Alternative splicings: epigenetics meets pharmacogenomics

By: James V. Kohl | Published on: May 27, 2015

Alternative splicing [is] …a regulated process during gene expression that results in a single gene coding for multiple proteins… [T]he proteins translated from alternatively spliced mRNAs will contain differences in their amino acid sequence and, often, in their biological functions….

See also: Alternative RNA Splicing in Evolution


It now appears that alternative splicing is, perhaps, the most critical evolutionary factor determining the differences between human beings and other creatures.

See also: From Fertilization to Adult Sexual Behavior


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.

My comment: Sex differences in other species that are due to the alternative splicings of otherwise identical genes are linked to sex differences in cancers via RNA-mediated hormone-dependent cell type differentiation.  Higher levels of estrogen are linked to ovarian cancer. Higher levels of testosterone are linked to prostrate cancer. Estrogen and testosterone levels are nutrient-dependent and pheromone-controlled in mammals. Nutrient stress and social stress probably contribute to all cancers and all other pathologies linked from metabolic networks to genetic networks.

Ovarian cancer-specific markers set the stage for early diagnosis, personalized treatments


While DNA carries all the instructions necessary for life, its actual sequence contains much more than just the genes that code for proteins. In contrast, mRNAs are complementary copies of just the genes. They carry the recipe for every protein that the cell will produce from the nucleus to the cytoplasm, where cellular machinery can read the recipe and build the corresponding proteins.
the researchers identified six mRNA isoform molecules that have the tumor specificity required for an early detection diagnostic of ovarian cancer.
These mRNA isoforms are predicted to encode proteins with unique amino acid sequences…

My comment: The link from viral microRNAs and entropic elasticity to the anti-entropic epigenetic effects of nutrient-dependent microRNAs is becoming clearer. The nutrient-dependent microRNAs control RNA-mediated cell type differentiation via amino acid substitutions.  That fact will come as a surprise to many people because scientists do not use terms consistently.
Some terms change when new information becomes available about links between protein structure and function.  You may never again see our phrase “alternative splicing techniques of pre-mRNA” in the context of an epigenetic “mechanism” linked to RNA-mediated amino acid substitutions and cell type differentiation. Some terms change because researchers need to report something new to help ensure future funding. If they can turn a phase, or invent a new term, it may confuse people. But, researchers must “follow the money.”
You may see mRNA isoforms linked to amino acid substitutions and reported as “amino acid sequences” in the context of difference in corresponding proteins. You may still see claims that proteins evolve.
What you are less likely to see is any additional claims that “…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).  You are more likely to see claims that “The expression of a gene is controlled by several other elements or factors such as microRNAs, transcribed small RNAs, and epigenetics.” Figure 6.1 (p. 114).
The claim on page 114 is made in the same book with the ridiculous conclusion about mutations on page 199. That is cause for concern.  The book is Mutation-Driven Evolution and it was published 40 years after Dobzhansky (1973) noted that “…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).
It is now clear to many serious scientists that cell type differentiation is RNA-mediated via nutrient-dependent amino acid substitutions that stabilize the organized genomes of all genera via the fixation of the amino acid substitutions in the context of the physiology of reproduction.
It is also clear that evolutionary theorists would rather have you continue to believe in their ridiculous theories than to accept the fact that their theories are horrid misrepresentations of biological facts. The facts must be considered in the context of disease prevention and treatment. The ridiculous theories must be discarded.
See also: Noncoding RNAs that associate with YB-1 alter proliferation in prostate cancer cells, which was reported as:

Team finds two new and very large classes of RNAs linked to cancer biomarker


Many small RNAs known as microRNAs already have been shown to correlate with different grades of prostate cancer and could potentially serve as biomarkers for diagnosis and treatment,” Dr. John said. “We did this study after computer models led us to hypothesize that there was a connection between YB-1 and microRNAs. What started out as a curiosity-driven experiment ended up being an exhilarating treasure hunt over four years, culminating in the discovery of two big molecular finds from human cells.

My comment: The balance of viral microRNAs and nutrient-dependent microRNAs links the microRNA/messenger RNA balance to:
1) sex differences in alternatively spliced mRNAs;
2) sex differences in their amino acid sequences;
3) sex differences in their biological functions;
4) sex differences in cancers.
Ovarian cancer biomarkers and prostate cancer biomarkers link similarities and differences in viral microRNAs and nutrient-dependent microRNAs to RNA-mediated sex difference in cell type differentiation. RNA-mediated sex differences in cell types are linked to RNA-mediated differences in all cell types of all individuals of all species via the conserved molecular mechanisms of biophysically constrained nutrient-dependent protein folding chemistry. Progress in cancer research will not come from the evolution industry or from ridiculous theories.

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