Becoming biologically informed

By: James V. Kohl | Published on: July 6, 2015

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RNA-mediated pathogenic mechanisms in polyglutamine diseases and amyotrophic lateral sclerosis

Abstract excerpt:

In this article, we describe various common RNA toxicity pathways, namely epigenetic gene silencing, nucleolar stress, nucleocytoplasmic transport, bi-directional gene transcription, repeat-associated non-ATG translation, RNA foci formation and cellular protein sequestration.

Journal article conclusion:

Although protein toxicity was considered to play a major role in the pathogenesis of repeat expansion diseases, we now know that mutant transcripts also induce cell dysfunction and death via multiple mechanisms, such as the alteration of gene expression levels and splicing patterns, the generation of small RNAs, the induction of nucleolar stress, the promotion of bi-directional transcription and repeat-associated non-ATG translation of the disease locus, the activation of apoptotic signaling, and the sequestration of cellular components to RNA foci. The above RNA-mediated mechanisms are predicted to operate in conjunction with the protein-mediated pathways to confer overall neurotoxicity. We now know that mutant RNAs confer cytotoxicity by sequestering cellular components to RNA foci (Wojciechowska and Krzyzosiak, 2011). The identification of the individual polyQ protein species, including the monomer, oligomer, protofibril, fibril and inclusion body, has greatly facilitated the study of polyQ protein toxicity (Hands and Wyttenbach, 2010). Technologies and strategies that result in a detailed classification of individual mutant RNA species will allow more in-depth and systematic investigations of the RNA-mediated pathogenesis of neurodegeneration.

My comment: All mutations perturb protein folding.
See also: This video is about RNA-mediated amino acid substitutions and protein folding.

My comment: The difference between mutations, which perturb protein folding, and RNA-mediated amino acid substitutions, which stabilize the organized genomes of all genera via the physiology of their reproduction, is placed into the context of adaptive mutations, non-coding DNA, and amino acids in this first of three other brief lectures by Hopi Hoekstra.
Her lectures are virtually guaranteed to make evolutionary theorists believe that their ridiculous theories have been supported by experimental evidence of biologically-based cause and effect that the theorists think links mutated genes to morphological and behavioral phenotypes.

Alternatively, since her model organism is the deer mouse, see:
Epistasis Among Adaptive Mutations in Deer Mouse Hemoglobin
Repeated elevational transitions in hemoglobin function during the evolution of Andean hummingbirds
Natural selection for the Duffy-null allele in the recently admixed people of Madagascar
Dobzhansky (1973)

…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” (p. 127).

Does evolutionary theory need a rethink?
If you can’t understand the fact that mutations perturb protein folding and that amino acid substitutions stabilize it, you may want to take this free 10-15 hour course and become biologically informed.

After taking the course, if you do not think evolutionary theory needs a rethink, you probably are not capable of thinking about anything except ridiculous theories.