Conserved molecular mechanisms: What is not clear?

Transgenerational Epigenetic Inheritance: Myths and Mechanisms

Heard and Martienssen (2014)

Excerpt 1): “…small RNA signals are highly mobile, being transmitted through the gut in C. elegans, through the vasculature and plasmodesmata in plants, and through exosomes and even serum in mammals. At least in C. elegans, these small RNAs or their derivatives can enter the germline and mediate heritable transcriptional silencing in subsequent generations using histone modification mechanisms analogous to fission yeast.”

Excerpt 2:) “Metabolites might also be transmitted from one generation to the next and participate in bioenergetic feedback loops. These could be propagated over generations and could also act as cofactors for chromatin
modification or RNA processing, for example.”

My comment: In my model, nutrient-dependent pheromone-controlled changes in the microRNA/messenger RNA balance and seemingly futile cycles of thermodynamically controlled protein biosynthesis and degradation result in alternative splicings of pre-mRNA that contribute to organism-level thermoregulation. If the alternative splicings do not stabilize the genome via conserved molecular mechanisms in species from microbes to man, the alternative splicings do not link the epigenetic landscape to the physical landscape of DNA in the organized genome of any species.

Simply put, at best the alternative splicings are beneficial. At worst they result in perturbed protein folding and deleterious mutations.

Between the best and worst of nutrient-dependent pheromone-controlled alternative splicings lies the plasticity of intercellular signaling that may result in de novo creation of proteins that enable increasing organismal complexity in species from microbes to man.

Note however that Heard and Martienssen (2014) was reported as:

End the Hype over Epigenetics & Lamarckian Evolution

Excerpt: “Heard & Martienssen are not convinced. In their Cell review, they admit that epigenetic inheritance has been demonstrated in plants and worms. But, mammals are completely different beasts, so to speak.”

My comment: In our 1996 Hormones and Behavior review article, a section on molecular epigenetics attests to the fact that alternative splicing of pre-mRNA link the conserved molecular mechanisms of [nutrient-dependent] pheromone-controlled physiology of reproduction in species that sexually reproduce.

Excerpt: “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.”

Heard and Martienssen (2014) now report with my emphasis that in Caenorhabditis elegans “…exposure to an olfactory cue early in development affects behavior when encountering the chemical in adulthood, a process known as olfactory imprinting, and this behavior can then be transmitted over more than 40 generations (Remy, 2010). Worms that have been imprinted not only exhibit a more robust ability to migrate toward the chemical but also lay significantly more eggs. Although the mechanisms remain unclear, olfactory imprinting provides a memory of a favorable environment that can be passed onto multiple generations (Remy, 2010). It is possible, therefore, that the very short generation time, acute exposure to the environment, and the abundance of small RNA have predisposed C. elegans, like plants, to dispense with germline reprogramming to some extent and indulge in transgenerational inheritance.

My comment: In Kohl (2013) I reported that “Differences in the behavior of nematodes are determined by nutrient-dependent rewiring of their primitive nervous system (Bumbarger et al., 2013). Species incompatibilities in nematodes are associated with cysteine-to-alanine substitutions (Wilson et al., 2011), which may alter nutrient-dependent pheromone production.”

The mechanisms are perfectly clear. In every species, the nutrient-dependent pheromone-controlled physiology of reproduction links the epigenetic landscape to the physical landscape of DNA.

Claims about the ‘hype over epigenetics’ or claims that the conserved molecular mechanisms of epigenetic effects are not clear, can best be addressed by asking: What is not clear? However, I recognize the fact that it is difficult to clarify anything about biological facts to anyone who has been taught to believe that mutations are somehow involved in species diversity. Thus, no matter how much experimental evidence shows that species diversity results from ecological variation in nutrient availability and the metabolism of nutrients to species-specific pheromones, there will always be theorists who think the conserved molecular mechanisms of cause and effect remain unclear.

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Addendum: If you look at the roles of microRNAs without connecting the networks that lead to cell type differentiation, it will be difficult to understand the diversification of species, which involves cell type differentiation that leads to morphological and behavioral phenotypes.

Interactive networks of glycosylation and microRNAs (miRNAs, piRNAs, siRNAs) in invertebrates and vertebrates

The 25-27nt piRNAs are produced in the gonads.
The ~22 nt miRNAs derive from structured precursor transcripts called primary miRNAs (pri-miRNAs). They are exported to the cytoplasm.
The 21 nt siRNAs originate from processing.