Psychiatric Illness and microRNA

B0003352 People with DNA fingerprints - artworkUntil quite recently it was thought that only 2% of human DNA making proteins was important. The rest was called “junk.” Junk DNA was thought to accumulate through random processes with no physiological consequences. After the genome project did not find enough “mutations” to explain more illnesses or to explain evolutionary change, 98% of DNA that was left took on new meaning. Ten years after the genome project, ENCODE (research involving over 100 institutions world wide for the encyclopedia of DNA elements) found that a great percentage of the 98% of DNA was significant and operated by forming small and large RNAs that had vital physiological functions. Debate about regulatory DNA now places vital DNA between 20% and 40%. Even at the smaller figure, regulatory DNA is ten times larger than “genes”. It is, also, now clear that 50% of the total DNA consist of jumping genes that have critical importance in evolution (see post on jumping genes).

From Kelvinsong

From Kelvinsong

Thousands of small RNAs have now been found to be vital in all aspects of physiology and genetic regulation. Many large RNAs have dramatic global effects on structure and function of the entire chromatin. Recently it has been found that in psychiatric illness many have altered microRNAs in the brain and in the blood. This post will discuss current findings about psychiatric illness and microRNA. Experiments with animals can show altered behavior with specific microRNAs. These might one day be part of the diagnosis and treatment of brain disease and psychiatric illness.

A previous post described difficulties in characterizing the genetics of psychiatric illness despite strong correlations. Few specific mutations have been correlated exactly with mechanisms of psychiatric illness. Many environmental factors appear to play some role in psychiatric illness including physical and mental stress in early life. Epigenetic mechanisms might also be important, such as tags on DNA and histones, alterations of proteins and RNAs. Small RNAs have been found recently to be a prominent way that alterations in gene expression occur in many areas, notably the brain.

MicroRNA

From Agor153

From Agor153

Each microRNA can alter hundreds of different genes (MicroRNA is usually designated as miRNA – I am using microRNA for ease of reading). Studies show that they are involved in regulation of half of all genes. MicroRNAs have approximately 22 nucleotides. They become part of a complex to silence (alter) existing messenger RNAs about to make proteins. MicroRNA can affect codes in several ways. They can silence a particular strand of messenger RNA. They can disrupt the process. They can block genes. They can slightly alter the results, as often happens in adult neurons. They alter neuronal networks by tuning gene expression in particular ways.

Most research has been with microRNAs in the fetus, during neuroplasticity and in brain disease. But, they also can affect behavior and mood. Current theories of psychiatric illness are looking at altered gene expression that changes brain structures and their activity. Studies include animals and humans, as well as studies of cells. Because of the great complexity involved, multiple approaches are often used at the same time.

Making a MicroRNA

From OgreBot

From OgreBot

Making a microRNA is surprisingly complex. The large RNA polymerase II and III enzymes transcribe microRNAs from DNA. First they make “primary transcripts” from specific genes or from other genes where parts of the DNA (introns) are edited. Either a pri form (primary) as individual microRNAs or clusters are made.

In the first steps of this process, RNA makes a dramatic hairpin curve. Next, editing is done by complex enzymes (ribonucleases) that cut them further, breaking the hairpin turn. Another molecules serves as a ruler to determine the exact places for cuts. Then it is further cut to smaller size of 70 to 110 nucleotides, where it is called a “precursor microRNA”. This is sent out of the nucleus to the cytoplasm where it is cut again by a different enzyme (called DICER) making a double microRNA around 22 nucleotides long.

Then, it is sent to a large complex called RNA induced silencing complex or RISC that helps it silence a gene by placing it in the proper place. One piece of the duplex is complementary to the messenger RNA. The other strand is broken down. RISC takes it to messenger RNA to affect how it is used. Before the final stage it is called mir, but once it is made the microRNA is called miR. An example is miR-35.

Alterations in any of these steps—primary microRNA (pri-miRNA), precursors or pre-miRNAs, mature microRNAs or other factors can change how much microRNA is made. Changes in gene function through tags and different structure can increase or decrease the amounts and the effects. It is a very complex process.

Research In Humans

Human GenomeSee the post on genetics of psychiatric illness for details on the use of specific association studies. Studies on microRNAs have shown changes in chromosomes with codes that are deleted, added and duplicated. These are called copy number variations or CNVs. CNVs are looked for in regions where specific microRNAs have been found in psychiatric illness. Specifically research has looked at sequences in genes that match the microRNA sequences. These are called seeds and seed matches.

One possible important microRNA is called miR-137. Genome wide association study or GWAS of 40,000 people found that miR-137 somehow related to risk for schizophrenia. In this study risk was also associated with a particular version of a gene T rather than G. Normal people had less of miR-137 than schizophrenics. Before these studies associated with psychiatric illness, miR-137 was thought to be related to making new neurons. A large follow up study found the same result. Those with two risk genes in both complementary DNAs were more likely to have schizophrenia and greater changes in brain structure (larger ventricles, less axons and small hippocampus).

RF00246Another study showed miR-137 is associated with fMRI changes in the medial frontal gyrus and is correlated with decreased cognitive abilities. With emotional tasks, other regions were altered such as frontal amygdala and DLPFC (dorso lateral pre frontal cortex). Other studies showed that other genes that are targeted by miR-137 might also be involved in schizophrenia. In fact, four of the places found in the GWAS were targets of this microRNA.

Looking at patient’s brains who have died with psychiatric illness found some particular microRNAs. Although these microRNAs are found after death in a given region, it doesn’t prove it is important in causing problems in life. One study related to major depression found down regulation of miR-1202 in prefrontal cortex. This was found in subsequent studies as well. The finding was worse when there was also anxiety and treatment with antidepressants. This microRNA appears to be somehow related to a glutamate receptor (GRM4).

Another study of miR-135 was related to serotonin in the raphe nucleus in patients who had killed themselves. This microRNA appears to be related to the serotonin transporter (SERT SLC6A4) and receptor 5HT1A.

In Blood

N0020017 Oxygen-carrying red cellMicroRNAs are found in blood and blood cells. They are especially in membrane vesicles, exosomes and bound to proteins. It is not clear how they end up in blood. They may come from cells that died or are secreted actively as signals. They may act as hormones with distant effects (see post on vesicle signals). There is evidence of communication of cells using microRNAs. They may affect nearby brain regions. Previous posts have described microRNAs as part of the vesicle and nanotube signaling between neurons, glia and immune cells.

MicroRNAs in blood have been used as markers for cancer and diabetes. There is more evidence that they are relevant in psychiatric disorders. Study of miR-1202 in depression has the most research. Those patients that responded to antidepressant treatment had different levels of the microRNA. miR-1202 levels are lower at first in those who eventually respond to treatment, but then become greater when the medication works. miR-135a levels were, also, lower with depression and increased when the patients responded to treatment. These were not big studies and need to be repeated. Other studies used miR-16 might also be correlated. The question is whether these microRNAs are involved in the mechanism of depression and its cure.

Another approach is to take blood cells such as lymphocytes from psychiatric patients and study their lineage. But, generation of cell lines may alter the epigenetic mechanism, so this research is just beginning.

In Mice

From Ppgardne

From Ppgardne

In animals, microRNA patterns for each brain region can be described. This can be studied in relation to behavioral changes. Some of these studies involve genetic models where genes are altered in a line of mice. Another type of study uses genetically normal mice who are stressed in different ways and treated with medications. These studies might be relevant in humans.

A new technique captures pairs of RNAs at the same time creating an association. The two types of RNAs in the technique are messenger RNAs creating the protein and the exact microRNA that is affecting it. One study uses mutations involved in Rett syndrome, a devastating brain disease related to autism. Some particular microRNAs were found in the cerebellum related to tags placed on DNA that specifically stimulated these microRNAs. These were related to the vital factor BDNF (brain derived neurotrophic factor), which stimulates new brain cells and improvement in treatment of depression, as well as memory. BDNF has also been associated with Rett syndrome and autism. These converged in a region related to the same miR-132.

Stress produces behavioral effects for generations of mice. The hypothalamic-pituitary-adrenal axis was altered as well as particular microRNAs and messenger RNAs in later generations. Sperm also showed microRNA changes. Another study showed that maternal separation increased anxiety and depression symptoms and altered insulin metabolism. These also showed changes in microRNA as the other study. Injecting this microRNA altered other mice to produce the same behavior and metabolism changes. This shows that microRNAs might be involved in the inheritance of altered behaviors.

Altering microRNA Production

From VTD

From VTD

Early research altered enzymes that produced microRNAs. But, in brain studies this killed neurons. Now, manipulating exact microRNAs has allowed better results. One genetic alteration of the production of a microRNA in gene 8 (DGCR8) has been associated with schizophrenia. Deleting this gene leads to increased risk. In a mouse model, another deletion had a similar effect. Both caused less mature microRNAs in the brain and showed unusual hyperactive behaviors and memory issues.

Another similar study in humans found decrease of miRNA in the pre frontal cortex with schizophrenia after death. A second study study found an increase of different microRNAs in different regions. This particular gene finding in humans related to only 2% of schizophrenic patients. Complex findings of this type were found for miR-185.

In knockout mice, two types of microRNAs were introduced to study miR-16 and its relation to serotonin transporters and effects of antidepressants. More miR-16 was found in noradrenergic cells than serotonin cells. Treatment reduced microRNAs and the serotonin transporter. Complex interactions with these two brain regions were found related to the microRNA.

From Danielewilson01

From Danielewilson01

miR-128b was sent by virus into the infra limbic PFC (pre frontal cortex near the limbic system) in experiments related to fear. With this study, fear in animals could be increased and decreased in different regions by altering microRNAs.

In adult mice, stress altered microRNAs in amygdala with increasing amounts of miR-34. When more miR-34 was introduced using a virus, anxiety decreased even with extreme stress. MicroRNA was noted to have interactions with receptors with the stress related corticotropin releasing hormone. This microRNA was shown to regulate responses to stress.

Another study showed that miR-212 is related to effects of cocaine. With excessive use of cocaine, there was more of microRNA in dorsal striatum. Antagonists reversed this effect. This microRNA increased CREB and other receptors (CREB is a vital factor that affects gene networks named from cAMP response element-binding protein). The effects of these receptors were found to be similar to the effects of the microRNA given.

Other studies found that miR-185 is specifically relevant to neurons and particularly their Golgi related genes. This affects creation of vesicles in the neuron. Also dendrite spines were disrupted when large amounts of the microRNA were given and the opposite effect occurred with too little.

Psychiatric Illness and microRNA

N0024151 Woman suffering from depressionIt is still very difficult to study the biology of psychiatric illness since there are no definite biological markers or mechanisms known for the various illnesses. There are a lot of possible genetic associations that are not precise. A lot more is known about microRNAs in cancer. In brain diseases there is not just one site that is important, but effects can occur in many parts of the brain at once, making study much more complex.

Despite these difficulties, clearly microRNAs are relevant to psychiatric illness and over time more will results will be found.

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  • Thanks for trying to keep others updated, Jon Lieff. I would include suggested reading: http://dx.doi.org/10.1016/j.comppsych.2016.02.009 since this is an open access publication.

    The SNP rs1625579 in miR-137 gene and risk of schizophrenia in Chinese population: A meta-analysis

    “Collectively, our meta-analysis suggested that the SNP rs1625579 in
    miR-137 gene might be involved in schizophrenia susceptibility in
    Chinese Han population. Large scale and multi-center studies in China
    for this association are expected to be performed in near future.”

  • Thanks for trying to keep others updated, Jon Lieff. I would include suggested reading: http://dx.doi.org/10.1016/j.comppsych.2016.02.009 since this is an open access publication.

    The SNP rs1625579 in miR-137 gene and risk of schizophrenia in Chinese population: A meta-analysis

    “Collectively, our meta-analysis suggested that the SNP rs1625579 in
    miR-137 gene might be involved in schizophrenia susceptibility in
    Chinese Han population. Large scale and multi-center studies in China
    for this association are expected to be performed in near future.”

  • Roy Niles
    • And, don’t forget that Roy Niles is the most biologically uninformed antagonist I have ever encountered. See also: https://figshare.com/articles/Nutrient_dependent_pheromone_controlled_ecological_adaptations_from_atoms_to_ecosystems/994281

      “This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the
      microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding;experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man.”

      • Roy Niles

        The laughable thing is, Kohl, that there is no biologist anywhere in the academic and scientific world who has ever come to any of these sites where you post this idiocy and found anything at all there to agree with. That includes Jon Lieff in particular.

    • And, don’t forget that Roy Niles is the most biologically uninformed antagonist I have ever encountered. See also: https://figshare.com/articles/Nutrient_dependent_pheromone_controlled_ecological_adaptations_from_atoms_to_ecosystems/994281

      “This atoms to ecosystems model of ecological adaptations links nutrient-dependent epigenetic effects on base pairs and amino acid substitutions to pheromone-controlled changes in the
      microRNA / messenger RNA balance and chromosomal rearrangements. The nutrient-dependent pheromone-controlled changes are required for the thermodynamic regulation of intracellular signaling, which enables biophysically constrained nutrient-dependent protein folding;experience-dependent receptor-mediated behaviors, and organism-level thermoregulation in ever-changing ecological niches and social niches. Nutrient-dependent pheromone-controlled ecological, social, neurogenic and socio-cognitive niche construction are manifested in increasing organismal complexity in species from microbes to man.”

  • Woohoo. Okay, so you are an oracle (me too, but still somatic) and I don’t want to break your concentration or anything, but if you have time I would like your opinion:
    Such complex biochemistry seems to have a very low probability of success – following this? I find this similar to pursuit of shadow math, like “prime numbers” and really quite simple puzzles that actually are impossible or just stupid, like I think it’s Zeno’s theorem, that continuously halves the distance. Some mathematicians have actually gone off the edge pursuing some of these monkey traps.
    So suppose there is a confounder that doesn’t push but pulls this biochemical train? I’m not there yet – but I’m trying to close a possible gap without forcing it. The other side of the gap is of course functional intelligence – not necessarily conscious at all, but including deep meditation. I know this is your inner-bailiwick as well. Stimulate anything?

  • Scientists ID genes connected to wellbeing, depression and neuroticism
    http://medicalxpress.com/news/2016-04-scientists-id-genes-wellbeing-depression.html

    A pattern “emerged” that consistently links chromosomal rearrangements across all analyses. They report the “emergence” of this pattern outside the context of everything known to serious scientists about how nutrient energy-dependent changes in the microRNA/messenger RNA balance are linked to supercoiled DNA via the innate immune system, which protects all organized genomes from virus-driven entropy.

    Outside the context of the physiology of nutrient energy-dependent reproduction in all genera, they link energy-dependent base pair changes to SNPs and nutrient-dependent triglyceride levels. They report differences in microRNA flanking sequences as if the differences were linked to the quantitative trait loci (eQTL) for seven genes.

    PATTERN RECOGNITION

    Excerpt: “All seven genes are positioned in close proximity to the inversion breakpoints (Fig. 4b), suggesting that the molecular mechanism underlying the inversion’s effect on neuroticism could involve the relocation of regulatory sequences.”

    My comment: They think that everyone is too ignorant to notice that they just linked more that 48000 published works on microRNAs and RNA-mediated cell type differentiation to a report on the identification of genes connected to behavior. They are trying to insert a definition of quantitative trait loci that establishes a boundary between epigenesis and genetics.

    The questions that arise are: What is an eQTL? Where do they come from? How many published works by serious scientists link eQTLs to healthy longevity or from virus-driven energy theft to all pathology? How could a mutated eQTL be linked to behavior as if it was a gene that pseudoscientists linked to the emergence of species-specific behaviors outside the context of the physiology of reproduction, which is nutrient-dependent and controlled by pheromones in species from microbes to humans?

    • Roy Niles

      post hoc, ergo propter hoc
      1. after this, therefore resulting from it: used to indicate that a causal relationship has erroneously been assumed from a merely sequential one.

      • The sequential links are energy-dependent. If my model does not accurately represent the sequence, what is the correct order?

        See for example: Single-residue insertion switches the quaternary structure and exciton states of cryptophyte light-harvesting proteins http://www.pnas.org/content/early/2014/06/11/1402538111.abstract

        • Roy Niles

          Sorry, I don’t want to look at that ridiculous conglomeration again. Why? Because you still can’t see that a link is not the same thing as a cause.

          post hoc, ergo propter hoc
          1. after this, therefore resulting from it: used to indicate that a causal relationship has erroneously been assumed from a merely sequential one.

          • Energy is the cause of all cell type differentiation. Everyone knows that!

            MicroRNA flanking sequences link hydrogen-atom transfer in DNA base pairs in solution to all energy-dependent cell type differentiation. That explains this: Templeton grant funds evolution rethink
            See: http://science.sciencemag.org/content/352/6284/394

            Evolution doesn’t link anything to anything else by what is known about the energy-dependent links from angstroms to ecosystems. All funding will soon be granted to serious scientists.

          • Roy Niles

            Templeton grant funds were supporting the following: “Using a variety of plants, animals, and microbes, the researchers will study the possibility that organisms can influence their own evolution and that inheritance can take place through routes other than the genetic material.” This is very similar to Shapiro’s adaptive mutation theory that I support (and you have vociferously claimed not to).

            As to energy being the cause of all cell type differentiation, every scientist knows that it’s the cause of virtually everything, but scientists are looking for proximate causes, not universal ones – and even then they’re looking for the causative strategies, not just the names of the elements involved.
            You might as well say that Hydrogen and Oxygen cause water, but in fact, without the particular application of energetic forces, they don’t mix, they tend to explode.
            So as I’ve pointed out to others who might take you seriously, you have no concept of what either chemical or physical or biological causation actually entails.
            To quote a scientific source; “To create water, oxygen and hydrogen atoms must be present. Mixing them together doesn’t help; you’re still left with just separate hydrogen and oxygen atoms. The orbits of each atom’s electrons must become linked, and to do that we must have a sudden burst of energy to get these shy things to hook up.”
            As to what evolution links or doesn’t, you have the concept backwards as usual. Biological evolution is the process by which different kinds of living organisms are thought to have developed and diversified from earlier forms during the history of the earth. The best scientists such as Shapiro see it as the adaptive mutation process. You’ve just inadvertently admitted that you don’t see it as a process at all.
            Your energy dependant links are nitwittedly inaccurate “explanations” of the highly complicated means by which systems had become dependant on energy to begin with.
            No serious scientists have ever granted funding to your cockamamie “explanations” and they never will.

          • IntelligentAnimation

            James Shapiro, the first to isolate a gene and the discoverer of retrotransposons, worked with Nobel Prize winning Barbara McClintock, the discoverer of transposons and the motility of genetic information.
            The author of the acclaimed “Evolution: A View from the 21st Century” blasts Neo-Darwinism and replaces it with modern day knowledge of cellular environmental monitoring, gene regulation and cognition. He is known for his highly recommended Natural Genetic Engineering concept in which cells use a toolbox of various mechanisms to edit their own genomes.
            He may very well be one of the two or three most important biologists alive today. I find him to be highly fact-based with extraordinary insight. Has he been granted Templeton fund monies? What is he up to these days?

          • Roy Niles

            Well, unlike Kohl would have it, he hasn’t been stabbed with a knife and claimed to the police or the doctor that the wound was caused by energy.

          • He has still not caught up to the representations Jon Lieff has been making here for several years or to the claims I made in my model, which are based on publication of our 1996 Hormones and Behavior review.

            From Fertilization to Adult Sexual Behaviorhttp://www.hawaii.edu/PCSS/biblio/articles/1961to1999/1996-from-fertilization.html

            Shapiro is like Richard Lenski. They tell “Just So” stories that seem believable to the biologically uninformed because they fail to address the need to link energy-dependent changes from angstroms to ecosystems in all living genera.

          • Roy Niles

            Too bad Jon Lieff has never confirmed any of these claims you’ve made about what you and he are supposed to be in agreement with. But on the other hand, it’s nice to see that you’re confirming what I’ve pointed out about your dissociation with the academic science of biology, and especially your deliberate dissociation with the best of their experimental scientists.

          • Roy Niles

            Too bad Jon Lieff has never confirmed any of these claims you’ve made about what you and he are supposed to be in agreement with. But on the other hand, it’s nice to see that you’re confirming what I’ve pointed out about your dissociation with the academic science of biology, and especially your deliberate dissociation with the best of their experimental scientists.

          • Roy Niles

            Well, unlike Kohl would have it, he hasn’t been stabbed with a knife and claimed to the police or the doctor that the wound was caused by energy.

          • Re: “He is known for his highly recommended Natural Genetic Engineering
            concept in which cells use a toolbox of various mechanisms to edit their
            own genomes.”

            You seem to think that someone who advocates the “magic” of molecular mechanisms that enable cells to edit their own genomes is more important to the future of life on Earth than a magician who performs amazing card tricks.

            Magicians could explain how they perform their tricks. Shapiro doesn’t. He starts with magic and gets from card tricks to pulling rabbits out of a hat, which amazes the biologically uninformed.

          • IntelligentAnimation

            Actually he has never used the word “magic” and he spells out microbiological processes in careful detail. So you are using your own word as code for something else, so you ought to clarify yourself.
            What is it that you have a problem with? What do you disagree with? Using the phoney word “magic” does not clarify anything.
            Shapiro is about as highly regarded and successful as any biologist out there right now.

          • Your ridiculous opinion of him must be based on claims of other biologically uninformed theorists.

          • IntelligentAnimation

            The “biologically uninformed theorists” who strongly recommended his book are Science Medal of Honor winners, including Carl Woese, the discoverer of archaea as a third kingdom of life and Lynn Margulis, who explained endosymbiosis. Of course Shapiro also worked for years side by side with Barbara McClintock herself, the Nobel Prize winner who discovered transposons.
            Shapiro was on the team that first identified a gene (lacZ, I believe) which is no minor feat. Even if you disagree with something he said, there is no denying his importance to what we know about Biology.
            Then again, you didn’t answer what it is about Shapiro that you have a problem with. Attacking people who agree with him (most Biologists) doesn’t explain what you disagree about.
            Again, I ask, what is the problem?

          • IntelligentAnimation

            The “biologically uninformed theorists” who strongly recommended his book are Science Medal of Honor winners, including Carl Woese, the discoverer of archaea as a third kingdom of life and Lynn Margulis, who explained endosymbiosis. Of course Shapiro also worked for years side by side with Barbara McClintock herself, the Nobel Prize winner who discovered transposons.
            Shapiro was on the team that first identified a gene (lacZ, I believe) which is no minor feat. Even if you disagree with something he said, there is no denying his importance to what we know about Biology.
            Then again, you didn’t answer what it is about Shapiro that you have a problem with. Attacking people who agree with him (most Biologists) doesn’t explain what you disagree about.
            Again, I ask, what is the problem?

          • Thanks for asking.

            “Hybrids of Drosophila pseudoobscutra and D. persirnilis are easily obtainable in the laboratory, but they are absent in localities where both species occur side by side (14).” http://www.sciencemag.org/content/177/4050/664.short

            “The entire evolution of the microbial world and the virus world, and the interaction between microbes and viruses and other life forms have been left out of the Modern Synthesis…” — Eugene Koonin http://www.huffingtonpost.com/suzan-mazur/riding-the-evolution-paradigm-shift-with-eugene-koonin_b_7217216.html

            Virus-driven energy theft contributes to all pathology. Energy-dependent changes in base pairs link the biophysically-constrained chemistry of RNA-mediated protein folding from ecological variation to ecological adaptation in all living genera.

            Lynn Margulis explained nutrient-dependent symbiosis in the context of the energy-dependent physiology of reproduction that links ecological variation to ecological adaptation in all living genera. So did I. There is no comparable model for that. That’s is not my problem. It is a problem for pseudoscientists who know nothing about how cell type differentiation occurs.

          • IntelligentAnimation

            Great link, thanks. Koonin Is brilliant.
            I am still at a loss as to how this has anything to do with Shapiro, but he also rejects the modern synthesis, as did Margulis and most all of the most accomplished biologists of our time.
            I would be interested in your comments on how cell type differentiation occurs.

          • Please spend the 7 minutes it takes to learn how cell type differentiation occurs in the context of my presentation during the Molecular Diagnostics conference earlier this month.

            What is life when it is not protected from virus driven entropy https://www.youtube.com/watch?v=K35THJtlhoE

            Koonin and others like him have not linked virus-driven energy theft to all pathology, which means they are not brilliant enough to offer an alternative to the “Modern Synthesis.” It has been several decade since it was invented based on assumptions about how long it would take accumulated mutations to lead to the evolution of a new species — in accord with de Vries 1904 definition of “mutation.”

          • IntelligentAnimation

            Great link, thanks. Koonin Is brilliant.
            I am still at a loss as to how this has anything to do with Shapiro, but he also rejects the modern synthesis, as did Margulis and most all of the most accomplished biologists of our time.
            I would be interested in your comments on how cell type differentiation occurs.

          • Roy Niles

            Lynn Margulis (whose son edited a book sized essay that I was also involved with) was an advocate of adaptive mutation, so for you to claim, now that she’s dead, that your cockamamie theories were in any way supported by her is one of the biggest falsehoods you’ve attempted to slip past us yet.

          • Essential role for a novel population of binucleated mammary epithelial cells in lactation http://dx.doi.org/10.1038/ncomms11400

            They just linked all my claims about the links from the bull sperm microRNAome to microRNAs in breast milk by placing them into the context of “emergence” and “evolution.”

            Ignorance always triumphs until after the inevitable paradigm shift. Roy Niles is proof of that fact.

          • Essential role for a novel population of binucleated mammary epithelial cells in lactation http://dx.doi.org/10.1038/ncomms11400

            They just linked all my claims about the links from the bull sperm microRNAome to microRNAs in breast milk by placing them into the context of “emergence” and “evolution.”

            Ignorance always triumphs until after the inevitable paradigm shift. Roy Niles is proof of that fact.

          • Roy Niles

            No, Kohl, your ignorance has never triumphed, as that cited paper involved experimental work that you have never done, and used the word “emerged” in an entirely different context than it’s being used by you to denote an otherwise unexplainable effect. The word “link” was never used by the authors to denote an unexplained or unexplainable cause, which is the exact opposite from how you use it.
            They didn’t link your claims to anything, as they not only didn’t use emergence as an evolutionary explanation (opposite to the way you might want us to believe), but they used it in their conclusions to state as follows: “that polyploidy is an evolutionarily conserved mechanism to enable successful lactation.”
            You have never concluded anything of a scientific nature from a scientific experiment, or from any experimentation at all for that matter. And you have never found a mechanism that you’ve been able to correctly explain, or even try to, nor have you “linked” any mechanisms together that have been in any way properly explained as causative.
            You’re a fraud and this little demonstration of your usual skullduggery is the proof.

          • RE: “…evolutionarily conserved mechanism to enable successful lactation.”

            The bull sperm microRNAome and microRNAs in breast milk are conserved molecular mechanisms that enable successful lactation in all mammals. One nutrient-dependent base pair change and one amino acid substitution are all that’s required to extend the mouse model of biophyscially constrained protein folding chemistry to humans. That was reported in this study. Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant http://linkinghub.elsevier.com/retrieve/pii/S0092867413000676

            I cited the study in my 2013 review and have no intention of attempting to replicate their findings or anyone’s findings, until someone suggests that another model can be compared to mine.

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

            http://www.ncbi.nlm.nih.gov/pubmed/24693353

          • Roy Niles

            Your 2013 ‘review” stated that “Nutrients are metabolized to pheromones that condition behavior in the same way that food odors condition behavior associated with food preferences.”
            Which is in no way consistent with anything at all in the cited paper, and where your favorite pheromones are never even mentioned
            And it’s a review which is in no way a scientific explanation of anything at all, since pheromones control nothing at all. They are merely inert signals with no biological purposes or strategies of their own.
            Which you continue to fraudulently contend otherwise.

          • Pheromones control the physiology of reproduction in species from microbes to humans.

          • Roy Niles

            Explain how they do that and show us even a single scientific paper (other than one of your “reviews” that backs up that explanation. I’ll love the chance to catch you repeating the same lie again, and acting as if you still don’t know that you’ve been lying.

          • Major histocompatibility complex peptide ligands as olfactory cues in human body odour assessment http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3574394/

          • Roy Niles

            That paper was about peptides that influence reactions to their chemical messages. They don’t control the physiology of reproduction, they carry signals that the receiving bodily systems react to.
            Those are not reproductive reactions, unless you’ve completely misunderstood what biological reproduction entails. Even in the dictionary definition, reproduction means “the action or process of making a copy of something.” There’s no evidence in that paper or elsewhere that peptides control the making of any sort of physiological copying. And they do not control the physiology of any species’ reproductive functions.

          • Feedback loops link odor and pheromone signaling with reproduction
            http://www.ncbi.nlm.nih.gov/pubmed/16290036

          • Roy Niles

            What that says and what I’ve said again and again, and what you can’t seem to understand, is that pheromones carry signals. Signals communicate instructions, but the pheromones that carry them didn’t cause the instructions, nor give them meaning, any more than a telephone that’s used to call you is the cause of the message you receive from it.
            But of course you would prefer to believe that you are reacting to the messenger instead of to the message, and that the blame rests with the messenger for any of the effects that the message itself has only seemed to cause.
            Where biological science is concerned, you’re like the tone deaf looney that can’t play the music and so he blames the tunes.

          • Roy Niles

            The thing you don’t seem to get, Kohl. is that everytime you post one of these dishonest arguments, I simply look for the lies and shoot you down. But you keep lying and worse, the lies don’t get any better. And the evidence that you’re a fraud piles up. And while you apparently think that nobody that you’re interested in defrauding reads these comment sections anyway, you still persist in showing those who do that as well as being fraudulent, you’re somewhat looney.
            And why do I keep on debunking you as a fraud and a loonie? It’s fun.

          • You’re not debunking me. You just claim I am wrong. Anyone can do that. You simply do it with more ignorance than most.

          • Roy Niles

            I’ll agree that anyone can claim you’re wrong, and that some are more ignorant than others. And I’ll agree further that you can’t present a reputable scientist that will claim you’re right.
            Tell us again why you detest Shapiro for example, or deny that you’ve stated earlier that it doesn’t matter that he disagrees with your line of baloney because he and those like him are not reputable

          • Stop putting words in my mouth!

            I do not detest Shapiro. I detest the ignorance of those who do not know how to link energy-dependent changes from hydrogen-atom transfer in DNA base pairs in solution to cell type differentiation in all living genera.

            People like Shapiro appeal to the ignorance of others who know even less than he does. For example, Masatoshi Nei’s textbook was published on the same day as my 2013 review, and people like Perry Marshall use works by Shapiro and Nei to support their ridiculous claims.

            http://www.amazon.com/books/dp/0199661731 “…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).”

            See also: http://shapiro.bsd.uchicago.edu/evolution21.shtml
            “Molecular genetic analysis ultimately revealed that the inducible
            UV repair and mutagenesis capabilities of E. coli and other bacteria
            form part of a complex, highly orchestrated whole-cell response to
            DNA damage labeled the SOS response by Evelyn Witkin, a pioneer of repair and mutagenesis studies [98] [105–107]. The SOS response involves two kinds of repair systems:
            • A precise repair process that removes the UV-damaged DNA
            and does not introduce mutations. This “error-free” process
            operates very much like the mismatch repair proofreading system,
            except that the sensor protein recognizes the characteristic
            chemistry of UV damage in DNA rather than helix
            distortions. It is called excision repair because the result of
            damage sensing, as in mismatch correction, leads to excision of
            a section of the damaged DNA strand [108–110]. (p. 16)”

            Shapiro’s confusion about how UV light repairs DNA damage and Nei’s representations of mutation-driven evolution are cut from the same cloth. The cloth is used to hide that fact that there is no experimental evidence that supports their claims. Experimental evidence of UV light-induced DNA repair is included in my model.
            Among other cited works, I include: Ultraviolet Absorption Induces Hydrogen-Atom Transfer in G⋅C Watson–Crick DNA Base Pairs in Solution http://dx.doi.org/10.1002/anie.201506940

  • Roy Niles

    The next time Kohl refers us to a paper or a site where he shows us what he calls an explanation of what causes what because they can all be linked in sequence, think of this famous fallacy:

    post hoc, ergo propter hoc
    1. after this, therefore resulting from it: used to indicate that a causal relationship has erroneously been assumed from a merely sequential one.

    • More than 49,000 publications indexed on PubMed have established biologically-based cause and effect in the context of energy-dependent links from microRNAs to supercoiled DNA, which protects all organized genomes from virus-driven entropy.

      See for examples: http://www.ncbi.nlm.nih.gov/pubmed/?term=microRNA

      • Roy Niles

        post hoc, ergo propter hoc
        1. after this, therefore resulting from it: used to indicate that a causal relationship has erroneously been assumed from a merely sequential one.