Pathogenic variants that alter protein code often disrupt splicing

Approximately 10% of exonic mutations altered splicing, mostly by disrupting multiple stages of spliceosome assembly. We present a large-scale characterization of exonic splicing mutations using a new technology that facilitates variant classification and keeps pace with variant discovery.

Assay of nearly 5,000 mutations reveals roots of genetic splicing errors

“Splicing errors can be very deleterious because instead of just changing one amino acid [the building block of a protein], it can take out a stretch of 40 or 50 amino acids,” he said.

All energy-dependent alternative splicing must be linked to the physiology of reproduction by amino acid substitutions in supercoiled DNA that protect all organized genomes from virus-driven energy theft and genomic entropy.

See for example: Difference in Plumage Color Used in Species Recognition between Incipient Species Is Linked to a Single Amino Acid Substitution in the Melanocortin-1 Receptor

Assuming that the signals used in species recognition are also used in mutual mate choice, our results indicate that a single amino acid substitution contributes to speciation.

Genome divergence and diversification within a geographic mosaic of coevolution

Our results further characterize a striking example of coevolution driving speciation within perhaps as little as 6000 years.

See also: Past 5,000 years prolific for changes to human genome

Of 1.15 million single-nucleotide variants found among more than 15,000 protein-encoding genes, 73% in arose the past 5,000 years, the researchers report.  164,688 of the variants — roughly 14% — were potentially harmful, and of those, 86% arose in the past 5,000 years.

The time has come for all theorists to choose between pseudoscientific nonsense about mutations and evolution during millions of years or natural selection for energy-dependent codon optimality, which is linked to all biodiversity by the physiology of reproduction and what is known about supercoiled DNA.

Supercoiled DNA prevents the virus-driven degradation of messenger RNA, which is linked to all pathology in all living genera.

Nature did not invent supercoiled DNA, which protects all organized genomes from virus-driven energy theft and genomic entropy. Nature did not engineer anything.

See for contrast: Nanoscale-length control of the flagellar driveshaft requires hitting the tethered outer membrane

…bacteria have evolved elegant and robust regulatory mechanisms to ensure that flagellar morphogenesis follows a defined path, with each component self-assembling to predetermined dimensions.

Reported as: How nature engineered the original rotary motor

Because the flagellum is tied to a bacteria’s ability to move, an understanding of the controls on the flagellar system could help researchers learn how to immobilize harmful bacteria, and to hamper the flagellum-like systems that some bacteria use to infect host cells.

The claim that bacteria evolved a self-assembly mechanism does not fit into the context of any claim ever made by serious scientists who understand that the nutrient-dependent pheromone-controlled physiology of reproduction biophysically constrains any molecular mechanisms that link energy to controls on the flagellum. Researchers who make claims about self-assembly or the weekend resurrection of the bacterial flagellum in P. fluorescens reported in Science (Feb 2015) are not serious scientists. They are evolutionary theorists.

See: Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system

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