Questions about life can be answered in the context of what sustains it.

1) Answers must explain the diversity of life.

2) The diversity of life may help to explain the purpose of life.

3) Explaining the purpose of life may assist anyone who does not think they will live forever.

4) Answers to questions about life that explain life’s diversity must include what is known about the conserved molecular mechanisms that link differences in morphological and behavioral phenotypes in all genera.

Explaining differences in morphological and behavioral phenotypes may help anyone who does not think they will live forever to understand how life is sustained.

Introduction

Answers to questions about what life is can be placed into the context of Molecular and cellular aspects of protein misfolding and disease. Disease is not conducive to to life. See for instance: Medical Genetics: Problems and Approaches.

See for review of ideas about how mutations lead to the evolution of biodiversity Roles of Mutation and Selection in Speciation: From Hugo de Vries to the Modern Genomic Era.

Excerpt: “In the history of evolutionary biology, Hugo de Vries is known as a proponent of the mutation theory of evolution, in which new species are believed to arise by single mutational events (de Vries 1901–1903, 1909, 1910).”

My comment: The authors start with a definition of ‘mutation.’ This leads them to conclude, after a series of assumptions, that “…we have shown that mutation is essential for the evolution of reproductive isolation though selection, particularly deleterious epistatic selection, is necessary.”

For contrast, Erwin Schrödinger’s “What is Life” placed Hugo de Vries definition of mutation into this context:

Excerpt: “The significant fact is the discontinuity. It reminds a physicist of quantum theory -no intermediate energies occurring between two neighbouring energy levels. He would be inclined to call de Vries’s mutation theory, figuratively, the quantum theory of biology.  We shall see later that this is much more than figurative. The mutations are actually due to quantum jumps in the gene molecule.”

My comment: Schrödinger’s ideas about life are consistent with what is currently known. For example:

Life is physics and chemistry and communication

Guenther Witzany clarifies the role of information in the context of quantum jumps in energy levels in genes. Information must be communicated via chemicals that link information transfer to cell type differentiation via the innate ability that all cell types share, which is their ability to recognize cell type differences between self vs non-self. See also: RNA Sociology: Group Behavioral Motifs of RNA Consortia. Information transfer is placed into the context of everything known about RNA-mediated cell type differentiation more than a century later. Baverstock presaged this with his monograph Life as physics and chemistry: A system view of biology. Witzany moves forward via links from physics to chemistry and to the conserved molecular mechanisms of nutrient-dependent protein folding,

Excerpt: “…RNA sociology could explain the de novo generation of nucleic acid sequences and their coherent integration into pre-existing ones, innovation by variations in RNA stem loops and, last but not least, innovative genetic identity by co-evolution.”

De novo creation of nucleic acid sequences and genetic identity

In the context of RNA sociology and RNA-mediated protein folding “…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…” Diamond, Binstock, and Kohl (1996)

That fact links the physics and chemistry of life from the communication of information about epigenetically-effects sex differences in cell type differentiation to all differences in cell types of all individuals of all species. The cell type differences in nucleic acid sequences are RNA-mediated in the context of nutrient-dependent pheromone-controlled feedback loops that link protein folding to morphological phenotypes and to behavioral phenotypes in species from microbes to mammals.

1) Signaling Crosstalk: Integrating Nutrient Availability and Sex microbes

2) Feedback loops link odor and pheromone signaling with reproduction mammals

Moving forward with the current concept of what life is, see:

Human pheromones and food odors: epigenetic influences on the socioaffective nature of evolved behaviors

Epigenetic inheritance uncoupled from sequence-specific recruitment

Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains

Nutrient-dependent/pheromone-controlled adaptive evolution: a model

RNA-mediated epigenetic regulation of gene expression

Whether you start with top-down links from protein folding or with bottom-up links from the epigenetic landscape to the nutrient-dependent physical landscape of DNA in the organized genomes of all species, feedback loops link nutrient-dependent pheromone-controlled reproduction in species from microbes to man. What is known about physics and chemistry links conserved molecular mechanisms from ecological variation to nutrient-dependent ecological adaptations manifested in all species via light-induced and/or food odor-induced RNA-medicated amino acid substitutions that differentiate cell types in plants and animals via changes in protein folding. See, for instance:

A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping reported as DNA Loop-the-Loops with a follow up Inching toward the 3D genome.

Excerpt: “[L]andmark work,” said Francis Collins, the director of the National Institutes of Health (NIH), in a blog post.” The caveat came next: “This 5-year, $24-million-a-year effort, announced in July 2014, will improve the existing techniques and, possibly, come up with new ones. It’s called 4D because the nucleome structure changes as cells age, differentiate, and divide, and researchers want to understand how and why. “…Just as origami paper comes to life only when folded, he says, “nothing in our genome makes sense except in 3D.”

My comment: Do we really need a 5-year, $24-million-a-year effort that can, at best, echo Dobzhansky’s claim that Nothing in Biology Makes Any Sense Except in the Light of Evolution. I think NIH researchers need to stop ignoring the fact that in the same article Dobzhansky claimed: “…the so-called alpha chains of hemoglobin have identical sequences of amino acids in man and the chimpanzee, but they differ in a single amino acid (out of 141) in the gorilla.”

My comment to Science (submitted Jan 2, 2015; published on Jan 8, 2015):

Re: “…the nucleome structure changes as cells age, differentiate, and divide, and researchers want to understand how and why.”

Cell type differentiation is nutrient-dependent. RNA-directed DNA methylation links RNA-mediated amino acid substitutions to cell type differentiation via protein folding during life history transitions. Amino acid substitutions stabilize protein folding; mutations perturb it, during nutrient-dependent theromodynamic cycles of protein biosynthesis and degradation.

Life is physics and chemistry and communication — http://dx.doi.org/10.1111/nyas.12570

The metabolism of nutrients links metabolic networks to genetic networks via species-specific pheromones that control the physiology of reproduction. Simply put, pheromones link nutrient-dependent life via physics, chemistry, and the conserved molecular mechanisms of communication in species from microbes to man.

Until nutrient-dependent protein folding is linked via the conserved molecular mechanisms of amino acid substitutions and pheromone-controlled DNA stability in organized genomes, which links the epigenetic landscape to the physical landscape of DNA, researchers must take a piece-meal approach to integrating the requirements for life and successful life history transitions — despite the fact that life history transitions have been detailed in the context of the honeybee model organism. See: Honey bees as a model for understanding mechanisms of life history transitions http://www.ncbi.nlm.nih.gov/pubmed/15925525

See also my comments to The Scientist re: A new full-genome map indicates how DNA is folded within the nuclei of human cells.

12/12/14

Nutrient-dependent/pheromone-controlled adaptive evolution: a model. Excerpt: “A form of GnRH associated with sexual orientation in yeasts links control of the feedback loops and developmental processes required for nutrient acquisition, movement, reproduction, and the diversification of species from microbes to man [via RNA-directed DNA methylation and RNA-mediated amino acid substitutions that stabilize protein folding in the DNA of organized genomes].

I think this report on how DNA is folded within the nuclei of human cells makes it obvious that nutrient-dependent pheromone-controlled RNA-mediated amino acid substitutions, protein folding, and feedback loops link the epigenetic landscape to the physical landscape of DNA via what is currently known about the bio-physically constrained chemistry of protein folding and the conserved molecular mechanisms of cell type differentiation.

For cross species examples that include the honeybee model organism, see my 2012 and 2013 reviews, which are based on what we (T.B.) included in the molecular epigenetics section of our 1996 Hormones and Behavior review: From Fertilization to Adult Sexual Behavior  and on extension of RNA-mediated cell type differentiation to insects in Organizational and activational effects of hormones on insect behavior and to the life history transitions of honeybees in Honey bees as a model for understanding mechanisms of life history transitions.

12/15/14

I think the lack of response here can be attributed to what is now known about protein folding and cell type differentiation. It can be compared to the claims of theorists that “…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) Nei (2013)

Two additional video representations of what is currently known about physical and chemical constraints on the conserved molecular mechanisms of nutrient-dependent protein folding can now be compared.

One links thermodynamic cycles of protein biosynthesis and degradation to cell type differentiation via amino acid substitutions in species from microbes to man. ISHE Summer Institute 2013

One links mutations to cell type differentiation in a mouse to human model. 2 Cell Studies Reveal Genetic Variation Driving Human Evolution

Taken together with the video that reveals the priciples of chromatin looping,  less than 25 minutes of video representations could be used as a basis for conclusions about cell type differentiation that would move science forward — minimally, into the current century.  Is that a problem?

12/17/14

I realize that most of the biologically uniformed are already concerned that they were taught to believe in a ridiculous theory based on the pseudoscientific nonsense of definitions and assumptions. However, I cannot help but add another level of examination that evolutionary theorists seem to have ignored as they touted their ridiculous theories.

What about The ribosome as a missing link in the evolution of life

In theory, it links nutrient-dependent RNA-mediated events to cell type differentiation across all genera, and that takes us back to this claim:

“We cannot conceive of a global external factor that could cause, during this time, parallel evolution of amino acid compositions of proteins in 15 diverse taxa that represent all three domains of life and span a wide range of lifestyles and environments. Thus, currently, the most plausible hypothesis is that we are observing a universal, intrinsic trend that emerged before the last universal common ancestor of all extant organisms.” — A universal trend of amino acid gain and loss in protein evolution

The problems with use of de Vries definition of ‘mutation’ and assumptions about how cell type differentiation occurs in species from microbes to man is the lack of pattern recognition AND the the lack of experimental evidence of biologically-based cause and effect that links the epigenetic landscape to the physical landscape of DNA in organized genomes of species from microbes to man. That problem has led to claims about constraint-breaking mutation that defy any common sense approach to cell type differentiation in any organism that eats or reproduces.

Coelacanths and birds eat and reproduce. GnRH and GnRH receptors link their nutrient-dependent physiology of pheromone-controlled reproduction to the honeybee model organism via its hormone-organized and hormone-activated behaviors. Pattern recognition suggests that dinosaurs did not evolve into birds because nutrient-dependent pheromone-controlled amino acid substitutions link coelacanths to mammals via conserved molecular mechanisms of cell type differentiation.

Is anyone who plans to continue touting theories about mutations and evolution willing to address the concerns that others may have about the end of that pseudoscientific nonsense as others begin to examine the biological basis of cause and effect?

Moving forward

Two weeks after the article about chromatin looping was published, the epigenetic landscape was linked to the physical landscape of DNA in organized genomes via RNA-mediated events that link single amino acid substitutions to cell type differences in all all cells of all individuals of all species. See: Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains reported on January 1, 2015 as:

Defying textbook science, study finds new role for proteins.

Excerpt: “New RNA sequencing techniques showed that the Rqc2/ribosome complex had the potential to add amino acids to stalled proteins because it also bound tRNAs, structures that bring amino acids to the protein assembly line.”

My comment: Textbook ‘science’ was defied by the link from RNA-mediated protein folding to DNA repair via amino acid substitutions in the context of cell type differentiation. We reported what was known about RNA-mediated cell type differentiation in our 1996 Hormones and Behavior review: From Fertilization to Adult Sexual Behavior. Nothing about cell type differentiation has changed.

Excerpt 1) “Early in embryonic development attached methyl groups become removed from most genes. Several days later, methyl groups are reattached in appropriate sites. Fascinatingly, some such genes reestablish methylation patterns based upon whether the chromosomal segment carrying the gene came from maternal or paternal chromosomes.”

Excerpt 2) “Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins…”

Excerpt 3) “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…”

In the century that has passed since de Vries defined ‘mutation,’ serious scientist have learned that RNA binding proteins link protein folding from nutrient-dependent RNA-directed DNA methylation and the physiology of nutrient-dependent reproduction to RNA-mediated fixation of amino acid substitutions and to the protein folding that enables developmental differences in “…nucleome structure changes as cells age, differentiate, and divide.

The honeybee model organism exemplifies what we detailed in our 1996 review. See: Honey bees as a model for understanding mechanisms of life history transitions (2005) and Organizational and activational effects of hormones on insect behavior (2000).

Excerpt from 2000 with my emphasis: “The development of species-typical and sex-specific adult behaviors in vertebrate animals is influenced by gonadal steroid hormones, non-gonadal hormones, and non-hormonal factors working on the underlying neural circuitry (reviewed in Diamond et al., 1996; Kawata, 1995; Schlinger, 1998). Effects of hormones on brain and behavior occur through three mechanisms: (1) behaviors both organized and activated by hormones, (2) behaviors only organized by hormones, and (3) behaviors only activated by hormones (reviewed in Arnold and Breedlove, 1985; Diamond et al., 1996).”

I emphasize Diamond et al., 1996 because Milton Diamond subsequently defied John Money’s textbook science. Our review presaged what few others besides Milton Diamond could have seen coming. See: Sex reassignment at birth: Long-term review and clinical implications. Diamond and Sigmundson (1997) ended the long-running nature/nurture debate and placed sexual differentiation of cell types into the context of molecular epigenetics and RNA-mediated events that we now know link RNA-mediated amino acid substitutions to the differentiation of all cell types in all individuals of all species.

Who else knew about RNA-mediated cell type differentiation? Among those who suspected the link from RNA-mediated sex differences in cell types to sexual orientation should have been those who read the book: As Nature Made Him: The Boy Who Was Raised as a Girl. It has never since been argued that the nature of our genetic networks is not linked via experiences during life histories to behavioral phenotypes that include differences in sexual orientation. Therefore, I reiterate: 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).”

Since 1996, genetic and evolutionary research programs have stagnated. For example, see: Explaining Same-Sex Sexual Behavior: The Stagnation of the Genetic and Evolutionary Research Programs.

Excerpt: “…whereas this model may be normatively appropriate for sciences that are axiomatically structured such as physics, this case study has shown that the Lakatosian methodology may not be normatively appropriate for sciences that deal with human behavior.”

My comment: The stagnation of genetic and evolutionary research programs has occurred during the time when everything learned about cell type differentiation since 1996 includes links from physics and the chemistry of protein folding to conserved molecular mechanisms of RNA-mediated cell type differentiation. The question that arises is “What went wrong?” How could anyone interested in cell type differentiation not learn about how it occurs during the 18 years since we detailed cell type differentiation in the context of RNA-mediated epigenetic regulation of gene expression?

Until now, what have you learned about protein folding in the context of Medical Genetics: Problems and ApproachesBiological imprinting: Some genetic considerations; or Biological evolution: Some genetic considerations? If you haven’t learned anything about nutrient-dependent RNA-mediated epigenetic regulation of protein folding, you could not have learned anything about gene expression, about life, or about the origin of life. Most likely, if you have learned anything at all about life, everything you have learned has been placed into the context of The Origin of Life Circus.

You’ve watched that circus ‘come through town’ and you’ve watched experts on human sexuality and other experts frustrated attempts to place animal behavior into the context of the epigenetically-effected physiology of reproduction and behavior. They can’t do that with their ridiculous theories about mutations and evolution. See for example: Replace the Modern Synthesis (Neo-Darwinism): An Interview With Denis Noble.

Excerpt: “[W]hat Haldane, Fisher, Sewell Wright, Hardy, Weinberg et al. did was invent…. Evolution was defined as “changes in gene frequencies in natural populations.” The accumulation of genetic mutations was touted to be enough to change one species to another….  Assumptions, made but not verified, were taught as fact.”

My comments: The experts on human sexuality continued to make assumptions that appear to be based on de Vries definition of ‘mutation.’ This suggests that all theorists can do is keep touting pseudoscientific nonsense about biologically-based cause and effect in the context of sex differences in cell types and sexual orientation, while they ignore other nutrient-dependent pheromone-controlled cell type differentiation. What will they do when the evolution industry finally collapses under the weight of its decades-old misrepresentations about what DNA (genes) can do? Serious scientists already have placed cell type differentiation into the context of RNA-mediated events and the physiology of reproduction, but pseudoscientists seem willing to hang onto the threads of their theories as all of them are torn apart and replaced by what in known about protein folding.

Therein lies the problem I had hoped to succinctly address when I started this blog post. It was going to be about Guenther Witzany’s answer to Erwin Schrödinger’s question “What is Life” Obviously, the answer is simple: Life is physics and chemistry and communication, but some people want life to be about mutations and the evolution of biodiversity. Anyone who tries to tell biologically uninformed theorists that life cannot be about mutations and the evolution of biodiversity is, whenever possible, silenced. But no one can keep others from eventually learning enough about physics, chemistry, and conserved molecular mechanisms. That fact has become clear.

The Genetics of Society

Excerpt: “New, affordable sequencing technologies enable scientists to examine how genes across the entire genome are regulated to generate different caste phenotypes, the roles of DNA methylation and microRNAs in this differential expression, and what proteins are synthesized as a result. This burgeoning area of research, dubbed “sociogenomics” in 2005 by Gene E. Robinson,1 is revolutionizing our understanding…”

My comment: Sociogenomics has lagged behind research results portrayed in the context of evolved biodiversity at a time when it has been clear, at least since 1996, that behaviors do not evolve. Behavior is exhibited in the context of food odors and pheromones which makes it clear that species do not evolve into other species. Their nutrient-dependent pheromone-controlled physiology of reproduction either enables them to adapt to ecological variation or they become extinct. Again, see: RNA Sociology: Group Behavioral Motifs of RNA Consortia RNA-mediated events enable ecological adaptations manifested in morphological and behavioral phenotypes. The fossil record exemplifies extinction, not natural selection in the context of mutations and the evolution of biodiversity.

See also my comments to The Scientist about this article:

Genomes Gone Wild

Excerpt: “Plants are a model system for comparative genomics and other processes,” says Palmer. In polyploidy, transposable elements, and rates of mutation, plants lead the way.

My comment: If plants led the way with their rates of mutation, it would be less likely that biological energy could be linked from light-induced amino acid substitutions that differentiation cell types in plants and in animals to nutrient-dependent pheromone-controlled cell type differentiation in all animals. See for example: Single-residue insertion switches the quaternary structure and exciton states of cryptophyte light-harvesting proteins.

Excerpt: “The switch between forms is ascribed to the insertion of a single amino acid in the open-form proteins.”

My comment: In the context of physics, these authors claim “The emergence of two forms appears to have been caused by a single insertional/deletional mutation in the new cryptophyte α subunit.” Simply put they decided to claim the amino acid substitution was a mutation, which is what evolutionary theorists like to claim. The link the biological energy of the sun to plant and animal life via the definition of ‘mutation’ by accepting use of that term as if it made sense in the context of physics and the chemistry of protein folding. Serious scientists and theorists appear to have reached an impasse.

“Over time, mutations supply the raw material from which new life forms evolve” and “Substitution is a type of mutation where one base pair is replaced by a different base pair. The term also refers to the replacement of one amino acid in a protein with a different amino acid” are not interchangeable concepts of biologically-based cause and effect.

How could the link from bio-physically constrained protein folding in RNA lead to mutations in DNA and evolution of biodiversity? The question arises in the context of a book written by the current director of the National Institute of Health. Francis Collins, wrote: The Language of God: A Scientist Presents Evidence for Belief. In his book, DNA is the language. Does anyone believe that any language could evolve via mutations in the letters of the language during its development. If so, they could make their case for what is called theistic evolution and also make a case for mutations causing dinosaurs to evolve into birds during the millions of years it supposedly took them to do it.

Here is where the evolutionary theorist’s story-telling run head-first into facts about bio-physically constrained RNA-mediated protein folding and cell type differentiation.

Rates of Dinosaur Body Mass Evolution Indicate 170 Million Years of Sustained Ecological Innovation on the Avian Stem Lineage

Excerpt: “Animals display huge morphological and ecological diversity. One possible explanation of how this diversity evolved is the “niche filling” model of adaptive radiation—under which evolutionary rates are highest early in the evolution of a group, as lineages diversify to fill disparate ecological niches.”

My comment: There is no mention of mutations in the context of ecological innovation across 170 million years.

See also: Gradual Assembly of Avian Body Plan Culminated in Rapid Rates of Evolution across the Dinosaur-Bird Transition reported as: Dinosaur family tree gives fresh insight into rapid rise of birds.

Excerpt: “Based on their findings from fossil records, researchers say the emergence of birds some 150 million years ago was a gradual process, as some dinosaurs became more bird-like over time. This makes it very difficult to draw a dividing line on the family tree between dinosaurs and birds.”

My comment: Findings from the fossil record tell us nothing about the nutrient-dependent pheromone-controlled physiology of reproduction that must also link the evolution of species-specific behaviors to morphological and behavioral phenotypes in species from microbes to man via conserved molecular mechanisms of bio-physically constrained chemistry linked to RNA-mediated protein folding.

See also: Comparative genomics reveals insights into avian genome evolution and adaptation reported as: ‘Big Bang’ of bird evolution mapped: Genes reveal deep histories of bird origins, feathers, flight and song

Journal article Excerpt:  Detection of positively selected amino acids at 137 Q (dN/dS = 2.153) and 378 R (dN/dS = 2.153) in all birds provided additional support for diet-related adaptation in AGT (positions according to human AGT; posterior probability > 99%; P < 0.0001).

News article Excerpt: “…a comparison between the genomes of living bird species and those of vertebrate species that have teeth identified key mutations in the parts of the genome that code for enamel and dentin, the building blocks of teeth. The evidence suggests that five tooth-related genes were disabled within a short time period in the common ancestor of modern birds more than 100 million years ago.”

My comment:  I reiterate: The most recent statement about evolution from the NIH states: Over time, mutations supply the raw material from which new life forms evolve (see Chapter 3, “Life’s Genetic Tree”). [This page last reviewed on June 9, 2011]

That statement can be compared to what is currently known about ecological variation and natural selection. See: Tracking niche variation over millennial timescales in sympatric killer whale lineages.

Excerpt 1) “Ecological variation is the raw material by which natural selection can drive evolutionary divergence [1–4].”

Excerpt 2) “…differences in amino acid composition among different tissues can lead to large differences in trophic discrimination [38].

My comment: The simplest amino acid is achiral glycine where the R group is just a hydrogen atom. Substitution of the only achiral amino acid in the structure of the decapeptide gonadotropin releasing hormone (GnRH) appears to have stabilized nutrient-dependent RNA-mediated cell type differentiation that evolutionary theorists claim occurred during ~600 million years of evolution. “During at least 600 million years of evolution the N and C termini of GnRH have been conserved as functional domains for binding and activating cognate receptors to accomplish these functions.”

See also: Evolution of gonadotropin-releasing hormone (GnRH) structure and its receptor

Excerpt: “It is possible that GnRH has an early origin in life history as a regulator of reproduction, since yeast α mating factor has 80% amino acid homology with mammalian GnRH and stimulates gonadotropin release from the mammalian pituitary (Loumaye et al., 1982; King and Millar, 1995). There is a question whether the structure of the GnRHs and their receptors in invertebrates conserved their structure during evolution in a sufficient degree to support the homology with the structure of GnRHs and their receptors in vertebrates.”

In the context of a microbes to man model of nutrient-dependent pheromone-controlled ecological adaptations, we could start with yeasts in A Deubiquitinating Enzyme Interacts with SIR4 and Regulates Silencing in S. cerevisiae. However, it appears that mutations in ubiquitin processing enzymes silence gene expression in yeast and Drosophila, which suggests the regulation of silencing by these enzymes is an evolutionarily conserved process. The question arises: “What is an evolutionarily conserved process?”

In the same year, our answer to that question was that RNA-directed DNA methylation was the nutrient-dependent pheromone-controlled process that linked microbes to mammals via cell type differentiation. In From Fertilization to Adult Sexual Behavior we (TB) wrote:

“Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993; Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991; Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). 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.”

See also:

1) Signaling Crosstalk: Integrating Nutrient Availability and Sex microbes

2) Feedback loops link odor and pheromone signaling with reproduction mammals

Excerpt: “Indications that GnRH peptide plays an important role in the control of sexual behaviors suggest that pheromone effects on these behaviors might also involve GnRH neurons.” (p 683).

My comment: Hagfish and coelacanths are referred to as living fossils. Both appear to refute evolutionary theories that try to link mutations across millions of year.

Hagfish: “…because central control of reproduction is perhaps the most basic function of the vertebrate H-P axis, and given the importance of GnRH in this network, research on GnRH in hagfish can help elucidate the early evolution of the H-P system itself.”

Coelacanths: “Skate and coelacanth are the only examples of animals with both type I and II GnRH receptors and all three peptide types, suggesting this was the ancestral condition in vertebrates.”

See also: Dynamic evolution of the GnRH receptor gene family in vertebrates

Excerpt 1) “Our analysis revealed the presence of five subfamilies of GnRH receptors in vertebrates; remarkably, coelacanths possess intact genes for all five subfamilies.”

Excerpt 2) “Our results provide a novel evolutionary framework for generating hypotheses concerning the functional importance of structural characteristics of vertebrate GnRH receptors. We show that five subfamilies of vertebrate GnRH receptors evolved early in the vertebrate phylogeny, followed by several independent instances of gene loss. Chief among cases of gene loss are humans, best described as degenerate with respect to GnRH receptors because we retain only a single, ancient gene.

Excerpt 3) “…humans should be viewed as among the most degenerate species with respect the GnRH receptor evolution because we retained only one member of five potential subfamilies, and the retained gene is from one of the most ancient subfamilies.”

Taken together, the information on GnRH and GnRH receptors links the substitution of the only achiral amino acid: glycine to nutrient-dependent pheromone-controlled ecological adaptations in species from yeasts to mammals.

Regulation of gonadotropin-releasing hormone neurons by glucose

Excerpt: In summary, the work described here suggests that direct glucosensing might contribute to the response of the reproductive system to fluctuations in nutrient availability. Combined with previous work implicating distal brain regions in the metabolic control of GnRH neurons, these findings suggest a model (Figure 2) in which direct glucosensing functions together with afferent signals to ensure that reproduction occurs only in the presence of an adequate nutrient supply.

The complexity of glucosensing; thermodynamic cycles of protein biosynthesis and degradation; and cell type differentiation via nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions now extends to unsuspected interactions among different receptors that link vitamin D to glucocorticoid receptors and androgen receptors and to transgenerational epigenetic inheritance via maternal and paternal imprinting. See for example: Identification of nuclear hormone receptor pathways causing insulin resistance by transcriptional and epigenomic analysis reported as: Epigenomics analysis reveals surprising new clues to insulin resistance.

Excerpt 1) “Fetal programming centers on a person’s exposure in utero,” he explains. “So, for example, whether a fetus has received too few or too many nutrients from the mother can lead to a person becoming obese or diabetic in adulthood, and this in turn can be passed along to the next generation. There is a lot of evidence that insulin resistance can be passed on this way and this type of intergenerational event almost certainly develops in the nucleus.”

Excerpt 2) “Our findings were unanticipated for several reasons,” says Rosen. “First, TNF is a strong inducer of inflammation, while the GR protects against inflammation. Showing that TNF exerts at least some of its actions via the GR is somewhat heretical. Additionally, higher vitamin D levels have been correlated with better insulin sensitivity, so it was surprising to see the VDR associated with insulin resistance. These results call into question some of the basic assumptions surrounding the relationship between vitamin D and metabolic health. Most importantly, these data tell us that we have an awful lot still to learn about the basic mechanisms by which diabetes is triggered, and they reveal new ways in which we can approach drug therapy for this disorder.”

In the context of 1) Life as physics and chemistry: A system view of biology or 2) Life is physics and chemistry and communication, reduced sun exposure in the physically inactive has been tentatively linked to differences in insulin sensitivity via intranuclear interactions among tumor necrosis factor (TNF); glucocorticoid receptor (GR); androgen receptor (AR); vitamin D; vitamin D receptor (VDR) and sequestration of fat-soluble vitamin D in the adipose tissue of obese subjects.

1) “…when deprived of nutrient the cell expresses all the genes it has and if a combination of those genes will allow growth they are selected as an adaptive attractor. This is in effect self-organisation of the gene products at the genome level.”

2)  “…the genetic code is not just used metaphorically: it represents a real natural language… a natural language or code emerges from populations of living agents that communicate.

Chemical communication links olfactory/pheromonal input from the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from micobes to man via thermodynamic cycles of nutrient-dependent protein biosynthesis and degradation. Mutations perturb RNA-mediated protein folding and lead to loss of function or to pathology. There is no such thing as a beneficial mutation because perturbed protein folding cannot lead to increasing organismal complexity. Mutations cannot be linked to the evolution of biodiversity except in the context of olfactory receptor gene loss that occurs with increasing genomic stability via the de novo creation of olfactory receptor genes linked from nutrient uptake to the pheromone-controlled physiology of reproduction in species from microbes to man.

Simply put, there is no such thing as a beneficial mutation, but mutations are not due to your bad luck.

BAD LUCK

Stem Cell Divisions Help Explain Cancer Risk

Certain organs and tissues may be more prone to cancer than others for a variety of reasons besides the actual number of stem cells that they possess.

I wrote:

If you exclude everything currently known to serious scientists about protein folding…

These authors eliminated everything known about protein folding, which is linked from nutrient uptake and obesity to estradiol receptor content in tissues most prone to sex differences in cancer rates.

S.Pelech-Kinexus reitterates that fact with extended comments that provide no alternative except to accept Nei’s claims about constraint-breaking mutations in the context of his book Mutation-Driven Evolution. However, S.Pelech-Kinexus also notes:

The health of the immune system is highly dependent on environmental factors such as the availability of nutrients…

In a New Approach to Fighting Disease, Helpful Genetic Mutations Are Sought

Is there something not clear about the fact that nutrient-dependent RNA-directed DNA methylation and RNA-mediated amino acid substitutions differentiate all cell types in all individuals of all genera?  If so, tell me what is not clear so that I can explain it better than I did with the model and with examples across species in Nutrient-dependent/pheromone-controlled adaptive evolution: a model.

My review was published on the same day as Nei’s book: Mutation-Driven Evolution, but no one has compared his conclusion about constraint-breaking mutations to my conclusion.

…the model represented here is consistent with what is known about the epigenetic effects of ecologically important nutrients and pheromones on the adaptively evolved behavior of species from microbes to man. Minimally, this model can be compared to any other factual representations of epigenesis and epistasis for determination of the best scientific ‘fit’.

Instead, we see yet another example of pseudoscientific nonsense about mutations in the context of some cancers, which are not beneficial, while excluding sex differences in cancers, which are not beneficial. The question arises, again: Where can the constraint-breaking mutations be found that contribute to mutation-driven evolution and why aren’t mutations differentiated from amino acid substitutions that link the epigenetic landscape to the physical landscape of DNA in the organized genome of species from microbes to man via the bio-physically contrained chemistry of protein folding in all cell type of all individuals of all species?

Top-down causation: an integrating theme within and across the sciences?

Excerpt: “Areas where striking progress is being made in this regard are epigenetics [22] and social neuroscience [23]. These papers are in fact dealing with top-down causation: the way they provide experimental confirmation of this concept needs to be made more explicit.”

See also:

Origin of the Eukaryotic cell: Part II – Cytoskeleton, membranes, and beyond Dec 17, 2014

The biological spoils of war: Study finds those who take part in violent conflict have more wives, children Dec 29, 2014

Scientists identify patterns of RNA regulation in the nuclei of plants Dec 31, 2014

‘Bad luck’ of random mutations plays predominant role in cancer, study shows Jan 1, 2015

Keep Reading