September 7, 2017 | David F. Coppedge

Deadly Effects of Single Mutations

Is this the raw material for Darwinian evolution? The genetic mutations we observe can be catastrophic.

Medical Xpress describes the tragic effects of a neurological mutation on certain afflicted children:

The extremely rare disorder is characterized by developmental regression and neurodegeneration. At first the children lead normal lives and seem identical to their age-matched peers. However, beginning at around 3 to 6 years of age, they present with neurological deterioration, gradually losing motor, cognitive and speech functions. Although the condition progresses slowly, most patients are completely dependent on their caretakers by 15-20 years of age.

Researchers at Hebrew University and Penn State found that this debilitating disease is caused by a single point mutation that represents one letter out of 3 billion letters in the human genome.

The researchers found in all patients the same spontaneously occurring, non-inherited genetic change in a gene (named “UBTF”) responsible for ribosomal RNA formation. Because of this small change, the patients’ cells are flooded with ribosomal RNA and are poisoned by it.

Another single-letter mutation is known to cause progeria, another progressive disease that turns children into old people in just 12 to 20 years.

When Does a Frog Become Deadly?

P. terribilis. Credit: Wikimedia Commons/Micha L. Rieser.

The poison dart frogs of Columbia carry a warning in their bright yellow skin: do not touch! There’s enough poison in one frog to kill 10 men at once. The poison acts by “reversing the openings of sodium channels in nerves, which prevents muscles from relaxing.” The heart muscle contracts to push blood through, but then cannot un-contract. A fatal heart attack usually results from those affected. Hunters in the jungle have learned to use this potent toxin to kill prey by dabbing it on the tips of their blow darts. These frogs are known as Phyllobates terribilis.

The toxin comes from alkaloids in the environment that the frogs ingest and store in their skin. Some researchers wondered, though, how the frogs protect themselves from their own poison.

Prior research has shown that the active ingredient in the toxin is batrachotoxin. To figure out why the dart frogs do not give themselves heart attacks when they produce the chemical, the researchers introduced five naturally occurring amino acid replacements found in the frog’s muscles into rat muscles. Doing so, the researchers report, made the rat muscle immune to the effects of batrachotoxin. The researchers then tested the amino acids individually until they found the one that was responsible for the change—N1584T. This finding overturns prior research results that suggested multiple factors were responsible for frog immunity—it shows that the immunity in the frogs comes from a single genetic mutation.

In effect, the mutation broke the effect of the toxin for the frog. This means that all the frogs without the mutation must have died, and only the “broken” frogs survived. The research is published in PNAS. A week later, Science Magazine gave helpful detail on what the single point mutation does. It breaks a working receptor:

Poison frogs produce a neurotoxin that protects them from predation. The frogs, however, run the risk of intoxicating themselves. Studying the frog neurotoxin epibatidine, which binds to acetylcholine receptors, Tarvin et al. found a single amino acid substitution. The substitution changes the configuration of the acetylcholine receptor, so that it decreases its sensitivity to the toxin. But acetylcholine signaling is essential for normal life. Expressing frog receptors in human cells revealed that different amino acid substitutions have occurred in different lineages that allow the frog to resist its own toxins while still letting target neurotransmitters function effectively.

Update 9/19/2017: Look at the tragic picture in an article on Medical Xpress. A mutation causes some babies to be born without a nose. A rare condition called Bosma arhinia microphthalmia syndrome (BAMS) is caused by mutation. “BAMS is a congenital condition in which patients are born without a nose, and often with eye defects and stunted release of sexual hormones.”

The frog story sounds like a case of natural selection, but if so, why didn’t the PNAS authors mention that? Why didn’t Phys.org mention it? Why didn’t they mention natural selection, positive selection, beneficial mutation, or anything else that would make this finding a victory for Darwin? The paper talks about the “evolution of extreme toxicity” in this frog, but the frog did not evolve into a non-frog. It just broke its reaction to the alkaloids. That may have been “beneficial” to the frog—keeping it from dying of a heart attack—but those sodium channels are there for a purpose. You don’t want to tinker with highly-functional molecular machines like that.

The Darwinians expect us to believe that random genetic mutations are the seedbed of all the progress, improvement and innovation in the living world. That’s like expecting random bullets to improve functional automobiles and trucks. As Dr Jerry Bergman said recently in a talk, “Evolution works: but in the wrong direction!” Mutations are almost always deleterious, and the “nearly-neutral” mutations that predominate without causing overt problems add up like typos in a book to degrade the genome, leading to mutational meltdown. Doesn’t intelligent design of the working machinery make a lot more sense?

 

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