Copy number variations and the new ‘Science’ of mind

Gray Matter The New Science of Mind By ERIC R. KANDEL Published: September 6, 2013

Excerpt: ‘…scientists have recently discovered that some mutations give rise to structural differences in our chromosomes. Such differences are known as copy number variations.”

My comment: Dr. Kandel simply attributes the  copy number variations (CNVs) to mutations. He does not address any aspect of how CNVs are maintained in the genome. Structural differences in our chromosomes are due to mutations, and not to epigenetic effects of sensory input. That may be acceptable to an audience that is only capable of understanding mutation-driven evolution, which has not been modeled in any species.  It is not acceptable to those, like me, who have progressed from theories about mutation-driven evolution to a model of biologically-based cause and effect that includes the nutrient-dependent pheromone-controlled physiology of reproduction in species from microbes to man.

For example, Kondrashov (2005) mentions “…a new model of evolution of new functions through natural selection: new functions can evolve before duplication, after which specialization of duplicate copies may allow for fine-tuning of these functions and independent patterns of expression.” Kondrashov cites The ‘evolvability’ of promiscuous protein functions. This evolvability shows up in significant increases in messenger RNA (mRNA).

In my model, changes in the microRNA (miRNA)/mRNA balance are nutrient-dependent and pheromone-controlled, which explains why the epigenetic effects of nutrients show up as alterations in mRNA. Additional details in my model make it important to note that seven years later, Kondrashov offered an example of nutrient-dependent CNVs in yeast. The example is based on the new model of adaptive evolution through new functions, which are clearly linked to glucose uptake. “…[T]he strain with the gene duplication outcompetes the parental strain.”

In this same yeast species, which is a model organism for much of what is now known about molecular epigenetics, we have the origin of sexual orientation. In 1996, we wrote: “Parenthetically it is interesting to note even the yeast Saccharomyces cerevisiae has a gene-based equivalent of sexual orientation (i.e., a-factor and alpha-factor physiologies). These differences arise from different epigenetic modifications of an otherwise identical MAT locus (Runge and Zakian, 1996; Wu and Haber, 1995).”

In the past, it was probably overly speculative to infer that the epigenetic effects of nutrients on the miRNA/mRNA balance might also be responsible for sex differences in morphology and behavior that were traditionally attributed to genes, like SRY in mammals. But, in the past two weeks, that perspective changed with reports that help to clarify the fact that 1) other factors are responsible for sexual differentiation in mammals, see also 2) Inherited human sex reversal due to impaired nucleocytoplasmic trafficking of SRY defines a male transcriptional threshold. Now, more than one report links nutrient-dependent CNVs, but not mutations, to pheromone-controlled reproduction.

For example, Kondrashov reported that “One of the main duplicated gene families are the olfactory receptor proteins…” Kondrashov (2012) suggests “…their duplication may lead to an increase in sensitivity to a particular odour [which] may be adaptive under certain conditions.”  He cites others who state: “We have, therefore, identified the genetic basis of one response to selection in a glucose-limited environment.” The genetic basis of selection in a glucose-limited environment is found in CNVs linked to glucose uptake, not in CNVs linked to mutations.  If reproduction is nutrient-dependent and pheromone-controlled, Kandel’s misrepresentation of mutation-driven CNVs becomes clear. CNVs are controlled by pheromones that control species-specific nutrient-dependent reproduction.

No doubt others will protest, since I am challenging the representation made by a Nobel Laureate. Fortunately, another Nobel Laureate has also already challenged this misrepresentation by Kandel. See for example, Feedback loops link odor and pheromone signaling with reproduction, which was co-authored by 2004 Nobel Laureate, Linda Buck. Indeed, Kondrashov’s yeast model extends well to mammals via focus on the conserved thermodynamically stable neuropeptide gonadotropin releasing hormone (GnRH).  In yeasts, a form of mammalian GnRH is the alpha mating pheromone, which in concentrated form elicits a luteinizing hormone (LH) response from the cultured pituitary cells of a mammal, the rat. If Kandel, or anyone else, can detail a similar effect on nutrient-dependent pheromone-controlled reproduction in species from microbes to man that can be attributed to mutations and CNVs, he might also make a case for mutation-driven evolution that no one else has made.

Until then, I note that even Darwin, who knew nothing about mutations theory, acknowledged the role of ‘conditions of life.’ It should not take much to convince others that his ‘conditions of life’ are nutrient-dependent and pheromone-controlled via epigenetic effects on CNVs sans mutations. In my model, I exemplify cause and effect in microbes, nematodes, insects, other mammals, and in a human population that adaptively evolved in what is now central China during the past ~30,000 years.  Others need only acknowledge that nutrients cause changes in base pairs that lead to single nucleotide polymorphisms (SNPs) associated with de novo creation of olfactory receptor genes, with organism-level morphogenesis, and with organism level thermoregulation. We can then begin to discuss cause and effect in the context of CNVs that clearly are not due to mutations in any species. For example, two non-synonymous SNPs result in two amino acid substitutions that severly impair function in vitro of the human ability to detect androstenone and androstadienone.