Excerpt: “Mammalian proteins are expressed at ∼103 to 108 molecules per cell (1). Differences between cell types, between normal and disease states, and between individuals are largely defined by changes in the abundance of proteins, which are in turn determined by rates of transcription, messenger RNA (mRNA) degradation, translation, and protein degradation. If the rates for one of these steps differ much more than the rates of the other three, that step would be dominant in defining the variation in protein expression.”
Conclusion: Before gene expression can be correctly modeled, an accurate accounting of molecular abundances and expression rate constants is vital.
Excerpt: “…transcription is in fact the most influential step in determining protein abundance.”
Excerpt: ” transcription makes the largest contribution to protein abundance.
Excerpt: “…much of what was taken to be an effect of translation in the earlier studies is actually a result of experimental errors.”
My comment: The population geneticists who invented neo-Darwinism were wrong. They assumed that de Vries definition of “mutation” could be used to explain the evolution of biodiversity. Instead, olfactory/pheromonal input links the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man.
Epigenetically-effected transcription links RNA-directed DNA methylation and RNA-mediated amino acid substitutions to the exponential increase in proteins that enables the increasing organismal complexity manifested in the morphological and behavioral phenotypes of species from microbes to man.
Nutrient Signaling in Protein Homeostasis: An Increase in Quantity at the Expense of Quality collectively link nutrient-dependent pheromone-controlled fixation of RNA-mediated amino acid substitutions from entropic elasticity to anti-entropic epigenesis and epistasis via biophysically constrained thermodynamic cycles of protein biosynthesis and degradation that link the chemistry of protein folding to RNA-mediated metabolic networks and genetic networks in species from microbes to man.
Insects as models to study the epigenetic basis of disease collectively link the origin of life to the light-induced de novo creation of amino acid substitutions and the exponential increase in the number of proteins. The increase in the number of proteins connects photosynthesis and the physiology of reproduction in plants and animals to the nutrient-dependent pheromone-controlled physiology of reproduction in all animals. For contrast, see:
Summary: Study explains how three essential classes of molecules could have formed simultaneously.
Abstract: Sutherland’s team now reports that it created nucleic acid precursors starting with just hydrogen cyanide (HCN), hydrogen sulfide (H2S), and ultraviolet (UV) light. What is more, Sutherland says, the same conditions also create the starting materials for amino acids and lipids.
My comment to Science:
It’s time to put the pseudoscientific nonsense of ridiculous theories on hold. Serious scientists need to learn more about how the biophysically constrained chemistry of protein folding links viral microRNAs and nutrient-dependent microRNAs from ecological variation and entropic elasticity to anti-entropic epigenesis and epistasis. More than 1000 members of the RNA Society are doing that.
See also: Combating Evolution to Fight Disease
Conclusion: “…the massive creative power of a cooperative RNA consortium (QS-C) remains crucial for life. QS-C was made known to us only recently by virus evolution (e.g., HIV-1). Its role in the origin of life, the emergence of complexity and the creation of group identity should now receive our combined attention” (p. 8).
My comment: The balance of viral microRNAs and nutrient-dependent microRNAs is clearly responsible for the link from RNA-directed DNA methylation and the de novo creation of RNA-mediated amino acids that differentiate all cell type of all species via fixation in the organized genomes of all species in the context of their nutrient-dependent physiology of reproduction. Reports on the origins of life can now be placed into the context of physics, chemistry, and conserved molecular mechanisms that link the epigenetic landscape to the physical landscape of DNA via RNA-mediated events.
Excerpt: “…the C2 sugar glycolaldehyde (1) undergoes phosphate-catalysed condensation with cyanamide (2) to give 2-aminooxazole (3). This heterocycle then participates in a C–C bond-forming reaction with the C3 sugar glyceraldehyde (4), which gives rise to a mixture of pentose aminooxazolines. Reaction of the arabino-configured aminooxazoline (5) with cyanoacetylene (6) then furnishes the anhydronucleoside 7, which on heating with phosphate in urea (8), a by-product of the first step of the sequence, is transformed into ribo-cytidine-2′,3′-cyclic phosphate (9). Ultraviolet irradiation then partially converts this nucleotide into uridine-2′,3′-cyclic phosphate (10) and destroys stereoisomeric impurities.”
Excerpt: “the C2 and C3 sugars 1 and 4 can be provided sequentially by a Kiliani–Fischer-type homologation of hydrogen cyanide (11) using Cu(I)–Cu(II) photoredox chemistry (Fig. 1a, bold green arrows)8,9. Using hydrogen sulfide (12) as the stoichiometric reductant—in which case the inclusion of Cu(I) is no longer essential—we further found that 13–16, the α-aminonitrile Strecker precursors of amino acids glycine, serine, alanine and threonine, are inevitable by-products of this RNA assembly chemistry9, and thereby strengthen its apparent aetiological relevance.”
See for contrast: “…genomic conservation and constraint-breaking mutation is the ultimate source of all biological innovations and the enormous amount of biodiversity in this world” (p. 199).
See also: In July 2014, he [Luis P. Villarreal] co-organized a major conference on viruses in Salzburg, Austria — “DNA Habitats and RNA Inhabitants” [The link opens a pdf of the program] — with philosopher of science Günther Witzany who among other credits to his works is the author of Life is physics and chemistry and communication.
Given the complexity of linking physics, chemistry, and communication from viral microRNAs to nutrient-dependent microRNAs and RNA-mediated amino acid substitutions that differentiate cell types, it is simply amazing that science fiction novelist, Greg Bear predicted in 1999 that “…radical changes in the genome, brought about by mobilization of transposable elements such as human endogenous retroviruses, result in rapid change at the subspecies or species level.”