Molecular Diagnostics (April 6 and 7, 2016)
Available on demand: Molecular Medicine in Healthcare: The Personalized Medicine Initiative
Pieter Cullis answered this question at 41:50
In the context of nutritional epigenetics and Precision Medicine, do you think RNA-mediated amino acid substitutions link changes in the microRNA/messenger RNA balance from the innate immune system to healthy longevity and/or to pathology?
Pieter Cullis Pieter Cullis answered this question at 1:01
Do you think that neo-Darwinian theories, which link mutations to evolution have prevented scientific progress towards Precision Medicine?
My comment: The links from energy-dependent changes in base pairs to the microRNA/messenger RNA balance and links from the immune system and RNA-mediated amino acid substitutions to healthy longevity and / or virus-driven energy theft and pathology are clear. I asked Pieter Cullis about neo-Darwinian theories because I consistently see attempts by theorists to link physics and chemistry from mutations to natural selection and evolution. The attempts become more ridiculous each week.
See: April 8, 2016 Ribose and related sugars from ultraviolet irradiation of interstellar ice analogs
Their theory about the origin of life in outer space can now be compared to my model of energy-dependent biodiversity on Earth. See for instance: Ultraviolet Absorption Induces Hydrogen-Atom Transfer in G⋅C Watson–Crick DNA Base Pairs in Solution
Compare ultraviolet (UV) radiation and UV absorption in interstellar ice analogs to UV absorption on Earth, which links energy-dependent base pair changes and RNA-mediated protein folding chemistry to biophysically constrained life via the physiology of reproduction in all living genera. For consistency, remember to place all claims about UV radiation and UV absorption into the context of the creation of the innate immune system, which links metabolic networks to genetic networks that ensure the physiology of reproduction in all living genera.
For instance, to establish the consistency across disciplines, start in outer space and link angstroms to ecosystems as these two groups tried to do.
See for example: Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system
Does UV irradiation of interstellar ice analogs link weekend evolution of the bacterial flagellum to hominid genome evolution outside the context of UV absorption and the physiology of nutrient energy-dependent reproduction on Earth?
See also: Clustered mutations in hominid genome evolution are consistent with APOBEC3G enzymatic activity
Can you explain how UV irradiation of interstellar ice analogs and clustered mutations link enzymatic activity from weekend evolution of the bacterial flagellum to hominid genome evolution. If so, your explanation could refute claims by Einstein, Schrodinger, Dobzhansky and others who have collectively linked theories and experimental evidence of biologically-based cause and effect to de novo gene creation and the creation of the innate immune system, which links metabolic networks and genetic networks to supercoiled DNA.
The experimental evidence links supercoiled DNA to protection of organized genomes from virus-driven entropy. Alternative models that link biologically-based cause and effect could be used to refute claims about the need for the anti-entropic energy of the sun, which links energy-dependent changes in base pairs to supercoiled DNA. Do you have an alternative model that explains how all organized genomes are protected from virus-driven entropy? If so, how does your model link UV radiation and UV absorption from ecological variation to nutrient-dependent pheromone-controlled ecological adaptations in species from microbes to humans?
If there is no other model for comparison to my model, neo-Darwinists have prevented the scientific progress that should have led to the Precision Medicine Initiative from the details of molecular epigenetics we included in our section on molecular epigenetics in our 1996 Hormones and Behavior review.
From Fertilization to Adult Sexual Behavior
It is now understood that certain genes undergo a process called “genomic or parental imprinting.” Early in embryonic development attached methyl groups become removed from most genes. Several days later, methyl groups are reattached in appropriate sites. Fascinatingly, some such genes reestablish methylation patterns based upon whether the chromosomal segment carrying the gene came from maternal or paternal chromosomes. These sexually dimorphic patterns are labeled genomic or parental imprinting, and these imprintings are inheritable but non-genetic modifications of specific genes (Razin and Shemer, 1995; Reik, 1989; Surani, 1991; Zuccotti and Monk, 1995).
There are at least 16 known genomic-imprintings in the human genome and each particular imprint depends upon whether the chromosome is of maternal or paternal origin (Hurst, McVean, and Moore, 1996). Furthermore, these inherited imprintings are physiologically important and are capable of sex-specific effects as evidenced in the Prader-Willi and Angelman syndromes (congenital disorders with physical and mental characteristics) derived from imprinting anomalies in a specific region of chromosome 15 (Driscoll, Waters, Williams, Zori, Glenn, Avidano, and Nicholls, 1992).
Genomic-imprinting is also manifest in specific parts of the X-inactivation region’s related XIST gene. Here male- and female-specific methyl-group patterns participate in X-inactivation in females and also in the preferential inactivation of the paternal X in human placentae of female concepti (Harrison, 1989; Monk, 1995). This process indicates that tissues of the early conceptus can sense and react differentially to epigenetic sexual dimorphisms on the female conceptus’ own two X chromosomes. Furthermore, variations of X-inactivation patterns often account for traits discordance in monozygotic twin females. In other words, they are often found to have nonidentical patterns of X-inactivation, yielding differing expression of noticeable X-linked traits (Machin, 1996).
Pollard (1996) has hypothesized that sexual orientation may be encoded within imprinted genes. In a manner that also challenges the Gn–H–B paradigm she posits that genomic imprinting, as a preconception event, enables a gene to be “able to switch through different states of potential activity from the incomplete to the fully penetrant state resulting in a continuum of orientations ranging from asexual, through graded bisexual to homosexual” (p. 269). And she envisions these modifications to be potentially prompted by social environmental events.
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.
A potential ramification of epigenetic imprinting and alternative splicing may be occurring in Xq28, a chromosomal region implicated in homosexual orientation (Brook, 1993; Hu, Pattatucci, Patterson, Li, Fulker, Cherny, Kruglyak, and Hamer, 1995; Turner, 1995). Xq28 contains one of the X chromosome’s two pseudoautosomal regions (PARs), adjoins the telomere, and has various means of gene expression control (D’Esposito, Ciccodicola, Gianfrancesco, Esposito, Flagiello, Mazzarella, Schiessinger, and D’Urso (1996). Xq28, therefore, is a chromosomal region that has many of the heterochromatic and telomeric characteristics that participate in sexual determination and behavior in other species.
See also, our introduction to RNA-mediated cell type differentiation in the context of the nutrient-dependent pheromone-controlled “conditions of life,” which Darwin placed before natural selection in the context of important considerations for any additional theories.