Viruses, amino acids, and somatic cell types (3)

By: James V. Kohl | Published on: August 1, 2015

A co-author of our 1996 Hormones and Behavior review of hormone-organized and hormone-activated behaviors gave her permission to add additional items of interest to this series of blog posts about viruses, amino acids, and somatic cell types. Teresa Binstock is largely responsible for my knowledge of RNA-mediated cell type differentiation. She introduced me and others to the complexity in the section of our review with the title Molecular epigenetics.

It is now understood that certain genes undergo a process called “genomic or parental imprinting.” 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. These sexually dimorphic patterns are labeled genomic or parental imprinting, and these imprintings are inheritable but non-genetic modifications of specific genes…

See also: “RNA mediated DNA methylation” and “RNA mediated
From Teresa:
1) Here’s how I repackaged the exciting news [which links RNA-mediated DNA methylation to cell type differentiation in all genera]:
Expanding the brain: Research identifies more than 40 new imprinted genes
* * * *
open access:
Quantitative and functional interrogation of parent-of-origin allelic expression biases in the brain.

Perez JD, Rubinstein ND, Fernandez DE, Santoro SW, Needleman LA, Ho-Shing O, Choi JJ, Zirlinger M, Chen SK, Liu JS, Dulac C.
Elife. 2015 Jul 3;4. doi: 10.7554/eLife.07860.

The maternal and paternal genomes play different roles in mammalian brains as a result of genomic imprinting, an epigenetic regulation leading to differential expression of the parental alleles of some genes. Here we investigate genomic imprinting in the cerebellum using a newly developed Bayesian statistical model that provides unprecedented transcript-level resolution. We uncover 160 imprinted transcripts, including 41 novel and independently validated imprinted genes. Strikingly, many genes exhibit parentally biased-rather than monoallelic-expression, with different magnitudes according to age, organ, and brain region. Developmental changes in parental bias and overall gene expression are strongly correlated, suggesting combined roles in regulating gene dosage. Finally, brain-specific deletion of the paternal, but not maternal, allele of the paternally-biased Bcl-x, (Bcl2l1) results in loss of specific neuron types, supporting the functional significance of parental biases. These findings reveal the remarkable complexity of genomic imprinting, with important implications for understanding the normal and diseased brain.
* * * *
See also

  • Wang L, Zhang J, Duan J, Gao X, Zhu W, Lu X, Yang L, Zhang J, Li G, Ci W, Li W, Zhou Q, Aluru N, Tang F, He C, Huang X, Liu J. Programming and inheritance of parental DNA methylomes in mammals. Cell. 2014a;157:979–991. doi: 10.1016/j.cell.2014.04.017.
  • [PMC free article]

  • Wang SS, Kloth AD, Badura A. The cerebellum, sensitive periods, and autism. Neuron. 2014b;83:518–532. doi: 10.1016/j.neuron.2014.07.016. 
  • [PMC free article] 

  • Wang X, Sun Q, McGrath SD, Mardis ER, Soloway PD, Clark AG. Transcriptome-wide identification of novel imprinted genes in neonatal mouse brain. PLOS ONE. 2008;3:e3839. doi: 10.1371/journal.pone.0003839. 
  • [PMC free article]

2) Each is open access:
Sex-specific processing of social cues in the medial amygdala.
Bergan JF, Ben-Shaul Y, Dulac C.
Elife. 2014 Jun 3;3:e02743.
Animal-animal recognition within, and across species, is essential for predator avoidance and social interactions. Despite its essential role in orchestrating responses to animal cues, basic principles of information processing by the vomeronasal system are still unknown. The medial amygdala (MeA) occupies a central position in the vomeronasal pathway, upstream of hypothalamic centers dedicated to defensive and social responses. We have characterized sensory responses in the mouse MeA and uncovered emergent properties that shed new light onto the transformation of vomeronasal information into sex- and species-specific responses. In particular, we show that the MeA displays a degree of stimulus selectivity and a striking sexually dimorphic sensory representation that are not observed in the upstream relay of the accessory olfactory bulb (AOB). Furthermore, our results demonstrate that the development of sexually dimorphic circuits in the MeA requires steroid signaling near the time of puberty to organize the functional representation of sensory stimuli.
Neural control of maternal and paternal behaviors.
Dulac C, O’Connell LA, Wu Z.
Science. 2014 Aug 15;345(6198):765-70.
3) You probably know about this. Open access:
Molecular organization of vomeronasal chemoreception.
Isogai Y, Si S, Pont-Lezica L, Tan T, Kapoor V, Murthy VN, Dulac C.
Nature. 2011 Sep 21;478(7368):241-5.
The vomeronasal organ (VNO) has a key role in mediating the social and defensive responses of many terrestrial vertebrates to species- and sex-specific chemosignals. More than 250 putative pheromone receptors have been identified in the mouse VNO, but the nature of the signals detected by individual VNO receptors has not yet been elucidated. To gain insight into the molecular logic of VNO detection leading to mating, aggression or defensive responses, we sought to uncover the response profiles of individual vomeronasal receptors to a wide range of animal cues. Here we describe the repertoire of behaviourally and physiologically relevant stimuli detected by a large number of individual vomeronasal receptors in mice, and define a global map of vomeronasal signal detection. We demonstrate that the two classes (V1R and V2R) of vomeronasal receptors use fundamentally different strategies to encode chemosensory information, and that distinct receptor subfamilies have evolved towards the specific recognition of certain animal groups or chemical structures. The association of large subsets of vomeronasal receptors with cognate, ethologically and physiologically relevant stimuli establishes the molecular foundation of vomeronasal information coding, and opens new avenues for further investigating the neural mechanisms underlying behaviour specificity.
4) More on imprinting. Different folks, different lab.
Parents’ Genes Vie to Influence Offsprings’ Brain, Behavior
July 31, 2015
Genomic imprinting, a mechanism that mutes gene expression in a parent-of-origin manner, can be highly targeted, affecting not just particular tissues, but even tissue subregions, mere clusters of cells—to subtle effect. Subregion-specific imprinting in the brain, for example, has been shown to influence behavior.
This finding emerged from a study conducted at the University of Utah School of Medicine, where researchers focused on a kind of targeted genomic imprinting they call noncanonical imprinting. They used an RNA-sequencing-based approach to detect even modest maternal or paternal allele expression biases at the tissue level….
* * * *
open access:
Paul J. Bonthuis, Wei-Chao Huang, Cornelia N. Stacher Hörndli, Elliott Ferris, Tong Cheng, Christopher Gregg.
Noncanonical Genomic Imprinting Effects in Offspring
Cell Reports, 2015
My comment: Teresa continues to pleasantly provides links to pertinent publications, without comments about the ongoing claims of theorists.
I’ve continued to invite anyone else who is following the current literature on RNA-mediated cell type differentiation to comment here or on my FB pages. Typically, however, my frustration with the theories and the theorists is manifested in the content of my posts.
Pheromones Research
It is obvious to me that evolutionary theorists are not going to acknowledge the paradigm shift, which — largely due to Teresa Binstock’s initial efforts —  is now more than two decades old. Instead, people like Jay R. Feierman, who banned me from participation on the ISHE’s Human Ethology yahoo group, continue to try and sneak in the back door, by posting links to articles that attest to the facts about RNA-mediated cell type differentiation, which he has previously ignored and/or criticized.
Earlier today, for example, he posted links to
Using modern human genetics to study ancient phenomena

Chemosensory discrimination of identity and familiarity in koalas

Experience may allow increasing accuracy of the innate chemosensory recognition of snake predators by Iberian wall lizards

Explaining large-scale patterns of vertebrate diversity

Study of birds’ sense of smell reveals important clues for behavior, adaptation


Now, a large comparative genomic study of the olfactory genes tied to a bird’s sense of smell has revealed important differences that correlate with their ecological niches and specific behaviors.

My comment: What made biologically uniformed human ethologists, like Jay R. Feierman, think that the sense of smell in birds was any less important to RNA-mediated cell type differentiation and ecological niche construction than it is to all other invertebrates and vertebrates? Had other human ethologists and theorists never heard the term “bird flu” or did they simply attribute the virus-driven pathology to mutations in the context of their ridiculous theories about evolution? Is it a wonder that the theorists have not already led to the death of us all. See for comparison: Combating Evolution to Fight Disease. 
See also, my comments at:

It’s time for biophysicists to tell theorists and pathologists how to differentiate between theories about the genesis of different cell types and the biological facts about the nutrient-dependent pheromone-controlled ecological adaptations that enable the genesis of different cell types in individuals of different species. Simply put, it’s time to stop trying to explain ecological adaptations in the context of mutations and evolution.

Summary: Biology to most physicists has much in common with biology to human ethologists and evolutionary theorists. They look at a bird and see a bird. They’ve learned nothing about the bird’s nutrient-dependent pheromone-controlled physiology of reproduction, and cannot link anything known to serious scientists about physics, chemistry, or molecular biology to RNA-mediated events and ecological speciation in birds. Many of them probably still think that birds “evolved” from dinosaurs.
Addendum: After I posted this to my blog, Jay R. Feierman posted a link to this article to the evolutionary psychology yahoo group. Genetics and genomics of autism spectrum disorder: embracing complexity.
In Feierman’s ongoing attempts to obfuscate what is known to serious scientists about medical genetics and biologically-based cause and effect, he presents results from disparate research that most people cannot connect to the validations of our model of RNA-mediated events, which Teresa Binstock helped to integrate earlier today, by adding the reference to:

  • Wang SS, Kloth AD, Badura A. The cerebellum, sensitive periods, and autism. Neuron. 2014b;83:518–532. doi: 10.1016/j.neuron.2014.07.016. 
  • [PMC free article] 

What motivates an MD/Ph.D to attempt to disparage others who might otherwise begin to put their own ideas about biologically-based cause and effect into a complete model linked to autism and other disorders, with origins that must start with gene activation by sensory stimuli, not with mutations?
Could it be Feierman’s oft touted claims about mutations and natural selection?
On 11/1/12: “Random mutations are the substrates upon which directional natural selection acts.
On 2/16/13 : “Random gene mutation is the variance generator upon which natural selection operates.
On 2/23/13: “…random genetic mutations generate the substrate upon which natural selection can act. Random genetic mutations create structural variations in protein enzymes…
Alternatively, could it be the claims made by bird-brained butterfly-watchers who think dinosaurs evolved into birds. See, for example: Birds inherited strong sense of smell from dinosaurs (w/ video)
I think that Dobzhansky would agree with me, if he was not still dead.  The problem seems to be that Feierman, and others like him, never became serious scientists. See BIOLOGY, MOLECULAR AND ORGANISMIC (1964)

The notion has gained some currency that the only worthwhile biology is molecular biology. All else is “bird watching” or “butterfly collecting.” Bird watching and butterfly collecting are occupations manifestly unworthy of serious scientists! I have heard a man whose official title happens to be Professor of Zoology declare to an assembly of his colleagues that “a good man cannot teach zoology. A good man can teach, of course, only molecular biology.
Such pronunciamentos can be dismissed as merely ridiculous. They are, however, caricatures of opinions entertained by some intelligent and reasonable people, whose views deserve an honest and careful consideration and analysis. Science must cope with new problems that arise and devise new approaches to old problems. Some lines of research become less profitable and less exciting and others more so.”

My comment: The attempts of neo-Darwinists, who never learned anything about how viruses are linked to perturbed cell type differentiation, which links them to all pathology, have been wasted on the biologically uninformed. Billions of research dollars also have been wasted on attempts to link beneficial mutations to evolution.
See for comparison: A review of transgenerational epigenetics for RNAi, longevity, germline maintenance and olfactory imprinting in Caenorhabditis elegans
My comment: Catherine Dulac and others have linked olfactory imprinting to imprinted genes in the human brain via the nutrient-dependent pheromone-controlled behavior of nematodes and the development of their primitive nervous systems. How much longer will people like Feierman continue to tout the pseudoscientific nonsense of their ridiculous theories, as if they ever made sense to any intelligent scientist.
No Genetics without Epigenetics? No Biology without Systems Biology?
How does the social environment ‘get into the mind’? Epigenetics at the intersection of social and psychiatric epidemiology
Brain on stress: How the social environment gets under the skin
Mae-Wan Ho: No Boundary Really Between Genetic and Epigenetic
Excerpt 1)

…when we eat food nucleic acids can get into our cells. Also, there is a theory that our cells in the body keep sending out nucleic acids and one theory has it that it seems to correct the mistakes that other cells have suffered from mutations. . . .

1) It is not a theory: it’s a model. Nutrient-dependent/pheromone-controlled adaptive evolution: a model 
Excerpt 2)

evolutionary science has now “moved on to such an extent” that she and Peter Saunders don’t really care anymore about “trying to convince the neo-Darwinists.

2) Neo-Darwinists, like Feierman, prefer their ridiculous theories.
See for comparison: How keeping active pays off in the olfactory system

This ‘use it or lose it’ model explains previously observed changes in olfactory receptor frequency that occur with age (Rodriguez-Gil et al., 2010), or with exposure to odorants (Jones et al., 2008).
Importantly, this model provides an elegant balance between plasticity and adaptation; although the potential to detect a wide range of odours, afforded by the exceptional number of genes for receptors, remains intact, the sensory organ becomes ‘tuned’ and sensitized to odorants relevant to its habitat.

My comment: Food odors and RNA-mediated gene duplication are linked to the experience-dependent de novo creation of olfactory receptor genes. RNA-mediated amino acid substitutions link the de novo creation of olfactory receptor genes and virus-perturbed mutations. If nutrient-dependent organized genomes are not protected from entropy by the availability of food and nutrient-dependent microRNAs viruses link viral microRNAs from entropic elasticity to genomic entropy.
The fact that what organisms eat prevents genomic entropy via the controlled physiology of nutrient-dependent reproduction can be placed into the context of claims that something must prevent mutation-induced damage to organized genomes.
See for instance: He proposed that our scientific understanding of reality is radically incomplete, and that some sort of anti-entropy, order-generating force remains to be discovered.
The discovery that food prevents genomic entropy links Darwin’s ‘conditions of life’ to his theory of how ecological variation leads to ecological adaptations. That fact may be a bigger embarrassment than anyone who has touted the pseudoscientific nonsense about mutations and evolution could ever imagine.
See also: Feedback loops link odor and pheromone signaling with reproduction
Estrogen Permits Vasopressin Signaling in Preoptic Kisspeptin Neurons in the Female Mouse
Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes
Excerpt: The ZAL2 and ZAL2m ER! Alleles Encode Alternative Protein Isoforms.
Alignment of the translated ER! alleles revealed no differences between ZAL2 and ZAL2m in the DNA and ligand-binding domains, which are typically highly conserved across species. For example, ZAL2 and ZAL2m show 77% sequence identity with human ER! across the entire protein and 100% and 94% sequence identity in the DNA and ligand-binding domains, respectively. The ZAL2 and ZAL2m alleles code for 597 amino acids, with two fixed differences driving a Val73Ile and Ala552Thr polymorphism in
My comment: Anyone who claims that the role of fixed amino acid substitutions cannot explain both morphological and behavioral development during life history transitions in all vertebrates and invertebrates, may want to see: Oppositional COMT Val158Met effects on resting state functional connectivity in adolescents and adults, or familiarize themselves with everything else known to serious scientists about how medical genetics is linked from nutritional epigenetics to pharmacogenomics in the context of what is currently known about personalized medicine.

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