See also: Magic, Miracle, or Molecular Mechanism?
Obviously, not all theorists are committed to telling “Just So” stories about mutations and human evolution. For example, see: Clustered mutations in hominid genome evolution are consistent with APOBEC3G enzymatic activity, which was reported as: Human evolution fast-tracked by mutations from anti-viral enzyme
Excerpt (with my emphasis):
…when examining the locations of the clustered mutations, the researchers found they were enriched in transcriptionally active and regulatory regions of the human genome. Over a third of mutations overlapping coding regions led to amino acid changes, and in several cases an entire mutation cluster overlapped, resulting in up to five amino acid substitutions in a single exon.
“Our results are at odds with assumptions of mutational models that are at the basis of most genetic analyses, including in medical genetics, evolutionary genetics, and population genetics,” co-corresponding author Keinan said.
My comment: All results that serious scientists report have always been at odds with the assumptions of mutational models. The problem is much bigger than most would like to admit. Simply put, there is no mutational model of human evolution; there are only ridiculous unsupported theories.
For example, see: Mutation-Driven Evolution
…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world. In this view of evolution there is no need of considering teleological elements” (p. 199).
My comment: That is the most ridiculous conclusion I can imagine. He claims that there is no need to consider anything else because what he claims is true.
See for support of Nei’s ridiculous claim: Scientists see mechanism for spontaneous HIV ‘cure’ (Update) (2014)
“If it came across my desk for review, it would get short shrift, to be honest,” University of Nottingham molecular virology professor Jonathan Ball told AFP, insisting the team had provided “no evidence” of a functional cure.
My comment: Jonathan Ball might be one of the reviewers that rejects your next submission because you did not provide evidence for a functional cure for what is known to be virus-driven pathology. That means none of your claims are valid in the context of Nei’s claim and that others like Jonathan Ball will give short shrift to your submission based on Nei’s ridiculous claim.
My November 2014 comment to MedicalXpress:
Amino acid substitutions stabilize organized genomes; mutations perturb protein folding.
How could a mutation lead to an “apparent spontaneous cure” given what is currently known about the biophysical constraints and chemistry of protein folding linked to the conserved molecular mechanisms of cell type differentiation in species from microbes to man?.
No results found for: APOBEC in Volume 20, Issue 9 of Clinical Microbiology and Infection.
[I found] A single amino acid substitution in human APOBEC3G antiretroviral enzyme confers resistance to HIV-1 virion infectivity factor-induced depletion http://www.pnas.org/content/101/15/5652.full
The reporting here suffers from a lack of attention to detail. Who was an author of the paper, what issue of the journal contains the information?
I reiterate: A single amino acid substitution in human APOBEC3G antiretroviral enzyme confers resistance to HIV-1 virion infectivity factor-induced depletion (2004)
My comment: The nutrient-dependent RNA-mediated de novo creation of this antiretroviral enzyme has been reported in the context of a spontaneous HIV cure and in the context of confering resistance to HIV-linked energy theft. The fact that only a single amino acid substitution appears to confer resistance to HIV and may also link the molecular mechanisms of cell type differentiation in all living genera to a cure has received virtually no consideration, despite additional reports that link APOBEC3G to species-specific nutrient-dependent pheromone-controlled healthy longevity in species from microbes to humans.
See also: Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNAs genes
The unexpected finding that tRNAs are disproportionally targeted for mutation by AID compared with APOBEC3G, as are the promoters of other highly structured RNAs (snRNA or snoRNA), and the indication that this difference is not due to motif enrichment at those promoters, brings into focus the potential involvement of the RNA binding properties of the deaminases in promoting targeting.
…the normal cycling of the epigenetic methyl-C mark could contribute to the high mutation rate of regulatory sequences thought to contribute both disease processes (Maurano et al., 2012) and evolutionary novelty (Wittkopp and Kalay, 2012).
My comment: Virus-driven energy theft links mutations to pathology. Nutrient-dependent RNA-mediated DNA repair links energy-dependent changes in angstroms to ecosystems and “novelty” manifested in morphological and behavioral phenotypes. For example, the nutrient-dependent resurrection of the bacterial flagellum occurs over the weekend in the context of the physiology of reproduction.
See also: APOBEC3A and APOBEC3B Preferentially Deaminate the Lagging Strand Template during DNA Replication
…our results indicate that both genetic deficiencies in replication fork-stabilizing proteins and chemical induction of replication stress greatly augment the mutagenesis of APOBEC3A and APOBEC3B. Taken together, these results strongly indicate that ssDNA formed during DNA lagging strand synthesis is a major substrate for APOBECs and may be the principal substrate in human cancers experiencing replication stress.
My comment: Replication is energy-dependent. Nutrient stress and/or social stress lower pH in specific cell types of species-specific tissues, such as blood, and the lower pH promotes viral replication instead of cell type differentiation.
See also: Association of a germline copy number polymorphism of APOBEC3A and APOBEC3B with burden of putative APOBEC-dependent mutations in breast cancer
The results suggest that the APOBEC3A-APOBEC3B germline deletion allele confers cancer susceptibility through increased activity of APOBEC-dependent mutational processes…
My comment: This helps to explain the transgenerational epigenetic inheritance of breast cancer risk factors that should long ago have been linked to virus-driven energy theft.
See also: Virus fighter may have played a key role in human evolution
…our bodies have a group of proteins that have mutated this DNA. These so-called APOBEC proteins seek out certain combinations of the letters that make up DNA (called bases), and, in DNA of viral origin, chemically convert the base cytosine into the base uracil—a change in the genetic alphabet from C to U that can disrupt a gene.
In April 2016, on the Human Ethology Yahoo group, James Gray wrote:
I recently read a book by Svante Paabo who did some of the most important work on ancient DNA. Originally he concluded there had been no interbreeding of modern humans with Neanderthals because he found no evidence of Neanderthal mitochondrial DNA in modern humans. It was only after examining nuclear DNA that he found the 3% to 5% Neanderthal DNA in the human genome. He also found evidence of DNA from another ancient hominid -the Denisovans in the human genome.
My comment: James Gray and the moderator of the group are examples of people who can best be described allegorically as “dumber than dirt” in the context of the fact that even soil bacteria somehow seem to realize that their survival is nutrient-dependent and pheromone-controlled.
See also: A Secret Flexibility Found in Life’s Blueprints: A new study reveals that individual genes can create many different versions of the molecular machinery that powers the cell.
My comment to Quanta [not published] What some people claim is not currently known or unknowable has already linked energy-dependent hydrogen-atom transfer in DNA base pairs in solution from the innate immune system to supercoiled DNA via the physiology of reproduction in all living genera.
For example, Kourtidis et al., (2015)* linked nutrient-dependent microRNA flanking sequences from adhesion molecules to biophysically constrained protein folding. Others have linked virus-driven energy theft to all pathology via the sequencing of the octopus genome.
The most recent integration of what is known about physics, chemistry, and the conserved molecular mechanisms of RNA-mediated protein folding in all living genera was published earlier this month.
See: Polese et al. (2016) Olfactory organ of Octopus vulgaris: morphology, plasticity, turnover and sensory characterization
* Kourtidis et al. (2015) Distinct E-cadherin-based complexes regulate cell behaviour through miRNA processing or Src and p120 catenin activity
See also: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing
In summary, our results support a central role for alternative splicing in network organization, function, and cross-tissue dynamics, demonstrating the importance of an isoform-resolved global view of interactome networks. They also support a paradigm in which most genes encode multiple distinct protein isoforms, each of which potentially yields multiple proteoforms, and where each proteoform possesses a potentially unique set of functions. Collectively, this process would generate a vast diversity of ‘‘functional alloforms,’’ contributing to vastly different physiological and developmental outcomes, disease pathologies, and potentials for therapeutic development.
My comment: The vastly different physiological and developmental outcomes, disease pathologies, and potentials for therapeutic development link energy-dependent changes in base pairs from changes in the microRNA/messenger RNA balance via the immune system to the physiology of reproduction and supercoiled DNA that protects the orgnaized genomes of all living genera from virus driven entropy. In species from microbes to humans, the physiology of reproduction is controlled by the metabolism of nutrients to species-specific pheromones. The overwhelming complexity of the molecular mechanisms that link angstroms to ecosystems was placed into the context of this claim: Feedback loops link odor and pheromone signaling with reproduction
That claim was made 10 years after publication of The Scent of Eros: Mysteries of Odor in Human Sexuality, and 9 years after publication of From Fertilization to Adult Sexual Behavior. (1996)
In 1996, we 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, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994; de Bono, Zarkower, and Hodgkin, 1995; Ge, Zuo, and Manley, 1991; Green, 1991; Parkhurst and Meneely, 1994; Wilkins, 1995; Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.
Many other researchers refused to accept the facts about alternative splicings that we presented in our review. With publication of Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing, 20 years of pseudoscientific nonsense touted by neo-Darwinian theorists has been exposed at the same time the concept of human pheromones is still being placed into representations like this.
Here’s What Happened When I Agreed To Try ‘Smell Dating’
…when a pathogen defeats a host, it has won an evolutionary arms race with the host immune system; cancer, too, proceeds by the generation of phenotypic variation and selection of those cells that are most fit to propagate (see the figure).
My comment: When energy-dependent RNA-mediated DNA repair defeats the pathogen, the organism has adapted via everything known about links from the innate immune system to supercoiled DNA, which protects the organized genomes of all living genera from virus-driven entropy.
Why then, on the eve of my poster presentation at the Genetics and Genomics event, was something like this brought to my attention?
Gene duplication is a common mutational process, occurring with estimated rates of 10−9 to 10−7 new duplicates per gene per generation in flies, worms, and yeast (5, 6). Gene duplication has been of long-standing interest in evolution because, once genes have duplicated, one copy may acquire a novel function (7, 8), and many genes involved in physiological and developmental diversification occur as tandem duplicates in gene complexes.
My comment: The energy-dependent de novo creation of nucleic acids and the energy-dependent de novo creation of G protein coupled receptors allows experience dependent cell type differentiation to lead to ecological adaptation via the innate immune system, the physiology of reproduction, and supercoiled DNA. Energy-dependent creation is not part of a mutational process that links gene duplication to evolution or to the evolution of biodiversity. Creation of energy as information links biophysically-constrained biodiversity via everything known to serious scientists about the links from angstroms to ecosystems in all living genera.