96 fixed amino acid substitutions, not 96 genes

By: James V. Kohl | Published on: January 1, 2014

19 December, 2013 – 09:31 april holloway
Entire Neanderthal genome finally mapped – with amazing results
Excerpt (with my emphasis):
“Only 96 genes responsible for making proteins in cells are different between modern humans and Neanderthals. Intriguingly, some of the gene differences involve ones involved in both immune responses and the development of brain cells in people.”
“Somewhere within these 96 genes may lay the answer to why Neanderthals and Denisovans became extinct.”
Journal article: The complete genome sequence of a Neanderthal from the Altai Mountains
Excerpt (with my emphasis): “This list of simple DNA sequence changes that distinguish modern humans from our nearest extinct relatives… contains only 96 fixed amino acid substitutions in a total of 87 proteins and in the order of three thousand fixed changes that potentially influence gene expression in present-day humans…”
My comment: Cause and effect attributed to 96 genes is different from cause and effect attributed to RNA-mediated 96 fixed amino acid substitutions. I ignore most articles that attribute cause and effect to genes. Serious scientists have known for several decades about interactions between the environment and genes, which result in fixed amino acid substitutions. Details of those interactions have established the fact that ecological variation is responsible for amino acid substitutions in the species-specific genes of DNA.
The epigenetic landscape determines the physical landscape of DNA in the organized genomes of species from microbes to man. Serious scientists must somehow convey that information to science journalists who must learn the difference between a theory of what 96 genes might do and compare that to what 96 fixed amino acid substitutions actually do. For example, the epigenetic effects of olfactory/pheromonal input on  pre-messenger RNA (pre-mRNA) cause alternative splicings that result in amino acid substitutions in genes. These nutrient-dependent pheromone-controlled amino acid substitutions differentiate the cell types of individuals in species.
I’ve detailed this cause and effect relationship in the human influenza virusbacteria, bird plumageaquatic species lineages, and whales. Those details were added after I exemplified the power of amino acid substitutions in the differentiation of cell types in nematodes, insects, other mammals, and humans in a recent review. Epigenetically-effected thermodynamic cycles of protein biosynthesis and degradation result in fixation of amino acid substitutions that stabilize organism-level thermoregulation in the context of ecological adaptations.
Statistical misrepresentations of cause and effect suggest that mutations are fixed in the genome, but no experimental evidence supports that possibility. All experimental evidence shows that mutations perturb protein folding and organism level thermoregulation, which is why mutations that perturb protein folding are typically eliminated from the genome. There are no known beneficial mutations that are fixed in any genes. Mutations may not be removed is they are not harmful, or if the organism’s natural genetic engineering is disabled.
The entirety of the story line that led to claims of beneficial mutations in experiments done on E. coli by Richard Lenski, is an ongoing misinterpretation of results. Nutrient-dependent gene duplication and nutrient-dependent differentiation of cell types occurs via amino acid substitutions. This is what was reported in Real-Time Evolution of New Genes by Innovation, Amplification, and Divergence, but unfortunately the nutrient-dependent duplication and the nutrient-dependent differentiation of cell types via amino acid substitutions were reported in terms of accumulated beneficial mutations and the creation of new genes. Mutations have no creative power. Similarly, even if experimental evidence suggested that natural selection is an evolutionary process initiated by mutation, neither mutations nor natural selection could create a new gene.
However, in The complete genome sequence of a Neanderthal from the Altai Mountains, we have:
1) copy number differences, which are nutrient-dependent: “We find three regions that have been duplicated only on the modern human lineage…”
2) These duplicated and differentiated “… alleles may have contributed to the Denisovan functional variation at the HLA and the CRISP cluster, which are involved in immunity and sperm function, respectively.”
The duplicated genes and differentiated alleles involved in immunity and sperm function help to establish the fact that the amino acid substitutions that differentiate the alleles are nutrient-dependent and pheromone controlled in invertebrates and invertebrates. The conserved molecular mechanisms of nutrient-dependent pheromone-controlled amino acid substitutions are tractable back to sexually differentiated cell types in yeasts. We detailed that fact in the context of molecular epigenetics in our 1996 Hormones and Behavior review: From Fertilization to Adult Sexual Behavior.
In The complete genome sequence of a Neanderthal from the Altai Mountains, the amino acid substitutions are placed into the context of accumulated mutations and inbreeding of Neanderthals and non-African populations via interesting  evidence that suggests gene flow into Denisovans from an unknown hominin. Fortunately, the interesting evidence that suggests gene flow is somehow involved in linking these populations can be compared to physical evidence of nutrient-dependent pheromone-controlled ecological adaptations in the mouse to human model of what happens when a single base pair change results in a single nutrient-dependent amino acid substitution. See for review: Nutrient-dependent/pheromone-controlled adaptive evolution: a model.
“Two additional recent reports link substitution of the amino acid alanine for the amino acid valine (Grossman et al., 2013) to nutrient-dependent pheromone-controlled adaptive evolution. The alanine substitution for valine does not appear to be under any selection pressure in mice. The cause-and-effect relationship was established in mice by comparing the effects of the alanine, which is under selection pressure in humans, via its substitution for valine in mice (Kamberov et al., 2013).
These two reports (Grossman et al., 2013; Kamberov et al., 2013) tell a new short story of adaptive evolution. The story begins with what was probably a nutrient-dependent variant allele that arose in central China approximately 30,000 years ago. The effect of the allele is adaptive and it is manifested in the context of an effect on sweat, skin, hair, and teeth. In other mammals, like the mouse, the effect on sweat, skin, hair, and teeth is due to an epigenetic effect of nutrients on hormones responsible for the tweaking of immense gene networks that metabolize nutrients to pheromones. The pheromones control the nutrient-dependent hormone-dependent organization and activation of reproductive sexual behavior in mammals such as mice and humans, but also in invertebrates as previously indicated. That means the adaptive evolution of the human population, which is detailed in these two reports, is also likely to be nutrient-dependent and pheromone-controlled, since there is no other model for that.”
If we approach this new story in the context of what is known about the amino acid substitutions and differences in cell types, the 96 amino acid substitutions can be considered in the light of other works previously reported by the co-author Svante Paabo and others. For example, it is apparent that Paabo is aware that MicroRNA-Driven Developmental Remodeling in the Brain Distinguishes Humans from Other Primates, and I just mentioned the single amino acid substitution link from mice to humans. Natural selection for nutrients results in the epigenetic effects of food odors that enable the experience-dependent the de novo creation of olfactory receptor genes with amino acid substitutions that different individuals who have had different experiences with food odor and pheromones. Did Paabo forget what he told us in Natural Selection on the Olfactory Receptor Gene Family in Humans and Chimpanzees?
Perhaps he simply cannot address everything in the context of a model. However, separating the driving force of nutrient-dependent brain remodeling from natural selection of nutrients that cause the de novo creation of olfactory receptor genes may lead others away from the facts that link microRNA-driven developmental remodeling of the brain across species from insects to other mammals, see Kohl (2012):
Excerpt: “…epigenetic changes probably occur across the evolutionary continuum that includes both nutrition-dependent reproduction in unicellular organisms and sexual reproduction in mammals. For example, ingested plant microRNAs influence gene expression across kingdoms (Zhang et al., 2012). In mammals, this epigenetically links what mammals eat to changes in gene expression (McNulty et al., 2011) and to new genes required for the evolutionary development of the mammalian placenta (Lynch, Leclerc, May, & Wagner, 2011) and the human brain (Zhang, Landback, Vibranovski, & Long, 2011).
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.”
My comment: Ecological variation in the availability of food clearly epigenetically effects microRNA-driven ecological, social, neurogenic, and socio-cognitive niche struction, which has been exemplified in invertebrates and vertebrates. Ecological variation causes natural selection for the de novo creation of olfactory receptor genes in all species that have olfactory receptor genes.
The question arises: When did natural selection for food and the epigenetic effects of food odors that results in pheromone-controlled microRNA-driven remodeling in the brain that distinguishes mammalian species via the resultant alternative splicings and amino acid substitutions dissappear from further consideration in the most recent work that Paabo co-authored?  
How did Paabo return us to what he and others have told us in the past in the context of another story about the manifestations of fixed amino acid substitutions associated with gene flow  that somehow show up in the context of inbreeding? I’d like some clarification of three points to come from someone who has already indicated that he has a background in publications that qualifies him to address these facts.
1) The fixed amino acid substitutions must come from somewhere,
2) No evidence suggests they come from mutations
3) All evidence suggests they are nutrient-dependent and pheromone-controlled.
If that’s what Paabo is trying to tell us, it could not be less clear. The lack of clarity is a set-back for anyone attempting to model the epigenetic effects of ecological variation, which clearly refute any ideas about how accumulated mutations might somehow be naturally selected and result in mutation-driven evolution.

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