Creation of genes: The holy grail of evolutionary biology


“Deciphering the genetic mechanisms that operated during the past 650 Myr of animal evolution to create the seemingly infinite variety of animals that populate our planet has been one of the holy grails in biology.” The question arises: “How did evolution create anything?

In October 2012, an international team of scientists attempted to answer that question. They induced a nutrient-dependent gene duplication and forced the two genes to differentiate via nutrient-dependent amino acid substitutions. Simply put, they used ecological variation to create new genes in a living organism. They reported their results in the context of “Real-Time Evolution of New Genes by Innovation, Amplification, and Divergence” Their results exemplify how naturally occurring ecological adaptations result in nutrient-dependent gene duplication. Gene duplication results in the creation of different cell types via nutrient-dependent amino acid substitutions. The question arises: Did the different genes evolve, or were they created by ecological adaptation?

In 1996, we reviewed what was known about the molecular mechanisms of ecological adaptation and nutrient-dependent sexual differentiation of cell types. In our review:  ‘From fertilization to adult sexual behavior,’ we linked molecular epigenetics and the alternative splicings of pre-messenger RNA (pre-mRNA) to the nutrient-dependent creation of new genes and to sex differences in the cell types of yeasts. We also opened the door to discussion about how nutrient-dependent pheromone-controlled divergence of species occurs via sexual reproduction in species from microbes to man. It seemed obvious that the epigenetic effects of food and the metabolism of nutrients to species-specific pheromones controled the physiology of reproduction.

The ability of one epigenetically-effected nutrient-dependent signaling pathway to regulate a second signaling pathway that epigenetically controls the physiology of reproduction exemplifies how different cell types integrate multiple stimuli to produce a coordinated response that enables them to adapt to changes in their ecological niche. First, the availability of nutrients determines ecological niche construction. Subsequently, pheromones control social niche construction. Species-specific pheromones then maintain the epistasis of the ecological niche and the social niche. Nutrient-dependent pheromone-controlled adaptations to the available food supply help to prevent different cell types from exhausting their food supply by reproducing too quickly or for too long.

Biophysical constraints on ecological adaptation:

Nutrient-dependent pheromone-controlled epistasis is typically acheived because nutrient uptake is biophysically constrained by the induction of receptors in the cell membrane of microbes . Ecological variation controls niche construction via the de novo creation of olfactory receptor genes (ORGs). Experience-dependent receptor induction can be considered in the context of (ORGs).

Nutrient-dependent gene duplication and amino acid substitutions enable the de novo creation of olfactory receptor genes (ORGs) that link the epigenetic landscape to the physical landscape of DNA via the epistatically-controlled organization of genomes in species from microbes to man via niche construction.

After the de novo creation of ORGs in insect species, “…ORs are more tightly linked to sensory specialization and adaptation to specific ecological niches and a shared space of semiochemicals.”  Adaptations that involve semiochemicals, which are commonly called pheromones, represent the continuum of nutrient-dependent pheromone-controlled ecological adaptations in unicellular organisms. Ecological adaptations enable nutrients to enter cells. The metabolism of the nutrients to species-specific pheromones controls nutrient-dependent ecological niche construction, social niche construction, and neurogenic niche construction. In my model, increasing nutrient-dependent and pheromone-controlled organismal complexity enables invertebrate and vertebrate socio-cognitive niche construction.

Several researchers have repeatedly inferred that the de novo creation of ORGs, which enables ecological, social, neurogenic, and socio-cognitive niche construction in my model, should be ignored. Others may now be more willing to consider biological facts, if only  because they want to divorce themselves from the claim by one of the human pheromone-deniers that pedophilia may be a deep-rooted, unchangeable predisposition.

Is pedophilia comparable to homosexuality?

The real issue has become the fact that the conserved molecular mechanisms of biophysically constrained ecological adaptations present a problem for anyone who does not understand the difference between a mutated gene and the nutrient-dependent de novo creation of genes. For example, the de novo creation of human ORGs presents a problem for anyone who has meaningfully interpreted meaningless results from their experiments because they did not consider one of the holy grails of evolutionary biology. Sexually dimorphic species-specific pheromones are produced in organisms that have achieved nutrient-dependent reproductive maturation.  It is the nutrient-dependent pheromone-controlled de novo creation of genes that differentiates cell types, individuals, and species via amino acid substitutions in reproductively fit males and females.

Exemplifying de novo gene creation in species from microbes to man means that interpretations of brain imagery can no longer be placed into the context of evolutionary biology and the development of sexual preferences. Instead, what is known about  ecological variation links it directly to nutrient-dependent pheromone-controlled alternative splicings of pre-mRNA via amino acid substitutions and the de novo creation of ORGs and the de novo creation of other genes that are responsible for 1) differences in cell types, 2) differences in individuals, and 3) differences in species.  These differences do not show up in the brain until after increasing organismal complexity has already linked the nutrient-dependent pheromone-controlled neurogenic niche construction in nematodes from differences in their diet to an amino acid substitution and differences in the morphology and behavior of adults.

Immature males and females are not naturally selected for reproduction

Serious scientists must now address what they thought might be caused by evolution and natural selection in adults, since there has never been any evidence to indicate that mutations are fixed in nematodes, or in any other species. For example, instead of attributing any aspect of natural selection to mutated adult morphology and visual input, attributions must be made in the context of 1) the biophysical constraints on mutations; 2) the required link from physics to chemistry; and 3) the conserved molecular mechanisms that enable nutrient-dependent pheromone-controlled ecological adaptations.

Simply put, serious scientists must now address the biological facts we detailed in our 1996 review article. Since then, everything that has been learned about molecular epigenetics in the context of sex determination, sexual orientation, and sexually dimorphic behaviors in the adults of species from yeasts to non-human primates attests to the discovery of one of the holy grails in biology: Creation of genes via alternative splicings and amino acid substitutions.

We (TB) wrote:”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…”  If any serious scientists still think that genetically predisposed sex differences in human behavior result from something besides ecological variation and de novo gene creation, they need to provide experimental evidence to show others how sex differences could arise in every species on this planet via mutations, natural selection, or anything else.

Nothing about evolutionary theory makes sense except in the light of biology

Some people may still believe what they have been told about mutation-driven evolution. Others may believe what they have been told about what brain imaging shows. Clearly, brain imaging in adults shows us nothing about natural selection, and nothing about how differences in hormone levels or other measures result in the development of sexual preferences develop associated with responses to visual input. Fifty years ago, Dobzhansky (1964) mentioned people who believe in what they visually perceive. He said: “…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 am not qualified to determine whether Dobzhansky was too harsh. However, I have been a medical laboratory scientist for 40 years, and I own the domain, which is where more than 800 seriously scientific blog posts can be found that attest to what is currently known about biologically-based cause and effect that starts with the de novo creation of genes.

Some people claim that I should be ignored because I have commercial interests in the sale of human pheromone-enhanced fragrance products. I compare my commercial interests to the interests of academics who must acquire government funding for their studies. During the past 40 years of my career, and the 50 years since Dobzhansky (1964), the study results of academics have not led to any model of anything that can be compared to what is currently known about the biological basis of behavior in all species.

The biological basis of behavior  in all species is nutrient-dependent and pheromone-controlled. It is not mutation-initiated and naturally selected. The biological basis of behavior depends on the natural selection of nutrients and ecological adaptations.

In my model, our socio-cognitive niche construction and our behaviors are directly linked from ecological variation via the epigenetic effects of olfactory/pheromonal input on hormone-organized and hormone-activated invertebrate and vertebrate behaviors. For an example in the context of de novo gene creation see Kohl (2012):

“A gene that codes for the mammalian olfactory receptor, OR7D4, links food odors to human hunger, dietary restraint, and adiposity (Choquette et al., 2012). OR7D4 exemplifies a direct link1 from human social odors to their perception (Keller, Zhuang, Chi, Vosshall, & Matsunami, 2007) and to unconscious affects2 on human behavior associated with human olfactory-visual integration (Zhou, Hou, Zhou, & Chen, 2011); human brain activation associated with sexual preferences (Savic, Heden-Blomqvist, & Berglund, 2009), human learned odor hedonics; and motor function (Boulkroune, Wang, March, Walker, & Jacob, 2007). Insect species exemplify one starting point along an evolutionary continuum from microbes to humans that epigenetically links food odors and social odors to multisensory integration and behavior.”

I start with the nutrient-dependent de novo creation of ORGs in insects and link ecological adaptations in other species to the de novo creation of cell membrane receptors in yeasts. Those receptors enable nutrient-dependent pheromone-controlled ecological adaptations at the origin of sex differences in cell types and the origin of sexual reproduction.

Simply put, from the discovery of one of the holy grails or biology: Creation of genes, my model uses what is currently known about molecular epigenetics in an accurate representation of how nutrient-dependent pheromone-controlled differences in cell types lead to Mosaic Copy Number Variation in Human Neurons.


My accurate representation of biologically based cause and effect can be compared to the conclusion reached at the end of the article that noted how important it was for someone to decipher  “…the genetic mechanisms that operated during the past 650 Myr…”

‘The articles, reviews and perspectives that follow this introduction shed more light in the still murky and mysterious world of gene expression evolution in the animal kingdom. Each of these papers, in one way or another, consolidates the idea that there will probably be no fixed law, like gravity, to explain at the molecular level how endless forms most beautiful and most wonderful have been, and are being evolved. It rather seems that a wide variety of peculiar molecular mechanisms perform, together, the complex task of putting the genome in action, in each cell type of each animal species, at every moment in life and under every possible physiological and environmental circumstance.

Nutrient-dependent pheromone-controlled de novo gene creation of olfactory receptor genes is not a peculiar molecular mechanism; it represents the conserved molecular mechanisms that link the sensory environment directly to behavior via ecological adaptations. It seems to me that nutrient-dependent pheromone-controlled ecological adaptations are clearly responsible for alternative splicings and the amino acid substitutions that exemplify variations in each cell type; in every tissue; in every individual; of every species under every possible physiological and environmental circumstance. It seems equally obvious to me that no experimental evidence has ever suggested anything else.

The question: Is pedophilia a sexual orientation? can be addressed in the same context as the question about whether our brain evolved due to the need for enhanced visual acuity and specificity for snake detection, as was recently proposed in the context of snake-centric theory based on brain imaging in non-human primates. There is no answer to a question like that except when posed as another question: Is there a model for that?

Author: James Kohl

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