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Epistasis as the primary factor in molecular evolution

Posted on January 14, 2013 by James Kohl.

The genetics of molecular evolution (revisited)

Excerpt: “…nucleic acid sequencing allowed molecular evolution to reach beyond proteins to highly conserved ribosomal RNA sequences, the foundation of a reconceptualisation of the early history of life.

My comment: So far as is known, the early history of life includes the genetic predispositions of the first cell, and no evidence suggests that the first cell randomly appeared or automagically “appeared” to contain genes. Thus, physicists or others with theories about our adaptively evolved existence, may want to compare what they know to the biological facts represented below.

Epistasis as the primary factor in molecular evolution provides mathematical evidence for genetic interactions within proteins. These epistatic interactions support the hypothesis that the interaction of cellular components and structural interactions within the same molecule are responsible for the large majority of all amino-acid substitutions. These substitutions may be adaptive or not.

No support is offered for any hypothesis that suggests mutations are adaptive. Instead, it now seems more likely that the epigenetic effects of nutrient chemicals and pheromones on epistasis cause adaptive evolution because calculations attest to the interactions of cellular components and structural interactions within the same molecule.

The mathematical problem inherent to mutation theory or other theories of adaptive evolution is that epistasis is rarely achieved. It does not seem even remotely possible that epistasis could be achieved by one, two, or whatever number of sequential or simultaneously expressed mutations might be required to adaptively evolve a human genome with 4.5 million epistatically controlled DNA switches. Thus, although epigenetic effects on intracellular signaling lead to intramolecular interactions that occur in closely related sequences (e.g., the “mutational vicinity” in the genetic code), there is nothing in this report to suggest that epistatic interactions occur due to mutations.  Similarly, no evidence suggests that epistasis can be achieved via mutations.

It is more likely that the “mutational vicinity” is a misnomer. That molecular vicinity is simply the most likely portion of the molecule to be epigenetically effected by nutrient chemicals and pheromones in attempts to achieve epistasis either at the unicellular level or in the cell types of multicellular organisms. In essence the “mutational vicinity” is probably found in the molecular vicinity of a “metabolite niche” within specific chromatin subdomains.

Indeed, these authors attest — with my emphasis — to the likelihood that “…when the fitness effects of all amino-acid states are independent of one another, substitutions in different species are expected to have similar effects on fitness except in cases where these substitutions enable differences in adaptation to environmental conditions.” Exceptions that enable differences in adaptation to environmental conditions are unequivocally required for species divergence.

The exceptions involve the selection by one species of nutrient chemicals that metabolize to species-specific pheromones, which control nutrient chemical-dependent reproduction in species from microbes to man. If another species selects precisely the same nutrient chemicals to benefit its survival in precisely the same way, the two species are genetically predisposed to fight for survival until one winner clearly emerges, or both species learn to peacefully co-exist. Could the winner have the most adaptively evolved metabolite niche contained within its species specific chromatin subdomains?

Epistasis is acheived via ecological, social, neurogenic, and socio-cognitive niche construction in species (i.e., long-term), but it is not typically achieved in individuals (i.e., short-term). It is the lack of short-term epistasis that enables species divergence via the underlying chemical ecology of niche construction that takes place in the long-term. The long-term construction of the best adapted metabolite niche fits within the context of ecological, social, neurogenic, and socio-cognitive niche construction.

In his monograph: Gene duplication as a mechanism of genomic adaptation to a changing environment, the senior author of the paper on epistasis attests to my representation of the molecular vicinity or “metabolite niche” as one that is epigenetically effected by a nutrient chemical. “A clear example of a gene duplication conferring an adaptive response to nutrient limitation is that of the yeast hexose transporter. Under growth conditions with low glucose, the appearance of a new hybrid copy from two closely related paralogues, HXT6 and HXT7, increases the level of expression of the hexose transporter and, crucially, the rate of glucose transport into the cell [41]. ” – p. 3.

In addition to this attestation about the epigenetic effect of glucose, or lack or glucose, Dr. Fyodor Kondrashov notes that “One of the main duplicated gene families are the olfactory receptor proteins [18,117–119] so perhaps their duplication may lead to an increase in sensitivity to a particular odour [that] may be adaptive under certain conditions.” – p. 5

At the advent of sexual reproduction in yeasts, it is the nutrient chemical-dependent production of the alpha-mating pheromone that enables self / non-self recognition and the exchange of genetic material in yeasts. Similarly, it is the glucose-dependent regulation of gonadotropin releasing hormone neurosecretory neurons that enables mammals to respond to food odors and to respond to the pheromones of conspecifics with adaptively evolved behaviors. When viewed from the perspective of their common molecular biology, the epigenetically-effected behaviors of mammals are no more complex than those of microbes.

Across species comparisons can be made that involve all of the components required for adaptive evolution, which include a metabolite niche but exclude mutations. For example, nutrient chemical-dependent pheromone production, which may be altered by the metabolite niche, is always required and in my model “Olfaction and odor receptors provide a clear evolutionary trail that can be followed from unicellular organisms to insects to humans.





James Kohl
Retired medical laboratory scientist

James Kohl

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