PLOS Genetics on non-random mutations

Interesting open-access review from PLOS Genetics, “What is mutation? A chapter in the series: How microbes “jeopardize” the modern synthesis”. From the abstract:

Mutations drive evolution and were assumed to occur by chance: constantly, gradually, roughly uniformly in genomes, and without regard to environmental inputs, but this view is being revised by discoveries of molecular mechanisms of mutation in bacteria, now translated across the tree of life. These mechanisms reveal a picture of highly regulated mutagenesis, up-regulated temporally by stress responses and activated when cells/organisms are maladapted to their environments—when stressed—potentially accelerating adaptation. Mutation is also nonrandom in genomic space, with multiple simultaneous mutations falling in local clusters, which may allow concerted evolution—the multiple changes needed to adapt protein functions and protein machines encoded by linked genes. Molecular mechanisms of stress-inducible mutation change ideas about evolution and suggest different ways to model and address cancer development, infectious disease, and evolution generally.

This view of “highly regulated mutagenesis, up-regulated temporally by stress responses and activated when cells/organisms are maladapted to their environments” is very friendly to a teleological perspective, where evolution is seen as a biological function, rather than something that just happens to happen to inefficiently replicating organisms.

Indeed it is. Fearfully and wonderfully made, we are. I wonde how houch of it is hype, though.

Which parts do you think might be hype? That the phenomenon of regulated mutagenesis actually exists (and isn’t, for example, a case of stressed cells/organisms diverting ressources away from ensuring fidelity in replication), or that the phenomena accounts for much of evolution?

“Regulated mutagenesis” is a very fancy name for stress-induced increase in mutation rate. Has this been documented outside bacteria?


I don’t see how the phenomena described in the PLoS Genetics article are particularly friendly to a teleological perspective. Collectively, the mechanisms are tantamount to different approaches towards carpet bombing a genome (or large swaths thereof), with the hope or expectation that among the collateral damage will be a change that may be beneficial under stressful conditions. This doesn’t sound like very sound design to me. (But, on the other hand, maybe “Bomber” Harris is a role model of sorts for teleologists?)

Also, I think it helpful to recall - Darwin’s theory of evolution rests on two piers. One is that all life shares a common ancestry. The other is that the different forms of life we see derive from descent with modification, whereby natural selection acts on heritable variation. The mechanisms summarized in the PLoS Genetics paper are all about increasing heritable variation. As such, they are quintessentially Darwinian.


It’s not interesting at all. There’s a reason why “jeopardize” is in scare quotes.

From the conclusion:
“Stress-induced mutation mechanisms, first discovered in bacteria, challenge historical assumptions about the constancy and uniformity of mutation but do not violate strict interpretations of the Modern Synthesis.”

I think the joke’s on you.

Did you ever come up with a design hypothesis that explains the fundamental difference between start and stop codons?


I don’t see how increasing the random mutation rate fits with your view. Can you explain?

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From the article:

First off, the authors didn’t reference any other literature for this supposed assumption. In my reading, “chance” simply meant that the processes that produced mutations were blind to the needs of the organism. If someone gambles at casinos more on the weekends than during the week, no one says that gambling is not chance because time spent gambling is not uniform through time.


Of course. I tentatively propose that prebiotic Earth was seeded with engineered cells. As any entity that reproduces with heritable variation will undergo evolution through natural selection, it stands to reason that the engineers would expect evolution to be a factor in this designed biosphere. At this point, it would make sense for the engineers to design life in such a way that it took advantage of the full potential of natural selection and evolution.

One such way to take advantage of evolution would be to employ regulated mutagenesis to overcome challenges in the environment. If an organism found itself facing a challenge it wasn’t adapted to overcome, it could up-regulate its mutation rate, increasing the chance that the right mutation would come along.

As bacteria are the most diverse and abundant cellular lifeforms on Earth, it would be no mean feat even if regulated mutagenesis was restricted to them. But as the review makes clear, evidence of regulated mutategenesis has also been found in yeast and even in multicellular eukaryotes like plants, flies, and humans.

See my reply to @T_aquaticus above: A sensible engineer would harness the creative power of evolution.

In saying that regulated mutagenesis doesn’t sound like sound design, are you saying that it doesn’t have an adaptive value? And if so, why did cells go through so much trouble evolving the genetic programs responsible for regulating mutagenesis, such as the SOS response (described in the review)?

I never said otherwise.

John @Mercer’s reply is a good example of what happens when ID critics go into “debunking mode”. Instead of reading for understanding and engaging with the (rather modest) point of my post, he chooses instead to:

  1. Fight strawmen, acting as if I was arguing that regulated mutagenesis was incompatible with the Modern Synthesis.

  2. Nitpick areas with which to disagree, such that even me calling a review “interesting” has to be negated. If I had written that it was a nice day out, I’m sure Mercer would have been vigorously arguing that it was in fact a horrible day out.

  3. Try to derail the thread by dredging up completely unrelated issues from other threads, where he thinks I owe him an explanation.

In this case, it would be an increase in the number of chance mutations, correct?

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Of course. I don’t deny the creative power of random mutations and natural selection. I’m an evolutionist.

It seems that you have the cart in front of the horse. You are finding out how biology functions, and then inventing reasons why it would be consistent with your theory. I would be much more impressed with risky predictions than vague post-dictions.


@Krauze, don’t you think it possible that the title you gave in the opening post might give one exactly that impression?


That’s impressive, Krauze. Every one of your three points is false!

No straw man. I am directly taking issue with your claim that the review

No, my disagreement with your claim is about the review’s alleged friendliness to your teleological perspective. If that’s a nitpick, then your citation of it was a nitpick. I’m also taking issue with your misleading title.

Now you’re making a claim about what I THINK, and a patently false one at that!

I don’t think you owe me an explanation, I think that you are intellectually incapable of coming up with one. That’s a very big difference.

An Intelligent Designer wouldn’t need to.

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That’s very unlikely, since @Krauze can’t even come up with the vaguest of post-dictions for the functional difference between start and stop codons, after stating that the stop codon design was an example of the teleology he champions:

Krauze doesn’t seem to have much enthusiasm for considering facts that bring that last sentence into focus.

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What I think is that a clever engineer should be able to build into a system ways by which a stimulus can lead to specific and targeted alterations suited for the task at hand, without the collateral damage associated with the stress-associated random mutagenesis that we see.

There are numerous hypothetical approaches to designing adaptive mutagenesis, but the ones we see in biology seem much less efficient (or teleological) than other designs.

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I think that the presence of these mechanisms in multicellular eukaryotes, particularly those with long generation times, actually argues against the claim. It’s unlikely that increased mutation rate due to starvation is going to benefit either the germ line or any actual zygotes. The main effect of starvation would be to reduce or prevent embryogenesis, not to make embryos with high numbers of germ line mutations. Therefore if it’s adaptive, it isn’t adaptive for the purpose of evolvability.

Expecting that engineers want their designs to be robust and able to overcome the challenges of the environment isn’t an ad hoc expectation. It flows naturally from what we could term “good design” principles.

But let’s see what this teleological perspective leads us to expect. Remember, I’m only suggesting that the original population of cells was designed. That means that if a particular structure found in extant life was designed, it would have been present in an ur-state in the first cells, from which it has diversified and become modified by evolution. For example, antifreeze proteins that evolved in the Antarctic notothenioids 10-14 million years ago would be a poor candidate for design.

This means that I would expect the phylogenetic distribution of the machinery required for regulated mutagenesis, such as the SOS response, to show that the system traces back to an ur-state in the first bacteria. And indeed, both recA and lexA, which play key roles in the regulation of the SOS response, are practically universal in bacteria. And those bacterial groups which lack them are thought to have secondarily lost them. This points to the existence of an original SOS response core, which evolution has then unfolded into the systems we see today.

Distribution of the lexA gene across the bacterial domain, based on the phylogenetic distribution derived from RecA protein sequences (Eisen,1995). Light grey areas enclose phylogenetic groups and dark grey areas indicate the presence of lexA . Filled circles denote species that have undergone substantial genomic reduction. From Erill, Campoy & Barbé, 2007

This expectation of an ur-state stands in sharp contrast to the expectations of the ateleological view, in which every organism with structure X is descended from an organism without that structure, all the way back to the first replicator.

Scientists estimate that Earth has about one trillion microbial species, with 98 percent yet to be discovered. In other words, there are lots of opportunities for discoveries of bacteria that represent this supposed pre-SOS response state, dashing my teleological expectatins.

One final note: I don’t have a theory. I have a conjecture, which I’m trying to flesh out in my spare time.

The title of the review? I linked to the review and told people of its title. The title of my own post “PLOS Genetics on non-random mutations” focused on what I found interesting about the article, and I wrote nothing about whether or not I thought regulated mutagenesis was consistent with some interpretation of the Modern Synthesis.

It really says something about the hair trigger that some ID critics seem to have that merely mentioning the title of a review one is discussing opens one up to accusations that one is misrepresenting the contents of the review.

I suppose one could in principle equip cells with a sort of molecular computer which could analyse new challenges, predict the protein that would be required to face the challenge and which mutations would result in that protein, and induce the desired mutation. But I think the resources required to maintain such a computer would be more taxing on the cell that any benefit gained from it.

A better solution, in my view, is to make life itself the computer. Have lots of cells experiment with solving a problem and let the succesful attempts spread by “cross-talk” between cells, i.e. horizontal genetic transfer and exchange of plasmids.