomic entropy in all living genera. The molecular mechanisms that link nutrient-dependent non-coding RNAs to DNA repair and healthy longevity were placed into the context of the cellular strategic defense mechanism against viruses.
These findings have revealed an lncRNA-dependent mechanism that regulates a highly dosage-sensitive family of RNA binding proteins, uncovering a post-transcriptional regulatory axis that maintains genomic stability in mammalian cells.
My comment: NORAD is linked to nutrient-dependent RNA-mediated cell type differentiation and genomic stability in mammalian cells that is only possible in the context of the pheromone-controlled physiology of reproduction that enables fixation of RNA-mediated amino acid substitutions in organized genomes.
See for comparison: Insulator dysfunction and oncogene activation in IDH mutant gliomas
Mutant IDH protein produces a new onco-metabolite, 2-hydroxyglutarate, which interferes with iron-dependent hydroxylases, including the TET family of 5′-methylcytosine hydroxylases3, 4, 5, 6, 7. TET enzymes catalyse a key step in the removal of DNA methylation8, 9.
My comment: The heterozygote advantage linked from the nutritional advantage in Neolithic iron-poor diets to the mitigation of celiac disease and increased resistance to parasitic infection can be compared in the context of fixed amino acid substitutions in a modern human population.
- Nutrient-depenedent pheromone-controlled fixation and the post-transcriptional regulatory axis that maintains genomic stability in mammalian cells link everything currently known to serious scientists about cell type differentiation to nutrient-dependent RNA-mediated amino acid substitutions.
- Mutant IDH proteins link iron-dependent hydroxylases from the 5′-methylcytosine hydroxylases to the removal of DNA methylation the makes supercoiled DNA subject to damage by viral microRNAs. The viral microRNAs link nutrient energy theft by viruses to perturbed protein folding and all pathology.
- All of pathology is linked to gain of function mutations in brain cancer via information from the CDC for health professionals.
- Some health care professionals are taught to believe that mutations are beneficial.
- At the same time they are being taught to ignore the links from nutritional epigenetics to pharmacogenomics — except when drug therapy will be used to treat the pathology that could probably have been prevented.
See for comparison: Neocortical Tet3-mediated accumulation of 5-hydroxymethylcytosine promotes rapid behavioral adaptation
These authors bring to bear what is currently known to serious scientists about biophysical constraints on ecological adaptation. The constraints have been ignored by theorists who seem not to realize that life is nutrient-dependent. There are no beneficial mutations — despite the claims of theorists.
The fact that RNA-mediated amino acid substitutions are linked from nutrient stress and social stress to all morphological and behavioral phenotypes in all individuals of all living genera, seems to have escaped the notice of these authors and others who are reporting results from their studies link these, that Jay R. Feierman regurgitated on 12/30/15, in a series of posts to the International Society for Human Ethology’s (ISHE) Human Ethology yahoo group:
Feierman continues to doggedly pursue information that is never placed into a cohesive representation of biologically-based cause and effect. After removing me from the group because I would not answer a question about RNA-mediated events with a yes or no answer, he links my comments on
Beyond DNA Epigenetic mechanisms of inheritance (December 1, 2015) to his nonsensical claims:
On 11/1/12: “Random mutations are the substrates upon which directional natural selection acts.”
On 2/16/13 : “Random gene mutation is the variance generator upon which natural selection operates.”
On 2/23/13: “…random genetic mutations generate the substrate upon which natural selection can act. Random genetic mutations create structural variations in protein enzymes…”
Feierman’s nonsense is echoed in the claims of researchers who have been taught by people like him to become biolgoically uninformed science idiots.
See for example: Origins of De Novo Genes in Human and Chimpanzee
Our results indicate that the expression of new loci in the genome takes place at a very high rate and is probably mediated by random mutations that generate new active promoters. These newly expressed transcripts would form the substrate for the evolution of new genes with novel functions.
My comment: The experience-dependent de novo creation of olfactory receptor genes links UV light from hydrogen-atom transfer in DNA base pairs to nutrient-dependent RNA-mediated cell type differentiation in all cell types of all individuals of all living genera.
The links from the energy of sunlight via atoms to ecosystems have been established by serious scientists at every level of investigation, and they have been reported in the context of experimental evidence of biologically-based cause and effect.
The experimental evidence links metabolic networks to genetic networks in organized genomes via microRNAs, adhesion proteins, and supercoiled DNA that protects the organized genomes from virus-driven entropy.
The fact that none of this information is included in the report on de novo gene creation attests to how much pseudoscientific nonsense about mutations and evolution has been taught to the researchers who published their results and to anyone involved in the peer review process at PLOS Genetics.
All serious scientists will continue to laugh at those who choose to remain biologically uninformed until they learn how to link RNA-mediated events to morphological and behavioral phenotypes and quit touting pseudoscientific nonsense.