Magic, Miracle, or Molecular Mechanism?

The Miracles of Smell and Taste: Evolutionists Cannot Account for the Origin of the Sense of Smell


Professor of Biology John T. Caprio of Louisiana State University states that initially, the sense of smell developed in order to identify amino acid-like chemical substances soluble in water. The ability to determine molecules floating in the air is an adaptation of that original mechanism.96 (p. 106)

How The Nose Knows: Research On Smell Boosted


In an interesting side note, Caprio observed that a pheromone which excites sex in an elephant is the same one that excites sex in a moth.

Origins of magic: review of genetic and epigenetic effects

What is already known on this topic

  • Magical abilities may be heritable

  • Complete family lineages to study this topic have only recently become available

What this study adds

  • Some components of magical ability clearly have a genetic basis

  • This is not a simple single gene effect and may be related to “magical enhancer” elements

My comment: Is life about miracles or about magic?
See also: What is Life? (1944)


Indeed, in the case of higher animals we know the kind of orderliness they feed upon well enough, viz. the extremely well-ordered state of matter in more or less complicated organic compounds, which serve them as foodstuffs. After utilizing it they return it in a very much degraded form -not entirely degraded, however, for plants can still make use of it. (These, of course, have their most power supply of ‘negative entropy’ the sunlight)

See also: What is Life?: The Intellectual Pertinence of Erwin Schrödinger with a forward by Roger Penrose

How often do we still hear that quantum effects can have little relevance in the study of biology, or even that we eat food in order to gain energy?

My comment: Is life supported by “magical enhancer” elements, or by photosynthesis and nutrition in accord with Schrodinger, Penrose, and Darwin’s nutrient-dependent “conditions of life?” Darwin’s “conditions of life” also are controlled by the energy-dependent physiology of reproduction.

Will debate over the facts that link angstroms to ecosystems via energy-dependent changes in hydrogen-atom transfer in DNA base pairs in solution lead to resolve of any issues invented by pseudoscientists. See, for example: Watch the Great Debate on Connectomics (April 7, 2016 – video)


On one side was Moritz Helmstaedter of the Max Planck Institute, arguing that understanding neuronal circuit structure is key to modeling the mind. On the other side was Anthony Movshon of NYU, arguing that functional models that carefully analyze behavior are the key.

See also: Toward Predicting Personalized Neural Responses (April 7, 2016)


Individual brains differ in shape, architecture, and connectomes, impacting how different parts of the brain communicate. A long-standing question in neurobiology is to what extent brain architecture and/or neural connections underlie behavioral differences observed among people.

My comment: Who is questioning whether the conserved molecular mechanisms of nutrient-dependent pheromone-controlled cell type differentiation extend from C. elegans to the morphological and behavioral differences of P. pacificus (a predatory nematode with teeth) and humans?

What aspect of the biophysically constrained chemistry of RNA-mediated protein folding, which links the innate immune system to supercoiled DNA in all living genera, do pseudoscientists think is questionable?

At a time when all models are supported by experimental evidence of biologically-based cause and effect that links angstroms to ecosystems, who wonders if energy-dependent hydrogen-atom transfer in DNA base pairs in solution links the anti-entropic energy of the sun from the morphological and behavioral phenotypes of microbes to humans?

See also: What is life when it is not protected from virus driven entropy? (6 minute video)

See also:  The science behind bodily secretions (April 5, 2016)

Excerpt: “…all four parts must be activated (turned on) for calcium to increase in a cell and start processes like fluid secretion.”
My comment: The four parts are nutrient-dependent and controlled by the physiology of reproduction, which links RNA-mediated events to transgenerational epigenetic inheritance of cell type differentiation via the biophysically constrained four parts in species from microbes to humans.
All four parts of the biophysically constrained receptor-mediated events involve the sensing and secreting of molecules that allow different cell types and organisms to achieve the versatile social behaviors, which are controlled by the metabolism of nutrients to species-specific pheromones in species from microbes to humans.
See also my comment on:Secreting and Sensing the Same Molecule Allows Cells to Achieve Versatile Social Behaviors

Re: “Evolution appears to favor efficient circuits and signaling elements that can accomplish many different tasks…”
That was inferred in our 1996 Hormones and Behavior review: From Fertilization to Adult Sexual Behavior. We started with the conserved molecular epigenetics of yeasts and extended nutrient-dependent genetic diversity from the metabolism of nutrients to the pheromone-controlled physiology of reproduction in species from microbes to man.
Four years later our yeast-to-mammalian model was extended by others to hormone-organized and hormone-activated invertebrate behavior, and 5 years after that to the life history transitions of the honeybee model organism.
Since then, “Signaling Crosstalk: Integrating Nutrient Availability and Sex” has linked yeasts to “Feedback loops link odor and pheromone signaling with reproduction” in other species and to “Nutrient-dependent/pheromone-controlled adaptive evolution: a model”
Placing all these published works into the context of evolution as Youk and Lim have done seems somewhat problematic for some evolutionary theorists. The conserved molecular mechanisms appear to represent adaptations to ecological variation via nutrient-dependent secretion of pheromones and the sensing of pheromones.
That links the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man.
The fact that ecological adaptations occur via a nutrient-dependent signaling pathway, which regulates a pheromone-controlled signalling pathway shows how unicellular and multicellular organisms produce a coordinated response to multiple stimuli with no consideration for mutations or for natural selection of anything except food.
That does not present a problem in the context of biologically-based food odor- and social odor-driven cause and effect, but it makes mutation-driven evolution appear to be not only biologically implausible but also to not be an ecologically valid approach to species diversity.

See also: Modern men lack Y chromosome genes from Neanderthals, researchers say


…a woman’s immune system might attack a male fetus carrying Neanderthal H-Y genes. If women consistently miscarried male babies carrying Neanderthal Y chromosomes, that would explain its absence in modern humans. So far this is just a hypothesis, but the immune systems of modern women are known to sometimes react to male offspring when there’s genetic incompatibility.

My comment: The innate immune system links ecological variation to ecological adaptation in species from microbes to humans via RNA-mediated events that link amino acid substitutions to supercoiled DNA, which protects all organized genomes from virus-driven energy theft and entropy. Energy theft links mutations to all pathology.

See: Species of Drosophila (1972)
Excerpt 1)

A biological species concept is therefore necessary. Its beginning goes back to John Ray, who stated in 1686 that “one species never springs from the seed of another” [quoted in (1)].

Excerpt 2)

They [species] are separated by any one, or by a combination of several, reproductive isolating mechanisms, (1, 4-7). Hybrid inviability and sterility are among such mechanisms, but there are others (for example, ethological and ecological isolations) which may be just as effective in nature.

My comment: Nutrient-dependent pheromone-controlled cell type differentiation links supercoiled DNA and  chromosomal rearrangements to protection against virus driven entropy in all vertebrates. That is why modern men lack Y chromosome genes from Neanderthals. The experience-dependent de novo creation of olfactory receptor genes links chemotaxis and phototaxis to other sensory input and to behavior via supercoiled DNA, which protects organized genomes from virus-driven entropy.
See also: Natural Selection on the Olfactory Receptor Gene Family in Humans and Chimpanzees (2003) — co-authored by Carlos D. Bustamante

…humans may identify the selected changes and shed light on what olfactory stimuli have exercised selective pressures on the human OR gene repertoire.

My comment: Food odors and pheromones exercise selective pressure that enable the olfactory receptor gene repertoire, which links supercoiled DNA to protection against virus-driven entropy in the organized genomes of all living genera. As it always has been, supercoiled DNA is the link from metabolic networks to genetic networks that typically prevents hybridization. By preventing hybridization, food odors and pheromones establish the niche construction that is exemplified in every species.
See also:  The Divergence of Neandertal and Modern Human Y Chromosomes (2016) — co-authored by Carlos D. Bustamante
My comment: Scientific progress has led all serious scientists to explanations that link angstroms to ecosystems in all living genera. Serious scientists have linked what is known about molecular diagnostics across all species. When will neo-Darwinian theorists admit that they have known how odors and pheromones link biophysically constrained RNA-mediated cell type differentiation to supercoiled DNA in all living genera?
Obviously, not all theorists are committed to telling “Just So” stories about mutations and human evolution. For example, see: Clustered mutations in hominid genome evolution are consistent with APOBEC3G enzymatic activity, which was reported as: Human evolution fast-tracked by mutations from anti-viral enzyme
Excerpt (with my emphasis):

…when examining the locations of the clustered mutations, the researchers found they were enriched in transcriptionally active and regulatory regions of the human genome. Over a third of mutations overlapping coding regions led to amino acid changes, and in several cases an entire mutation cluster overlapped, resulting in up to five amino acid substitutions in a single exon.
Our results are at odds with assumptions of mutational models that are at the basis of most genetic analyses, including in medical genetics, evolutionary genetics, and population genetics,” co-corresponding author Keinan said.

My comment: Those assumptions were based on de Vries 1904 definition of mutation.  [W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. 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…. Assumptions, made but not verified, were taught as fact.
The facts have since been repeatedly stated and often succinctly stated, as in:  Feedback loops link odor and pheromone signaling with reproduction; and in Combating Evolution to Fight Disease and in MicroRNA-Based Single-Gene Circuits Buffer Protein Synthesis Rates against Perturbations. 
In my invited review of nutritional epigenetics I placed the facts into the context of nutrient-dependent pheromone-controlled biophysically constrained cell type differentiation and changes in the microRNA/messenger RNA balance, which are linked from RNA-mediated amino acid substitutions to cell type differentiation in all living genera.
See: Nutrient-dependent pheromone-controlled ecological adaptations: from atoms to ecosystems (April 11, 2014)
Abstract excerpt:

This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding; experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man.

My comment: My invited review was promptly returned without review.

For comparison, see this award-winning invited review: The Mind’s Eyes: Human pheromones, neuroscience, and male sexual preferences

In his review of my award-winning review, David A. Puts wrote:

James Kohl authors the Handbook’s final chapter, “The mind’s eyes: Human pheromones, neuroscience, and male sexual preferences.” Kohl posits innate sex differences in preferences for sexually dimorphic pheromones. These sex pheromones act as unconditioned stimuli that become associated with visual and tactile stimuli through classical conditioning. Consequently, men with innate preferences for women’s odors come to prefer the appearance and feel of women, for example. Homosexuality results from incomplete sexual differentiation of the olfactory system.

Kohl marshals supporting evidence, though it is often subject to alternative interpretation. For example, Kohl suggests that exposure to sex pheromones is “the most likely explanation for the recent finding that saliva [testosterone] levels in men increase with exposure to a young woman, but do not increase with exposure to a young man” (p. 327). Is it not likely that the young woman’s appearance raised men’s testosterone levels?

Multiple studies by independent researchers leave little doubt that odor affects human mate choice, but Kohl probably grossly overstates its importance. Why postulate that humans evolved only obligate olfactory/pheromonal preferences? Isn’t there likely to be useful information about mates that is better obtained through vision and touch than through smell? If so, selection would probably favor more reliable developmental patterns for visual and tactile preferences than classical conditioning to olfactory ones. Moreover, there is a trend among anthropoid primates, including humans, for reduced olfaction and increased reliance on vision for locating food and mates. This is witnessed in our tiny olfactory bulbs, which are relatively many times smaller than in rats; and our apparent lack of a functional vomeronasal organ, which is used by many mammals to detect pheromones.

Ironically, a seemingly fatal blow follows from a condition that Kohl presents in support of his hypothesis. Prior to treatment, people with Kallmann Syndrome (KS) lack both a sense of smell and much of a libido. Superficially, these facts appear to support Kohl’s hypothesis that olfaction is primary in sexual interest. However, the relation between olfaction and libido here is not causal. In most fetuses, some cells in the olfactory placode develop into olfactory cells while others migrate to the hypothalamus to become cells that trigger sex hormone secretion by the gonads. A mutation in one of three known genes can disrupt the development of these cells, so that a person not only lacks a sense of smell but also has gonads that do not produce sex hormones. It is the low sex hormone levels, rather than a lack of olfaction, that leads to reduced libido in adults with KS: Testosterone treatment at least partially restores libido in men with KS, but there is no known treatment for their anosmia.

My comment: David A. Puts is one of the most personable and intelligent antagonists I have ever met, but he failed to realize that I was not detailing a hypothesis. The model I detailed has been supported by all experimental evidence of biologically-based cause and effect since the time I first presented it in 1992, and subsequently co-authored The Scent of Eros: Mysteries of Odor in Human Sexuality (1995/2002).

See also: On April 9, 2016 at 1145 AM, on the sexnet listserver, David A. Puts, PhD (Associate Professor, Department of Anthropology, Center for Brain, Behavior, and Cognition, Center for Human Evolution and Diversity, Penn State University, University Park, PA 16802, wrote:

“Modern humans may also have abducted Neandertal females, so that the flow of Neandertal genes into modern human populations was primarily through females. Hypergynous marriage along the lines that Ray describes is also a possibility, but my gut is that relations between “us” and “them” weren’t so civil.
A less sexy possibility that the authors mention is simply that the Neandertal Y was lost due to drift. (The effective population size of Y chromosomes is half that of autosomes, and drift is stronger in smaller populations.)
Gene flow primarily through females and loss of Neandertal Y’s through drift are not mutually exclusive, but drift seems more consistent with also losing Neandertal mtDNA.

And of course there could be selection against the Neandertal Y in human-Neandertal hybrids, as the authors suggest.”

My comment: None of his claims are supported by experimental evidence of biophysically constrained biodiversity in any species.
For comparison, see: Formation of novel PRDM9 allele by indel events as possible trigger for tarsier-anthropoid split
Abstract excerpt:

The first mutation event interrupts the reading frame and function while the second compensates both. The fixation of this peculiar allele variant in tarsiers led to hypothesize that de- and reactivation of the zinc finger domain drove the speciation in early haplorhine primates.

My comment: Only if you believe that mutations are fixed in organized genomes can you link virus-driven energy theft from pathology to neo-Darwinian pseudoscientific nonsense in which alleles are somehow formed outside the context of the nutrient-dependent physiology of reproduction. Only if you believe that mutations are fixed in organized genomes can you link weekend evolution of the bacterial flagellum from mutations the evolution of primates. But as all serious scientists know, those who link mutations to the evolution of microbes into primates never learned the difference between mutations and nutrient-dependent RNA-mediated amino acid substitutions that link de novo gene creation to biodiversity in the context of the innate immune system and supercoiled DNA.


A two-faced protein enables RNA-mediated DNA repair (3)

See: A two-faced protein enables RNA-mediated DNA repair (2)
See: A two-faced protein enables RNA-mediated DNA repair
My comment: Attempts to place what is currently known about the links from atoms to ecosystems back into the context of neo-Darwinian pseudoscientific nonsense have been doomed to fail ever since Dobzhansky (1973) wrote: Nothing in Biology Makes Any Sense Except in the Light of Evolution.
He linked nutrient-dependent amino acid substitutions to cell type differentiation across species and also claimed

“…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla (p. 127).”

Others have since continued to reveal the reasons for the similarities and the differences in cell types that vary in the context of the fixation of these amino acid substitutions in organized genomes via the physiology of reproduction in all living genera. Indeed, it has become obvious that The pronoun ‘I’ is becoming obsolete.
The facts about symbiosis scare all evolutionary theorists because they know those facts cannot be placed into the context of their ridiculous theories. Still, they must try.
See:  Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes

…there is no fundamental rewriting of Darwin’s and Wallace’s theory of evolutionary biology involved in this concept. Like single nucleotide mutations, acquisition of new symbionts births raw genetic variation that evolution can operate on.

My comment: If you asked any theorist to explain how new symbionts are somehow acquired, or what level of importance they attribute to the automagical acquisition, they might claim that it fully supports the pseudoscientific nonsense of their ridiculous theories about increasing organismal complexity, which link beneficial mutations to evolution of new species. However, no experimental evidence of biologically-based cause and effect supports such ridiculous misrepresentations.
For comparison, see: Hidden Diversity in Honey Bee Gut Symbionts Detected by Single-Cell Genomics
and Experimental replacement of an obligate insect symbiont,
which was
Reported as: What’s mine is yours, and what’s yours is mine

Evidence of success came when not just the symbionts but also the recipient aphids developed a striking tolerance to high temperatures.

My comment: Three articles published on the same page of the same issue of DDNews address all current experimental evidence that is linked from protein biosynthesis and degradation to organism-level thermoregulation.
A shock to the system?

Small heat shock proteins are a type of protein that are constantly present, but are highly expressed when cells are exposed to stressful conditions and function as “catastrophe aid workers.”

The mediation of mTORC1

…David M. Sabatini, M.D., Ph.D., published groundbreaking research describing, for the first time, the identification and characterization of the cellular proteins responsible for sensing and mediating the metabolic effects of the amino acid leucine. The paper, published October 8 online in the journal Science, elucidates a key regulatory node related to leucine that was previously unknown within the multiple steps of the mTORC1 activation pathway. The anabolic amino acid, leucine, is critical in cellular protein and lipid synthesis and directly regulates mammalian physiology including skeletal muscle growth, insulin secretion and food intake.

Sifting through the genome

…we know that 90 percent of associated variants found in GWAS are outside of the protein-coding areas,” Pazin adds. “Eventually, we want to understand mechanistically how the variants function in regulating genes, and how differences in the way they function affect disease risk.”

My comment: Disease risk and predictable responses to treatments are RNA-mediated.

For more information about the difference between healthy longevity and pathology, listen to this podcast: Panel Discussion: How Can Life Extension Become as Popular as the War on Cancer?
My comment: The popularity of theories largely depends on funding.  For example, funding for the evolution industry has helped to support the “War on Cancer” because the ridiculous theories of pseudoscientists link beneficial mutations to evolution. Those ridiculous claims have led to millions of wasted dollars and wasted efforts by pseudoscientists who tried to find a difference between beneficial mutations and the mutations linked to pathology. All mutations eventually will be linked to pathology via the replication of viruses that causes all pathology.
Why do you think this researcher appears to be somewhat angry as he explains the link from metabolic networks to genetic networks in the context of healthy longevity via nutrient-dependent microRNAs linked from cell adhesion molecules to supercoiled DNA, which protects organized genomes from heat shock linked to pathology in the context of virus-driven entropy?

A theorist’s answer to any accurate representation of biologically-based cause and effect linked to healthy longevity or to pathology will always be something like this, which is posed as a question.
Was early animal evolution co-operative?

In their new ‘savannah’ hypothesis, they propose that concentration of nutrients both above and below the sediment-water interface were enhanced around the stationary Ediacarans, and the creation of these resource “hot spots” created a very diverse environment, ideal for both diversification and for investment of energy into movement. Rather than the Ediacarans and later animals being direct competitors then, the Ediacarans themselves created a permissive environment that was ideal for higher animals to evolve in. This idea fits well into a modern view of evolution, called “ecosytem engineering” whereby key species (such as beavers) influence the environment in order to create new evolutionary and diversity opportunities for other species. Perhaps then, the Ediacaran taxa weren’t impediments but the drivers of the evolution that was eventually to lead to all the rich animal diversity we see today.

My comment: What evolved? How? Ridiculous questions that start with assumptions about animal evolution in the context of the creation of “hot spots” that created diverse environments are not likely to be considered by serious scientists. Those who are creationists will claim that the theorists are starting with the de novo creation of energy-dependent differences and all serious scientists who understand what is known about cell type differentiation will link their creationist arguments from atoms to ecosystems via nutrient-dependent adaptations and the physiology of reproduction in all living genera.
Questions about what evolved and how have been asked and answered by all serious scientists since Dobzhansky (1964) complained that:

The notion has gained some currency that 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! I have heard a man whose official title happens to be Professor of Zoology declare to an assembly of his colleagues that “a good man cannot teach zoology. A good man can teach, of course, only molecular biology.

My comment: For example, here’s the answer to the question about what evolved. NOTHING! And, here’s the answer to how anything evolves via beneficial mutations: IT CAN’T!

Here are more details that will help other serious scientists answer questions about energy-dependent cell type differentiation in the context of ridiculous theories.
The Hologenome Concept: Helpful or Hollow?

We argue that the wrong approach is to start with the assumption that associated organisms have evolved to function as a cooperative unit and that the task is simply to characterize mutually beneficial adaptations. This assumption is often incorrect, and embracing it uncritically will slow progress. A more parsimonious approach is to adopt the null hypothesis that interacting lineages have not evolved exceptional hologenome-selected traits, and to test specific hypotheses regarding such traits.

My comment: As a reminder of what all serious scientists have known about assumptions for at least two decades, see this claim from Lynn Margolis via Suzan Mazur.

[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. 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…. Assumptions, made but not verified, were taught as fact.

See also:  Incorporating significant amino acid pairs and protein domains to predict RNA splicing-related proteins with functional roles

Abstract excerpt:

Alternative splicing, which is an important post-transcriptional regulation in eukaryotes, gives rise to multiple mature mRNA isoforms, which encodes proteins with functional diversities. However, the regulation of RNA splicing is not yet fully elucidated…

My comment: Precisely one year after I published my most recent review, which linked RNA-mediated events from amino acid substitutions to cell type differentiation with examples from different species, Jay R. Feierman eliminated me from participation on the International Society for Human Ethology’s human-ethology yahoo group.
Feierman wrote: 

I’m not going to post more from Kohl until he answers the very direct and simple question posed to him by anon, which is whether he (Kohl) believes that RNA splicing can change DNA.

My comment: Knowing that the regulation of RNA splicing was not yet fully elucidated, Feierman had previously commented:

“[MODERATOR NOTE: I don’t believe that Jim Kohl has addressed the very specific question asked of him by anon, which is whether he (Jim Kohl) believes that RNA splicing makes new genes. A simple agree or don’t agree is needed to make the interactions in this thread worth posting.”]

My comment: Feierman effectively reduced all of the levels of biological complexity involved in cell type differentiation in species from microbes to man to an “agree or don’t agree” comment based on what an anonymous participant had proclaimed I was implying.
That anonymous participant was Andrew Jones, who never mentioned that he had written a letter to the editor of Socioaffective Neuroscience & Psychology​. The editor published his criticisms of my model.
Anyone interested in the pseudoscientic nonsense touted by evolutionary theorists and human ethologists will enjoy reading the criticisms of my model by Andrew Jones (aka anonymous_9001).
See:  Criticisms of the nutrient-dependent pheromone-controlled evolutionary model
See the editor’s response:

The 2013 review article by James Vaughn Kohl published in Socioaffective Neuroscience & Psychology and criticized in the above Letter to the Editor was subjected to standard peer review and the revised version was accepted by me after it had been accepted by both reviewers.

My comment: The criticisms show how people like Andrew Jones and people like Jay R. Feierman have managed to continue to convince others that “Random mutations are the substrate upon which directional natural selection acts” is a correct and true statement.” See for example, Jones’ thesis on mutagenesis: Lipid Encapsulation of Self Replicating Ribozymes

Despite their challenges, ribozymes have made an interesting niche for themselves in the field of abiogenesis. The evolution of a successful RNA polymerase ribozyme is a lofty goal. While its discovery would not be the be-all and end-all of abiogenesis research, it would represent an important stepping stone between prebiotic chemistry and life. The encapsulation of such a ribozyme is also an important step, as it would enable a system of heredity and evolution through natural selection. Based on progress in current research, it is only a matter of time before that ribozyme is discovered.

My comment: That statement, and Feierman’s claim about random mutations are based on a ridiculous theory. The claims ignore the accumulation of biological facts that link nutrient-dependent RNA-mediated amino acid substitutions to the differentiation of all cell types in all individuals of all species from microbes to man via conserved molecular mechanisms that obviously involve alternative splicings of pre-mRNA. We placed the alternative splicings into the context of the pheromone-controlled sexual differentiation of cell types in our 1996 Hormones and Behavior review. From Fertilization to Adult Sexual Behavior

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: More than 45,000 publications now link nutrient-dependent microRNAs from cell adhesion proteins to supercoiled DNA and the stability of organized genomes in all living genera via alternative splicings and RNA-mediated events that link the pre-mRNAs / microRNAs to nutrient energy-dependent cell type differentiation.
With three blog posts on the same topic of the two-faced protein that enables RNA-mediated DNA repair,  I continue to repeat myself each time new experimental evidence of biologically-based cause and effect support the claims in the book I co-authored in 1995 with an update in 2002.
For comparison, others need only explain away differences in cell types by claiming links between mutations and their transcriptional history.
See: Somatic mutation in single human neurons tracks developmental and transcriptional history
Excerpt: We also observed a signature of methylated cytosine (meC) to thymine (T) transitions (fig. S8), which can occur as a result of replication-independent deamination of meC, in single-neuron SNVs.
My comment: Having observed such an obvious link from RNA-directed DNA methylation to cell type differentiation, why was the lack of differentiation that links mutations to the transciptional history of undifferentiated cell types in the brain also reported in the context of neo-Darwinian nonsense? What about the missing heritability that links cell type differentiation in C. elegans and P. pacificus from their nutrient-dependent pheromone-controlled physiology of reproduction to differences in their morphological and behavioral phenotypes?
See: System-wide Rewiring Underlies Behavioral Differences in Predatory and Bacterial-Feeding Nematodes