In the comments of my August 17th post, Learning mutation bias, Arlin Stoltzfus, Perplexed in Peoria, and I have been discussing the meaning and implications of his work. Since this conversation is buried in a month-and-a-half old post, I thought I would bring it up to the front of the blog for more exposure. Below I will quote the fairly long discussion in full. As Perplexed notes, the conversaion may be hard to follow if you have not read Stoltzfus’ research articles or his blog series at Sandwalk, The Curious Disconnect: The Mutationism Myth.
After my post and Arlin’s first comment, I asked, “By the way, would you recommend reading JL King’s “The Role of Mutation in Evolution”? Is it still relevant?”
I can summarize what’s relevant about King’s paper. Mainly its relevant for historical reasons, to remind us how much the new “molecular” view diverged from the view that Mayr, et al worked so hard to establish.
In the earlier paper that co-proposed the neutral theory, King and his co-author Thomas Jukes (1969) argued that the observed correlation between a) frequencies of amino acids in proteins and b) numbers of codons assigned to an amino acid in the genetic code was evidence for neutral evolution. In a non-neutral view, they said, “one particular amino acid will be optimal at a given site in a given organism, and it matters little whether there are six possible codons (as there are for serine) or only one (as there is for methionine).”
However, in his 1971 article, King recanted and said that this was not evidence for neutral evolution, because the same pattern could be seen under a lucky mutant view of adaptation in which “the adaptive mutations which are fixed are those which arise first and are not lost”. If so, then:
“Suppose that, at a given time, there are several possible amino acid substitutions that might improve a protein, and among these are changes to serine and to methionine; serine, with its six codons, has roughly six times the probability of becoming fixed in evolution. Once this has occurred, the mutation to methionine may no longer be advantageous. Ultimately, the amino acid frequency composition of proteins will reflect the frequencies at which the various amino acids arise by mutation, which in turn depends on the genetic code and DNA nucleotide frequency composition.”
Thus King said that the correlation was not evidence against “adaptation”, but only evidence against a deterministic model in which selection picks out the optimal genotype from the gene pool. Maynard Smith (1975) picked up on the significance of this, repeating King’s argument and concluding:
“If we accept the selectionist view that most substitutions are selective, we cannot at the same time assume that there is a unique deterministic course for evolution. Instead, we must assume that there are alternative ways in which a protein can evolve, the actual path taken depending on chance events. This seems to be the minimum concession the selectionists will have to make to the neutralists; they may have to concede much more.”
What’s shocking about this whole episode is how this remarkable “concession” was never acknowledged. What King and Maynard Smith are accepting is a stochastic “lucky mutant” view of evolution, as distinct from the deterministic view in which selection picks the best codon from all the alternative codons in the “gene pool”. King made this distinction very clear in his paper, though he did not refer back to the mutationists.
The alternative, in 1971, was that, if a gene has codon X at position Y, this is because codon X is the best possible codon for position Y. That is what being a neo-Darwinist meant in 1971. No one actually adopts that view today, although its often hard to tell because the language has not changed. “Selectionists” today write triumphantly as though they had won the debate over molecular evolution. Nothing could be further from the truth.
Were Jukes and King predicting codon bias in their 1968 paper?
So is the view adopted by King and Maynard Smith basically what Rokyta et al. were testing in their adaptive walk experiment? That the most beneficial mutation isn’t necessarily the one that gets fixed?
This seems like an example of where many biologists accept these ideas but it has yet to enter the verbal conception of evolution. It is weird (but cool) how old these ideas really are. Does someone like Dawkins not agree with these ideas?
Perplexed in Peoria:
Arlin: What’s shocking about this whole episode is how this remarkable “concession” was never acknowledged.
What, exactly, should have been acknowledged and who, exactly, should have acknowledged it? As Kele points out, beginning from roughly this point in time (1975), most theorists came to agree not only that the course of evolution is not deterministic, but also that most substitutions are neutral
Kele’s readers who have not yet discovered The Curious Disconnect are probably puzzled regarding what is at stake in this dispute.
“What, exactly, should have been acknowledged and who, exactly, should have acknowledged it?”
I don’t know– I’m not interested in what folks “should” do. I said it was remarkable that such a critical change in thinking could happen, yet not be widely known.
But I would say that, in fact, a profound change in thinking did NOT happen, but only a muddled compromise to the effect that evolution is “not deterministic”, which barely scratches the surface.
Let’s review. Then we can ask if this is “puzzling”.
According to King, one way of thinking about why we observe some pattern or feature goes this: there is some set of possible codons at a site, and selection chooses the best one based on the encoded amino acid, regardless of whether it can be encoded by 1, 2, 3, 4 or 6 codons. King says that this way of thinking has a justification according to neo-Darwinian assumptions (the “gene pool” and so on), and indeed, he says its still valid when applied to “phenotypes”.
The alternative, according to King, is that change just keeps on happening and happening at a rate depending on the mutation rate AND the chance of acceptance, so that the steady-state distribution of amino acids will reflect codon number due to an effect of mutation (more codons in a set, more mutational pathways to that set), even when all the changes represent *selective* (not random) fixations.
We need a third view to cover mainstream thinking in molecular evolution, which presents mutational explanations as “neutralist” hypotheses, assuming implicitly that mutational effects only happen under the condition of neutral evolution. This view is consistent with the idea that evolution is “not deterministic”. Its consistent with the Modern Synthesis view of mutation as a “weak force” unable to “oppose” selection. But conceptually its a muddle, neither fish nor fowl.
Is that puzzling?
Thanks for the responses.
Kele asks: “So is the view adopted by King and Maynard Smith basically what Rokyta et al. were testing…? That the most beneficial mutation isn’t necessarily the one that gets fixed?”
Yes and no. Clearly I’m not getting my message through. If you’ll pardon me for saying it, my frustration is the sense that folks keep taking what I’m saying, which is rich in implications, and throwing out the interesting bits, and transforming it into (what seem to me to be) rather lame and impotent expressions of “not”: evolution is “not deterministic”.; the most beneficial mutation is “not necessarily the one that gets fixed”; evolution does “not” look like mainstream neo-Darwinism ca. 1959.
This gives me a depressing “end of science” (John Horgan) feeling that evolutionary thinking has reached its permanent endpoint, with panglossian neo-Darwinism as the reference point for every discussion, so that whatever comes out of my mouth, the message that enters peoples’ ears is limited to “not neo-Darwinism”. It reminds me of the time I presented a very elegant constructive-neutral-evolution model of RNA pan-editing, including some precise quantitative predictions that seemed to be working out right, and an editing expert in the audience raised her hand after the talk and said “So, you’re saying its all just random?” She could have taken the model back to her lab and tested some implications, but the take-home message for her was that I didn’t agree that pan-editing is God’s special gift to trypanosomes.
What King said, and what I’m saying here, is far richer and full of implications than just saying “not deterministic”. I’m saying that the beneficial mutation that gets fixed tends to be the one favored by mutation. I’m saying that there is a conception of causation that makes sense of these effects, based on recognizing the introduction process, and distinct from the classic “forces” view. I’m saying that evolution *does* look like mutationism, with mutation providing iniative, discontinuity, creativity and direction.
Kele writes “This seems like an example of where many biologists accept these ideas but it has yet to enter the verbal conception of evolution. It is weird (but cool) how old these ideas really are. Does someone like Dawkins not agree with these ideas?”
I think “accept” is a strong word in this context, but I’m with you on “weird”.
I think I understand your frustration. Evolution not being deterministic, etc. are trivially true. A lot of the problem is that when raised under the Modern Synthesis, it is hard to think outside that paradigm.
“I’m saying that the beneficial mutation that gets fixed tends to be the one favored by mutation.”
By “beneficial” do you mean generally beneficial, but not necessarily the most beneficial? That is, in Rokyta et al., the mutations most frequently fixed are ranked 2, 3, 4 (also favored by mutation) – not 1 but not 7 or 8 either.
I apologize if I am failing to understand this specific point. This is how I understand it generally:
Not only is there a bias in the introduction of mutations (transition:tranversion rate, 4-fold degeneracy, etc.) but this bias also influences which mutations become fixed. This happens because the gene pool is not infinite – a mutation has to occur first and thus its introduction biases the proceeding direction of evolution.
Right? Not right?