Beneficial epistatic mutations revisited

Lost in Transition: Startup of Glycolysis Yields Subpopulations of Nongrowing Cells 

They looked at the idea of mutation-initiated natural selection in yeasts and found “…that cell fate can be determined by heterogeneity purely at the metabolic level [differences in metabolism].”

My comment: Although all cells that become different cell types may be created equal, even genetically similar cells quickly begin to differentiate when exposed to even the slightest differences in their epigenetic landscape.

Nutrient-uptake varies at the atomic level with differences in exposure to metal ions, vitamins, and minerals, which link amino acid substitutions to what is currently known about biophysical constraints on mutations that perturb protein folding. Perturbed protein folding may not cause the death of a cell, but mutation-caused perturbations are not beneficial to cell survival. See my first blog post on Beneficial epistatic mutations.

Cell fate determined by differences in metabolism also contrasts with Experiments on the role of deleterious mutations as stepping stones in adaptive evolution. The contrast is remarkable, especially in the context of another article that refutes mutation-driven evolution in bacteria.

See for example: Real-Time Evolution of New Genes by Innovation, Amplification, and Divergence. In October 2012, an international team of scientists 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. 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 de novo creation of genes is attributed to mutations as it has always been in reports from Lenski’s group and others. The question arises: Did the different genes mutate and evolve, or were they created by ecological adaptation? I addressed that question less than a month ago in Creation of genes: The holy grail of evolutionary biology

Lost in Transition: Startup of Glycolysis Yields Subpopulations of Nongrowing Cells is yet one more article in a series of articles that use experimental evidence to refute the idea of mutation-initiated natural selection and replace it with a model of nutrient-dependent pheromone-controlled ecological adaptations.

However, the refutations are not accepted. Earlier today, for example, my response to comments made about the obvious refutations of mutations theory was refused. I wrote:

Mutation-driven evolution has no biological plausibility or ecological validity because the availability of nutrients enables ecological adaptations. Also the theory of mutation-driven evolution is not compatible with what is currently known about the physiology of reproduction. Thus, “If you learnt evolutionary biology and genetics a decade or more ago you need to be aware that those debates have moved on very considerably, as has the experimental and field work on which they are based.”

Clarification: I insist that mutations are never beneficial. I do not insist that mutations are always deleterious. If you insist that mutations may be beneficial, support your insistence with experimental evidence (i.e., not mathematical models).

Others have inferred that: On rare occasions mutations confer adaptive advantages, and then those genes are more likely to spread through a population.

Clarification: No experimental evidence suggests that mutations are fixed in the DNA of any organized genome in any species. Others equate mathematical models with experimental evidence of cause and effect.

I agree with the president of the International Union for Physiological Sciences: “…debates have moved on very considerably, as has the experimental and field work on which they are based.” Clearly, Physiology is rocking the foundations of evolutionary biology, and mutation-initiated natural selection or any other theory that involves mutation-driven evolution was tossed over the side of the boat that we started rocking in the molecular epigenetics section of our 1996 Hormones and Behavior review: From Fertilization to Adult Sexual Behavior.

As you may already know, Donna Maney’s group just reported on the systems biology that links vertebrate-wide epistasis to the conserved molecular mechanisms of nutrient-dependent pheromone-controlled alternative splicings of pre-mRNA, amino acid substitutions, and chromosomal rearrangements that lead to different morphological and behavioral phenotypes in sparrows sans mutations. See: Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes.

Ryszard Maleszka’s group just published Epigenomics and the concept of degeneracy in biological systems, which reestablishes the invertebrate to vertebrate connection that Elekonich and Robinson made via incorporation of what we detailed about the molecular epigenetics of hormone-organized and hormone-activated behavior in mammals (e.g., starting with sex differences in yeasts).

The problem for some people may be that experimental evidence of epigenetic cause and effect has ended any debate about mutation-driven evolution because there was never an experimental evidence that supported the theory. If that biological fact is not clear, the problem may be that some people don’t want it to be clear. What they may want is to continue believing in mutation-initiated natural selection instead of learning about how ecological variation results in adaptations via ecological, social, neurogenic, and socio-cognitive niche construction. The non-random experience-driven niche construction is obviously manifested in increased organismal complexity in species from microbes to man with no involvement whatsoever of mutations.

No experimental evidence suggests that the ideas of Fisher, Wright, and Haldane were right, which is why Denis Noble and others have continued to address what’s wrong with Neo-Darwinism/the Modern Synthesis. For example, no experiment attempted to prove Haldane’s idea was right until last year. It proved Haldane was wrong by showing that mutations are not fixed in the genome of C. elegans, after I showed in Kohl (2013) that a nutrient-dependent pheromone-controlled amino acid substitution differentiated the morphology and behavior of a grazing and a predatory nematode.

Although there are other experiments that prove mutation-initiated natural selection is the wrong idea at the atomic level that links physics to intercellular signaling and non-random de novo creation of genes, this is the most recent article from Science to refute what virtually all evolutionary theorists think are the experiments (of Lenski and others) that attest to mutation-driven evolution: Lost in Transition: Startup of Glycolysis Yields Subpopulations of Nongrowing Cells

” Our results reveal dynamic behavior of glycolysis and indicate that cell fate can be determined by heterogeneity purely at the metabolic level.”

Mutations are biophysically constrained (at the atomic level involving sodium ions and cell permeability). The sickle cell allele represents an adaptation to a pathogen, which shows up as one of the other 1181 hemoglobinopathies associated with ecological variations. Dobzhansky (1964) noted that “Ingram and others found that hemoglobin S differs from A in the substitution of just a single amino acid, valine in place of glutamic acid in the beta chain of the hemoglobin molecule.”

What Maney’s group and Maleszka’s group just confirmed was that the ecologically-driven change in a single base pair can lead to a single amino acid substitution and morphological and behavioral differences that are obviously due to chromosomal rearrangements sans mutations. Clearly, their is no reason to attempt to disprove the well-accepted ideas of Fisher, Wright, and Haldane. No one proved their ideas were right.

What others have since proved is that those ideas were simple-minded, which is what usually is proved by experimental evidence as the experiments include new technology.