Quantitative analysis of RNA-protein interactions on a massively parallel array reveals biophysical and evolutionary landscapes

RNA-protein interactions are tethered to DNA via ultra-high-throughput measurement of the RNA-protein interactions that link amino acid substitutions to cell type differentiation. Differences in affinity are often driven by sequence-specific changes in both association and dissociation rates that rapidly link bio-physical constrained RNA-mediated protein folding to models that provide “…generalizable insight into the biophysical basis and evolutionary consequences of sequence-function relationships.”

This is the generalizable insight that is most likely to link the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man via what is currently known about the nutrient-dependent pheromone-controlled physiology that links RNA-mediated amino acid substitutions to cell type differentiation via the bio-physically constrained chemistry of protein folding.

Given this generalizable insight, my model of nutrient-dependent amino acid substitutions can be compared to a theory 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) — Nei (2013)

Theories about the role of mutations and reports of evolution from experiments on Escherichia coli can be addressed in the context of biological energy and the conserved molecular mechanisms that link “…MS2 from low- to high-affinity hairpins via widespread molecular epistasis and a long-hypothesized, structure-dependent preference for G:U base pairs over C:A intermediates in evolutionary trajectories.”

See also: The majority of transcripts in the squid nervous system are extensively recoded by A-to-I RNA editing

Excerpt: Moreover, highly edited sites within conserved domains tend to recode to amino acids that occur frequently in other species at the same position (Figure 4–figure supplement 3), suggesting selection towards functional substitutions and against deleterious ones.

My comment: This is what is expected when nutrient uptake leads from RNA-directed DNA methylation and RNA-mediated amino acid substitutions that differentiate cell types in all cells of all individuals of all species. The article adds even more support for my model in the context of RNA editing.

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