“…the only worthwhile biology is molecular biology. All else is “bird watching” or “butterfly collecting.” Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists!” — Dobzhansky (1964)
“The working hypothesis now in vogue is that the process of adaptation to the environment is the main propellant of evolutionary change…. It remains, however, not only to convince the doubters but, what is more important, to discover just how the challenges of the environment are translated into evolutionary changes.” Dobzhansky (1964)
“… hemoglobin S differs from A in the substitution of just a single amino acid…” Dobzhansky (1964)
Bird watchers in the lab (mutations cause adaptations)
The Genetic Basis of Escherichia coli Pathoadaptation to Macrophages (with my emphasis)
Excerpt: “Our results demonstrate that bacteria can evolve remarkably fast, and acquire adaptations increasing survival inside macrophages and/or ability to escape engulfment. The mechanism underlying this pathoadaptive process involves the accumulation of mutations caused by transposon insertions, increasing pathogenicity in vivo. These findings reveal the remarkable fast pace at which bacteria can evolve to escape a central component of the host innate immunity, namely macrophages.”
My comment: They used a combination of what they call “experimental evolution” with phenotypic characterization, genome sequencing and mathematical modeling. They addressed how fast…” adaptation occurred due to competition between distinct haplotypes and the successive accumulation of beneficial mutations.” They observed differences in colony types. That is: “…distinct colony morphologies emerged in all populations…”
No experimental evidence suggests that mutations are fixed in the organized genome of any species from microbes to man. Thus, the accumulation of beneficial mutations in not possible. However, in this report, the fact that “…small colony variants SCVs increased in frequency but failed to reach fixation…” was not a problem. Despite the fact that no experimental evidence supports any claims about accumulated beneficial mutations, mathematical models of population genetics suggest that — given enough time — fixation of mutations. Thus, despite no experimental evidence to support their claim, they claim the accumulation of beneficial mutations somehow occurs. Somehow, the SCVs that contained the fixed accumulation of beneficial mutations would then be fixed in the population.
The authors conclude: “This pathoadaptive process and the complex dynamics of the evolved phenotypes can be reasonably described by a model of clonal interference, where distinct haplotypes, carrying new transposon insertions and other mutations, increase in frequency and compete for fixation.”
This is how evolutionary theory kills people. The authors attribute pathogenicity of E. coli to accumulated mutations. They ignore the fact that amino acid substitutions differentiate cell types, individuals, and species in all living organisms.
Their approach is similar to that of the early ethologists who observed differences in the morphological characteristics of birds and attributed differences in plumage color and beaks to the role of visual input in sexual reproduction. They never considered whether the physiology of reproduction in birds might be nutrient-dependent and pheromone-controlled via the epigenetic effects of olfactory/pheromonal input on amino acids substitutions. They did not report any evidence that suggested the birds had a sense of smell!
Since the time of their observation-only approach, it has become obvious that morphological characteristics of all species may includes color changes that are due to amino acid substitutions and changes in the physical structure of beaks, mandibles, and teeth. However, no one seems the least bit suspicious of reports that claim cause and effect is due to accumulated mutations. Mutation-driven evolution of E. coli somehow occurs in the absence of experimental evidence because mathematical models clearly support the idea of mutation-driven evolution. The statistically unlikely possibility that experimental evidence in some organism such as E. coli might someday support the theory of mutation-driven evolution is good enough to make the claim that accumulated mutations cause pathogenicity.
Serious scientists in the lab (amino acid substitutions enable adaptations)
Preservation of Protein Dynamics in Dihydrofolate Reductase Evolution (with my emphasis)
Excerpt 1: Escherichia coli dihydrofolate reductase (ecDHFR)1 is a model system used to address the link between enzyme dynamics and function (2-15). DHFRs catalyze the stereospecific reduction of 7,8-dihydrofolate (H2F) to 5,6,7,8-tetrahydrofolate (H4F) through a transfer of a pro-R hydride from the C4 position of reduced nicotinamide adenine dinucleotide phosphate (NADPH) to the C6 atom of the dihydropterin ring of H2F (Scheme 1).
Excerpt 2: Experimental and theoretical studies of the temperature dependence of KIEs in a variety of enzymatic systems suggested that fast dynamics of the reactive complex directly affect the reaction coordinate (25, 27, 38, 39).
My comment: This experimental and theoretical studies have provided in experimental evidence that attests to the dynamic constraints of protein folding, which result in adaptations in enzymes. These adaptations are preserved in species from E. coli to humans. “…it is apparent that evolutionary pressure maintained the native dynamics and narrow DAD distribution at the TRS as DHFR evolved from bacterial toward human enzyme. “Kohen says that his study of the diverging genetic sequences between E. coli and Homo sapiens illustrates the process of evolution at a basic level.”
Why do the experimental and mathematical results from the other study results suggest that mutation-driven evolution occurs at the most basic level in this same organism?
Kohen’s group clearly links E. coli to Homo sapiens via amino acid substitutions that are conserved. They report that “…a four amino acid insertion (PEKN) was introduced early in the enzyme’s evolution and is highly conserved in higher organisms.” Conserved molecular mechanisms in species from microbes to man link amino acid substitutions that are conserved to other amino acid substitutions that differentiate cell types, individuals and species. It is not surprising to see a report on this research that states “At the molecular level, evolution reshaped some of the enzymes that help complete chemical processes — such as converting food into energy — in humans and all other life forms.” The conversion of food into energy is a condition of life.
Mutations perturb the dynamic constraints of protein folding. They do not reshape enzymes to help convert food into energy that enables beneficial amino acid substitutions. Mutations alter the conserved molecular mechanisms incorporated beneficial amino acid substitutions that differentiate “normal” cell types. Mutations perturb protein folding and cause different cell types to become deformed or cancerous.
However, the role of mutations was addressed in this study: “mutations had no effect on the structure of the active site.” Given what is currently known about the role of mutations, which are not fixed in the genome, it appears that their fixation is prevented by nutrient-dependent alternative splicings. The mutations that perturb the thermodynamics of intercellular signaling and the transcription or expression of genes, which enable adaptations via amino acid substitutions, are edited out. They are not fixed, and they cannot be the cause of natural selection.
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.
I posed two questions to discussants in the context of this blog post and natural selection:
1) Does anyone know of any adaptation in any cell type of any individual of any species that is not nutrient-dependent?
2) Does anyone know how the physiology of reproduction of any organism of any species is controlled by anything besides species-specific pheromones?
I was not surprised that a theorist responded from his extremely out-dated perspective.
He wrote: “In yeast = Saccharomyces cerevisiae == there’s a mutation called “ad3” which (among other things) confers a nutritional dependence on exogenous adenine for the yeast cells to live. It also makes the colonies a rather dusty pink color, at least on certain media. If you take an ad3- strain (one that carries the ad3 mutation) and grow say 10^7 of them in a tube of culture medium containing adenine, and then plate them out on a medium that lacks adenine, a few colonies will grow. Genetic analysis will show that these are back or sometimes suppressor mutations of the ad3 mutation (and their colonies are no longer pink). This is an example of “selection.”
Nutrient-dependence is NOT an unalterable biological essence, but can be affected by mutations and therefore by selection. I know this because I’ve done this experiment in the lab.”
My comment: This is precisely the type of misrepresentation that kills. In the hospital microbiology lab, organisms are identified first by their nutrient-dependent pheromone-controlled amino acid substitution-dependent morphology. Rarely is more than one primary pathogen discovered and further identification of its species specificity is facilitated by biochemical testing that includes testing for antibiotic susceptibility.
Although few people would trust an identification of an organism by a theorist who based his identification on observed colony characteristics, medical practitioners must trust the identification that is based on antibiotic susceptibility. Antibiotic susceptibility also indicates which amino acid substitutions have enabled the thermodynamics of intercellular signaling in the organism, which result in organism level thermoregulation.
The biophysical constraints that keep one organism from from mutating to become another organism, result from nutrient-dependent pheromone-controlled amino acid substitutions associated with the organism’s stability. The organism’s thermodynamic stability must be altered by the appropriate antibiotic to quell the infection. And no matter how many generations of organisms continue to grow if the antibiotic doesn’t work, the organism isn’t going to mutate into another organism. It may kill the patient before it’s identified, and that outcome was more common before the ability to identify and treat patients included more than just observing the colony morphology and guessing what might work best to kill whatever the relatively uninformed experimenter thought he had identified based on what he thought were mutations.