December 14, 2006 | David F. Coppedge

Mutations Accelerate Each Other’s Damage

As reported in our 10/14/2004 entry, mutations do not work in isolation; even the good kind usually conspire against the host.  This fact has been largely ignored by neo-Darwinists.  Some researchers at the Weizmann Institute in Rehovot, Israel, writing in Nature,1 tested the interaction of mutations (epistasis) on proteins.  They found, in short, that harmful mutations usually accelerate the loss of fitness above what would occur in isolation.  Some organisms exhibit robustness against mutations, though, as in well-known cases of antibiotic resistance.  The team tested the robustness of E. coli while mutating a gene for a lactamase (TEM-1) that confers some resistance to ampicillin.  They found that, at best, the organisms could hold out at a threshold level of fitness only temporarily.  Beyond the threshold, death was speedy and inevitable.  This was even after they removed the bad mutations:

Subjecting TEM-1 to random mutational drift and purifying selection (to purge deleterious mutations) produced changes in its fitness landscape indicative of negative epistasis; that is, the combined deleterious effects of mutations were, on average, larger than expected from the multiplication of their individual effects.  As observed in computational systems, negative epistasis was tightly associated with higher tolerance to mutations (robustness).  Thus, under a low selection pressure, a large fraction of mutations was initially tolerated (high robustness), but as mutations accumulated, their fitness toll increased, resulting in the observed negative epistasis.  These findings, supported by FoldX stability computations of the mutational effects, prompt a new model in which the mutational robustness (or neutrality) observed in proteins, and other biological systems, is due primarily to a stability margin, or threshold, that buffers the deleterious physico-chemical effects of mutations on fitness.  Threshold robustness is inherently epistatic—once the stability threshold is exhausted, the deleterious effects of mutations become fully pronounced, thereby making proteins far less robust than generally assumed.

Their study also casts doubt on the ultimate survivability of so-called “neutral” mutations.  These initially have no obvious effect on the fitness of the organism.  This may be due to backup copies of a gene, suppressors of the mutated gene, and other mechanisms the cell uses to mask the damage.  Eventually, however, the threshold is exceeded and the system collapses just as rapidly as a cell toppled by interacting harmful mutations.
    The authors of this study gave no indication that beneficial mutations can add up and help an organism.  In fact, they failed to say anything about evolution that would provide hope for progress.  By contrast, they offered a “new model” that sounds distinctly anti-evolutionary: cells are programmed to hold off the damage of mutations as long as they can, but will ultimately collapse under a mutational load.  They concluded that “proteins may not be as robust as is generally assumed.”  Their real-world experiment on bacteria showed robustness to mutations only to a certain point, then everything raced downhill:

Thus, theory and simulations have predicted a tight correlation between robustness and epistasis.  Our work provides an experimental verification of this correlation and proposes a mechanism that accounts for it.  Our model implies that any biological system that exhibits threshold robustness, or redundancy robustness, is inevitably epistatic.  In such systems, mechanisms that purge potentially deleterious mutations, such as recombination (through sexual reproduction and other mechanisms) are of crucial importance, as they help to maintain this threshold.  In this way, recombination, threshold robustness and negative epistasis may be interlinked—each being an inevitable by-product of the other.

They seem to be saying not only that mutations are not sources of positive fitness gains, but other proposed mechanisms like recombination are only stopgap measures to protect against the death spiral that would result when “randomly drifting proteins” gang up (negative epistasis) to cause a terror attack in the organism.

1Bershtein et al, “Robustness-epistasis link shapes the fitness landscape of a randomly drifting protein,” Nature 444, 929-932 (14 December 2006) | doi:10.1038/nature05385.

It is extremely important that followers of the creation-evolution debate understand this story and the earlier one (10/14/2004), because they cut to the heart of Darwinist claims that mutations and natural selection can create brains out of atoms given millions of years.  This is where the rubber meets the road: can mutations and recombination under selection act in concert to produce evolutionary progress, including wings and eyes and sonar and powered flight?  Complex systems need an explanation at the genetic level.  The modern synthesis of evolutionary theory (neo-Darwinism) maintains that mutations are the source of evolutionary novelty, and that natural selection preserves the rare beneficial mutations in a cumulative way.  This is the machine room from which “endless forms most beautiful” (06/29/2005) emerge without a Designer.  Two scientific papers reported here, that would likely be little noticed otherwise, have essentially falsified neo-Darwinism in the lab.  Theory and experiment both show it does not work.
    In the previous entry (10/14/2004) we likened the situation to a victim held up by robbers but protected by guardian angels.  The bad news was that the robbers either shoot each other or shoot the victim simultaneously, and the guardian angels fight each other instead of helping the victim.  It’s like a Murphy’s “Non-Reciprocal Laws of Expectations” that state, (1) Positive expectations produce negative results, and (2) Negative expectations produce negative results.  The neo-Darwinists have put all their hope in positive expectations, but real-world experiments show that mutations do not and cannot add up for good.  They conspire for bad!  Only the built-in safety mechanisms in the cell hold off mutational catastrophe.  This same lesson should have been learned from the important 03/17/2003 entry almost four years ago; presumed benefits actually cause “slippage on the treadmill” to keep the organism, at best, just running in place.
    Another analogy may illuminate what this new outwardly dry, boring, technical paper said.  Picture a large, well-run factory with numerous modern systems for safety, backup and security.  Along comes a motley gang with no plan other than to wreak havoc at random.  Some are blocked by the entrance controls.  Those that get inside start overturning tables, knocking out factory workers, setting off alarms and creating general mayhem.  The security systems each come into play as planned, trying to isolate the damage, restore backups, and start the redundant processes.  Workers scramble to copy off the important data to other sections of the factory where the work can continue.  Security guards manage to neutralize some of the attackers, but more keep coming in.  Some gangsters plug the real workers then steal their lab coats and badges, wandering around to do their harm by stealth.  To an outsider, it may not be apparent that anything is wrong – for awhile – because the factory continues to function; supplies come in, goods go out.  In time, however, the best-prepared factory may not be able to carry on.  Fires are set at random.  Automatic sprinklers respond as designed, but now they have damaged the computers.  Gangsters pull fire alarms here and there, confusing workers who don’t know whether to ignore them or run outside.  Security forces are eventually overwhelmed.  Backup systems are damaged as soon as they are brought online.  It’s too much; the factory implodes in a catastrophe, and everything shuts down.
    If this is really the way mutations work in a cell, it should be obvious to everyone that trusting any random mechanism to produce order is a vain hope and supreme folly.  This, of course, is what anti-Darwinists have been maintaining since 1859.  That it would take two research teams with no ties to creationist organizations or the intelligent design movement, published in two of the most adamantly anticreationist scientific journals in the world (PNAS and Nature) to finally figure this out should be of great interest to historians and sociologists.  What is it about Darwinian faith that generates negative epistasis against common sense?
    Evolutionary theory is coasting downhill on a dead-end track with no fuel in the engine, while the passengers are being served cheese and wine, not knowing anything is wrong.  Creation-Evolution Headlines is like the tattler running down the aisles warning everybody about bad news only the engine crew is aware of, despite the pleasant announcements on the intercom.  We think the customers who paid for the trip deserve to be told the truth: despite how smoothly things appear to be running, they just got sold a dead-end trip to destruction.

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Categories: Cell Biology, Genetics

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