Mark: Are Mutations Random?

(S. Joshua Swamidass) #41

For the record I’m glad that @T_aquaticus is doing this so I don’t have too.

The larger picture is important too. It’s clear there are large disagreements here. Perhaps an important strategy, to break the pattern if nothing else, is to identity points of common ground.

(S. Joshua Swamidass) #42

Meyer and I, surely, agree on many things. Perhaps this is one of them. I suspect we think so for different reasons.


I would politely disagree. I have been very upfront about the limitations inherent in the scientific conclusions which prevents science from making any ontological claims about randomness. There is plenty of room for a joining of the scientific definition of random and a diverse set of theological and philosophical views. In the end, mutations are no different than any other process we see in nature, be it thermodynamics or quantum mechanics.


[quote=“Argon, post:35, topic:1548, full:true”]
I really enjoy reading Arlin Stolzfus. He’s studied computational biology with W. Ford Doolittle and works in the areas of evolution, mutation and phyloinformatics. He’s also very knowledgeable about the history of evolutionary theory and the Modern Synthesis. Here is his review of Shapiro’s book.

I feel like this review supports Shapiro and Marshall in regard to their perspective on randomness:

“The second vital premise is that the outcome of the mutation process is not random in the sense that neo-Darwinism proposes. We have to abandon this doctrine if some substantial fraction of mutations are not random, and Shapiro has clearly shown that”

Can we agree with his statement that mutations are not random in the sense “that neo-Darwinism proposes”?

@sygarte also reviewed the book and seems to make similar points but Garte, to the best of my knowledge, supports an EES.


Theories don’t make statements. What we would need to see are statements made by scientists and see how those compare to what Shapiro is saying.

(George) #46


Why cant you agree with the sentence posed by Mark?.. at least from the perspective of Christians (though admittedly you are not one yourself).


Because I don’t agree that scientists are saying that mutations are random with respect to rate, genomic position, or time. I think that quote mischaracterizes what the scientific consensus is.

(George) #48


Then i think you are missing the point of Mark’s question!

Im starting to think you add a portion of the bizarre to these discussions.


Shapiro proposes that mutations are not random with respect to rate, genomic position, or time. From my reading, the modern theory of evolution proposes that mutations are random with respect to fitness. Shapiro never demonstrates that mutations are not random with respect to fitness, so I don’t see how Shapiro has “clearly shown” that mutations are not random in the way that the modern theory of evolution proposes.

(George) #50


The quote above implicitly mentions Shapiro…

But the question is about the neo-Darwinist view of randomness… not Shapiro’s view of randomness.


And the answer is that the neo-Darwinian view of randomness with respect to fitness was not shown to be wrong by the evidence Shapiro points to.

I mentioned the work by the Lederbergs, Luria, and Delbruck earlier. This is important. DNA hadn’t been discovered when they determined that mutations were random with respect to fitness. None of their work looked at changes in the rate of mutations, genomic position of mutations, or anything else Shapiro tries to argue for. Their conclusions pointed to the independence of fitness and variation. From the very start the neo-Darwinian view was that mutations were random with respect to fitness.


It might be helpful to discuss a specific case where scientists thought they may have found evidence of non-random mutations.

What happened is they knocked out parts of a lactase gene responsible for lactose metabolism. They starved these bacteria in the presence of lactose, and in response they saw an increase in the number of mutants who recovered lactose activity. On the face of it, it appeared that the presence of lactose increased the rate at which mutations recovered lactase activity. If the presence of lactose directly increases the rate at which the bacteria specifically recovered lactase activity then those would be mutations that are non-random with respect to fitness.

However, the story took a different turn. As it turns out, when E. coli are starved it causes DNA damage. The bacteria respond to DNA damage by turning on genes that increase recombination and mutations, which is called the SOS response. These mechanisms didn’t specifically increase the mutations in the lactase gene, they increased the rate of mutations throughout the entire genome. Therefore, it was finally concluded that these mutations were random with respect to fitness afterall.

This is why I say that Shapiro is misleading people. Increases in the rate of random mutations is not an example of non-random mutations, and yet he tries to act as if it is.

(Joshua Hedlund) #53

I’m not sure how coherent this will be but consider it a chance to work out some thoughts in public. I think you two are getting to the heart of the matter. Operations that are analogous to running a particular slot machine faster, things like increasing recombination and mutations in response to damage… while on the one hand I understand why Joshua and T_aquaticus are insisting that the mutations are technically random, I also understand why on the other hand others like Marshall are intrigued by the idea that they are non-random with respect to rate or position or what have you…

I suppose whenever I heard the neo-Darwinists growing up as an interested layman it never even crossed my mind that those sorts of “non-random” respects were possible, and they seem much more “cool” (to use a very subjective word) than the impression of random mutations I had previously had… (I will leave it to the reader to determine whether that was my fault or theirs.) Perhaps rather than hint at some sort of vague “intelligence” like Marshall or Shapiro, I might propose the phrase “artificial intelligence”, since those sort of actions at least seem to me somewhat analogous to the way a computer program might utilize “randomosity” in pursuit of a goal, without insinuating consciousness on the level of the cell or anything like that.

Now from there perhaps we could discuss if that perceived “artificial intelligence” was bootstrapped evolutionarily from random mutations, and whether that has any implications on whether or not it was in some sense designed / determined / driven / guided, whether in more of a Simon-Conway-Morris sense or more of a Perry-Marshall sense or more of a something else sense, but I feel like need to learn more and organize my thoughts further before attempting any contribution on that front.


I also think those findings are intriguing. There may have been selection for mechanisms that increase the random mutation rate in environments that cause stress. That is of great interest to scientists. Any mechanism that influences the process of mutagenesis is worth studying.

What I and others are objecting to is the misrepresentation of these findings, not the importance of these findings.

(S. Joshua Swamidass) #55

I am also objecting to the use of several terms to and concepts in relation to modern understanding:

  1. Darwinism and Neo-Darwinism is not current evolutionary science

  2. There is no such thing as “totally random” or “randomness without any patterns”, so finding a pattern in mutations does not prove it isn’t random.

  3. Scientists are not close minded about the underlying science here, but object to being called close minded.

  4. EES is not a new paradigm of evolution.

I could go one. This is an argument about naming things by people who want to get famous for renaming things others discovered.

(George) #56


So it is your intention to be constantly discussing or defending Neo-Darwinism … when the mission of this site is to emphasize God-Governed Evolution?


I wasn’t aware that those were contradictory goals.

(Blogging Graduate Student) #58

The most compelling case that I think I’ve seen so far for anything resembling mutations that are non-random with respect to fitness (biased towards increased fitness) are outlined in these 2 papers:

To roughly summarise their results: cells growing on glycerol are more likely to experience an insertion of IS5 specifically upstream of a glycerol metabolism (glpFK), which acts as a promoter to upregulate glycerol metabolism. The mechanism for this is that glycerol binds to a repressor of the operon (glpR). This is what activates the operon in the first place by stopping glpR from binding to a control region. It turns out that having glpR bound to that control region stops IS5 insertions, so removing it (by any means) increases the prevalence of IS5 insertions. Another factor is the presence of cAMP: less cAMP = less binding of a cAMP complex to that control region which exposes it to even more to IS5 insertion.

Basically the presence of glycerol and absence of cAMP causes a very high insertion rate of IS5 into the control region to activate the operon. This can be advantageous in conditions where glycerol and a cAMP depressing toxic substance (such as 2-deoxyglucose, synthesised naturally by many organisms as a defence mechanism) are present simultaneously.

It’s also possible that this insertion is reversible, so the whole thing could be a temporary solution to the problem. This in effect makes it just like a “normal” mechanism of genetic regulation, little different in concept to any other operon that’s activated in response to a particular molecule. In other words, it’s readily evolvable. It would be striking if this kind of temporary regulation really was caused by an insertion and subsequent deletion of a particular transposon in a particular place. Although I don’t think this example, if accurate, would do much to make us reconsider the fundamentals of evolution, it is interesting.

(George) #59


How could you have missed that?

The first thing creations talk about is the issue of design. This issue is immediately neutralized by the obvious reliance of Christians on God’s active role in creation… whether its in 6 days or over millions of years!

Your constant recursion to Godless evolution being “kinda non-random” is not a relevant refutation.


This conversation has helped me see things a lot clearer. I’m still about where I was where we started but more confident. @Swamidass, as far as I can tell, the difference between you and the EES is one of semantics and emphasis.

@swamidass, @T_aquaticus, @Argon, how do you interpret Dobzhansky fruit fly experiments? And Ayala’s follow up experiments? If Ayala’s produced some improvements while Dobzhansky’s didn’t produce any, and the improvements in Ayala’s were regarding radiation resistance, would the slot machine analogy really work? Same with epigenetics, and other similar mechanisms. If mutations are like a slot machine then shouldn’t an equal amount of fruit flies come away with legs coming out of their heads as come out with radiation resistance?

As a layman in the science realm, I admit I am ONLY referencing Marshall’s references to these experiments and maybe there’s something I’m not understanding.