May 19, 2022 | David F. Coppedge

Mutations Conspire to Defeat Evolution

Mutations don’t just act alone.
They work in concert to decrease fitness.


A press release starts out as a celebration for Darwin. Things turn depressing below the fold.

UTM scientist reveals new insights on link between genetic mutations and biological evolution (University of Toronto at Mississauga [UTM] 16 May 2022).

Alex Nguyen Ba, an assistant professor of biology at UTM, has been trained well in Darwinism. It is his mystical idol, capable of omnipotent power. “Evolution is a force that drives all of life on this planet,” he intones. But this force, if it is a force, or maybe a farce, has a dark side and a light side. Or maybe it just has a dark side. Keep reading.

Reporter Sharon Aschaiek at UT will describe results of Alex’s work, but first, she sings the Stuff Happens chant:

In biological evolution, we know that it’s all about the survival of the fittest: organisms that develop genetic traits that allow them to better adapt to their physical environment are more likely to thrive, and thus pass down their winning genes to their offspring.

See “Fitness for Dummies” (19 June 2014) to see why this is a tautology. Or, just sing it:

Now the fit will be survivors and survivors will be fit,
And survivors will survive to prove the fitness of the fit;
O this natural selection, it’s so simple isn’t it?
‘Tis ruthless marching on.

Next, the reporter tells about Alex Ba’s devoted work to support evolutionary theory:

  • New research by University of Toronto Mississauga biology assistant professor Alex N. Nguyen Ba adds an important dimension to our understanding of how genes interact in the evolutionary process.
  • The first-of-its-kind study shows that different combinations of genetic mutations can have an impact on the evolutionary process — a finding that could benefit areas such as personalized medicine and vaccine design.
  • At UTM’s annb lab, Nguyen Ba and his team of researchers explore genetic mutations in cells and their impact on evolution using next-generation technologies.

It’s All Downhill from Here

This cheerful introduction betrays the worry to follow. Alas, Professor Ba’s work tends to upset the applecart. The combinations of 10 mutations that he uses for divination do not bring the expected vision. Is the Stuff Happens Law failing as a law of science?

  • The findings run counter to the dogma that all biological adaptation unfolds in a predictable way due to some unknown biological law.
  • Moreover, he says, it challenges the dominant view in genetic research that we should study one gene mutation at a time.

Having set out to understand evolution, Ba found some difficulties in the theory. It’s been assumed by many that you can study a point mutation to see what effect it has. This is the basis of knock-out mutation studies, where researchers break a gene on purpose to see what happens. But mutations do not work in isolation. One mutation can effect another mutation, just like a flat tire can damage an axle and cause the engine to overheat.


Alex Ba set out to study what mutations do to other mutations—an effect called epistasis. Does epistasis provide a pathway to evolutionary progress, a route to the summit of Mt Improbable in Richard Dawkins’ well-known analogy?

Adaptation can be compared to climbing a mountain. The paths taken to the various possible peaks are thought to [sic] due to successive mutations, and irregularities in the terrain can be attributed to the specific combinations of mutations acquired along the way. But how can scientists predict the route to the mountain top?

“There are huge implications if we can figure out what’s going to happen in the future for living organisms.”

To study the concerted effects of mutations on one another, Ba and his colleagues, including Christopher Bakerlee of Harvard, worked on yeast, the common microbial eukaryote. Using CRISPR, they studied all the combinations of 10 mutations—over a thousand in all. After five years of work on this, Ba found that his results were not helpful to Darwin.

Nguyen Ba completed the final year of the study at UTM, where he analyzed and interpreted the data. The study revealed that evolution frequently samples combinations of gene mutations with negative synergy between them. This acts on the yeast’s evolutionary potential in negative ways, for example, by slowing their rate of adaptation.

The findings run counter to the dogma that all biological adaptation unfolds in a predictable way due to some unknown biological law.

Instead, combinations of mutations that have accumulated through time dictate the future evolutionary potential of an organism.

Moreover, he says, it challenges the dominant view in genetic research that we should study one gene mutation at a time.

“Negative synergy” is the operative term. It can be compared to boxers or wrestlers locked in combat needing the referee to separate them, or to gimbal lock in a telescope mount, where two joints lock up so they can’t move. Obviously a yeast cell with mutations in a state of negative synergy are not going to make further progress up the imaginary fitness stairway on Mt Improbable.

Darkness on Both Sides

Eighteen years prior to this bad news, CEH reported on a paper that is like the flip side of this one. In our article “Neo-Darwinism Falsified in the Lab” (19 Oct 2004, reprinted 2020) we told how a team in Spain figured out that beneficial mutations do not help each other due to an effect they called “decompensatory epistasis.” Now, Ba’s team is saying that epistasis among deleterious mutations reduces fitness faster than individual mutations do alone. This means that the “force” that Ba claims drives all of life on this planet has a dark side and another dark side: it’s dark on both sides!

The paper on Ba’s work published in Science:

Bakerlee et al., Idiosyncratic epistasis leads to global fitness–correlated trends, Science 5 May 2022, Vol 376, Issue 6593, pp. 630-635, DOI: 10.1126/science.abm477.

The paper is filled with jargon about “idiosyncratic epistasis” and “global epistasis” and “fitness-correlated trends” (FCTs) which might be of interest to specialists. The take-home point is that nowhere in this paper do they find anything good coming out of their mutations on yeast, either singly or in combination. The yeast cells do not grow wings or eyes; there are no innovations, benefits or improvements among these poor damaged cells that the evolutionary biologists can say increased their fitness. Instead, they make the following admission, which other evolutionists should sit up and notice.

However, this distribution of FCT directions is important because it may underly the ubiquitous trend of declining adaptability observed across laboratory evolution experiments. The observed bias toward negative trends may arise from asymmetries in the average sign of epistatic interactions between mutations away from extant high-fitness genotypes relative to their reversions, which theory has predicted should arise from idiosyncratic interactions. In addition, choosing polarizations at random will lead to more negative than positive FCTs across the full parameter space (see the extended discussion in the supplementary materials).

Don’t miss that statement: “the ubiquitous trend of declining adaptability observed across laboratory evolutionary experiments.” That’s observation. That’s science. Thousands of mutations on fruit flies have not produced a better fruit fly.

Update 5/19/2022: Science just published a related paper by Park et al., “Epistatic drift causes gradual decay of predictability in protein evolution,” Science 19 May 2022, Vol 376, Issue 6595, pp. 823-830, DOI: 10.1126/science.abn6895.
Like Ba’s paper, the authors cannot point to any innovations, benefits or improvements wrought by mutations. This paper reinforces natural selection’s reputation as a manifestation of the Stuff Happens Law—the antithesis of science.

The effects of mutations were highly contingent on a dense network of epistatic interactions. There were mutations with both short and long memory length, but the average rate of epistatic change was generally constant. The landscape of potential and actual interactions is thus constantly shifting at a rate that can be known, but the direction of the change is contingent on evolutionary history and becomes unpredictable after a time.

Back to the other paper. Ba offers the following counsel at the end of the press release:

“We’re showing that in order for us to have a full understanding of how genes actually behave,” says Nguyen Ba, “the combinations of mutations are likely to be very important.

From this study and the 2004 one, it appears that evolution can only climb down Mt Improbable in the dark.

Yes, that is likely to be very important.

Advice to readers of scientific papers on evolution: One usually has to work past the triumphant hype about “understanding” the “evolutionary process” to get to the empirical meat of the research. In the cartoon below, don’t take a picture of all the king’s horses and all the king’s men while they are celebrating and cheering their hero. Wait till Humpty Darwin starts losing his balance.

Humpty Darwin sits on a wall of foam bricks held together by decayed mortar. Cartoon by Brett Miller commissioned for CEH. All rights reserved.




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