That’s just laughably false. Specificity does not correlate with stability. Nor does functionality.
This idea that Axe and Miller are trying to sell, that stability is some sort of proxy for function, is absurd in the real world.
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So far I as know, only the ACE2 receptor and TMPRSS2 is involved in SARS-CoV-2 cell entry. Are there others?
What other human receptor than ACE2 do you have evidence Omicron spike interacts with, to a greater extend than previous variants? Sounds to me like you’re making things up here.
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Mostly dead implies slightly alive, and that there’s something that can be done besides going through it’s genome looking for random change.
I got one reply on reddit(don’t mind the ant-vax guy, that’s how he usually is). How would you respond to it?
Rumraket hits on this several comments down, saying Brian Miller “appears to not understand that purifying selection can maintain structural stability of a protein against destabilizing mutations.”
Yes, that is clearly implied by Miller trying to argue against a case of a protein evolving from being able to perform one function, into another similar protein that carries out a different function. He’s being quite clear this is what he is trying to accomplish with this argument. He’s not just trying to argue that to discover a new functional protein de novo is very unlikely, he’s also trying to argue against the idea that, for example the flagellum’s filament protein - flagellin - could have evolved from another protein that was less than 90% similar to it.
By Miller using research on protein stability, where mutations were allowed to accumulate without selection to see how many it would take on average before the protein destabilized, to argue against proteins being able to accumulate mutations over time, he really does appear not to understand the rule of purifying selection in these sorts of random walks in protein sequence space.
Yes, when selection is not included, then after relatively few mutations the protein is pretty much guaranteed to destabilize. Hence mutations without selection can’t just accumulate willy-nilly and indefinitely, and you would, without selection, expect the protein to become nonfunctional long before a new function was found (supposing, just for the sake of argument, that 10% of the sequence has to change to find a new function).
The whole point here is that the very same research indicates that when purifying selection is included, the protein really can continue to accumulate mutations well beyond those 5-10 amino acid substitutions, or 10% of sequence length, or whatever “limit” Brian Miller thinks there is. I make this same point in this post.
But why does Rumraket think Miller is talking about a case of purifying selection? In Rumraket’s second source, Miller even says he’s talking about a case of weak selection: “After only a few random mutations (1-2) under weak selection , around a third of subsequent changes to a protein completely disable it.”
This fellow is confused. I am not arguing that the strength of selection changes the proportion of mutations that are destabilizing versus stabilizing. I am arguing that Miller is ignoring selection when he argues against the long-term accumulation of mutations in protein sequences. When Miller is trying to cast doubt on the possibility that, for example, the flagellum’s filament protein flagellin could have evolved incrementally from another protein that is less than 90% similar, by appealing to research done trying to establish how many mutations it takes, on average, to destabilize a protein.
That research shows it takes only a few without selection (because on average more mutations are destabilizing than stabilizing), but when selection is included, the protein actually doesn’t destabilize because now the destabilizing mutations are either selected against(those mutants have lower fitness because their protein falls apart more often), or being compensated for by the fixation of stabilizing mutations.
This is an absurd misunderstanding of the waiting time problem. The waiting time problem refers to when you need two simultaneous, specific mutations before a fitness gain is realized.
No, it just refers to two(or more) specific mutations. The whole problem with the waiting time argument (I’m now explaining what is wrong with the waiting time problem-argument) is that it asks us to pick out particular combinations of mutations (two or more) and then asks us to calculate the odds that that specific “target” set of mutations would occur. And since it would take a lot longer to wait for two specific mutations, rather than to wait for just any two mutations, any time we find that two sequences are different from each other by some number of mutations we could argue they couldn’t possibly have evolved from each other (or from a common ancestor) in the available time because our calculation shows it would take an inordinate amount of time before that set specific set of differences to have occurred. I have a post that explains the problem with the waiting time-type of arguments here:
No reason to go over the rest of this fellow’s post because he doesn’t seem to know what I’m referring to. Yes, creationists (such as John Sanford) really have argued that to get some specific set of mutations takes a really long time on average, and therefore evolution is false because we find that two things A and B have that many differences, and that is regardless of whether those mutations each confer a selective advantage or not.
And he’s actually right. The math generally checks out. It really would take a really long time to wait for that specific set of 2 or more mutations. It’s just that those aren’t the only possible set there was, it was just the one that occurred.
It doesn’t apply when:
- The mutations can happen one at a time with a gain in fitness at each step.
Flat out wrong. It still applies. The math still shows that if you need to wait for two specific mutations, even if each of them carries a fitness benefit, it will take a loooong time for those two specific mutations. And if you pick out three specific mutations, it gets even worse. And so on and so forth. The whole argument here is about specific target sequences vs any sequence that works.
If anyone thinks this is all just “creationist nonesense,” here’s Larry Moran saying the same thing:
- “The probability of any single mutation occurring is equal to the mutation rare, which is about 10-10. The probability of an additional specific mutation occurring is also 10-10. The combined probability of any two specific mutations occurring is 10-20… Let’s say that three specific mutations are required to change from a cluster of two needles to a cluster of five needles. One hundred million years ago you could calculate that the probability of three specific mutations is about 10-30. It’s highly improbable, just like the specific bridge hand. When such a triple mutation arises we recognize that it was only one of millions and millions of possible evolutionary outcomes.”
Uhm, yes, exactly. That’s my whole goddamned point. That it makes no sense to pick out specific sets of mutations after the fact and declare them to be a “target sequence” that couldn’t possibly evolve because it would take too long(nor does it make sense to calculate the mean time to establishment of some X number, as that treats them as a target too), exactly because it is just one possible set that evolved out of many others that could. It was never a “target” to begin with. It’s just a contingent outcome of history.
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Hi Rum
How does this apply to the theory that proteins evolve from pseudo genes or NC DNA?
I wonder why that guy stopped reading at that point of Moran’s article? It’s too bad. He would have learned something.
The flaw in Behe’s argument is that he assumes that the tape of life will always play the same movie. In other words, every organism we see today must be the product of an extraordinary set of mutations and fixations that had to play out just the way they did. For example, let’s say that the difference in needle clusters between red pine and white pine are determined by a single gene. Let’s say that three specific mutations are required to change from a cluster of two needles to a cluster of five needles. One hundred million years ago you could calculate that the probability of three specific mutations is about 10-30. It’s highly improbable, just like the specific bridge hand.
When such a triple mutation arises we recognize that it was only one of millions and millions of possible evolutionary outcomes. There was no a priori requirement that Earth contain red pines and white pines just as there’s no a priori requirement that you get a specific hand in the next deal.
This is hard for IDiots to understand since they begin with the assumption that humans are the designed outcome of the history of life on Earth and they assume that evolutionary theory has to explain why the tape of life will always play out in the same manner every time.
They can’t conceive of an alternative history that didn’t have Homo sapiens or white pine trees. If they are right, then Behe’s argument makes sense. Evolution can’t do that. But all the evidence we have indicates that they are wrong, and Gould is right1. Behe’s argument makes no sense in the light of evidence of evolution.
There is an edge of evolution and it rules out design in favor of accident and contingency.
Hopefully he will join us here on the forum and we can help straighten out his thinking.
BTW, I loved his attempt to explain purifying selection:
Imagine you have 100 vials of liquids, everything from water to lemonade to bleach to mercury. After giving the vials to 1000 people you find that a person will die after drinking 3 vials.
Then you repeat this experiment on many generations of people. As expected, 1/3rd of people die each generation. But the whole population won’t go extinct after 3 generations–in fact it will go on forever. This illustrates purifying selection.
No, sweetheart. That’s not how this works at all…
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LOL I just skipped right over that but oh boy that is one catastrophically bad analogy.
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Just a small correction (maybe I am mistaken?). They would say that, if each mutation has a benefit, then you can have the following scenario.
Population = 100% wild type
Population = ~100% wild type + 1 beneficial mutation
Population = 100% mutant 1 (due to selection)
Population = ~100% mutant 1 + double mutant more beneficial
Population = 100% double mutant (due to selection)
Which is more likely to happen then the scenario they propose if 1 mutation is not beneficial:
Population = 100% wild type
Population = ~100% wild type + 1 double mutant
Population = 100% double mutant (due to selection)
Although I would say that the previous scenario can also happen even if both mutations are needed for a beneficial effect, simply due to drift. E.g.
Population = 100% wild type
Population = ~100% wild type + 1 potentiating mutant
Population = 100% mutant 1 (due to drift)
Population = ~100% mutant 1 + double mutant more beneficial
Population = 100% double mutant (due to selection)
[Of course, the second mutation can happen before the previous mutations reaches 100% frequency. Just simplifying it here]
It doesn’t. Junk-DNA just accumulates mutations until some adaptive function is found, at which point the function being adaptive necessitates it being under selection, so that stabilizing mutations that positively affect fitness get selected for and destabilizing ones get selected against.
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Of course having each individual mutation being beneficial does speed things up (it speeds up the time to fixation, it doesn’t speed up the probability of occurrence, you still have to wait for the mutation to occur).
But it is still the case that, with a large enough set of specific mutations, the wait becomes incredibly long before all of them have accumulated. Obviously factors like mutation rate, genetic recombination, and population size also make a difference too, besides just the fitness effects of mutations.
But it’s trivial to show that with a sufficiently unlikely “target” set of mutations (even if all of them are beneficial and population size+mutation rates are high but realistic), the wait becomes absurd. The most significant problem with waiting time-type arguments is the target thinking.
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Actually it does. Just to simplify, let’s say the odds of the beneficial mutation(s) is 1% (per generation or time, doesn’t matter in this case), and the population size is 100. The odds of 1 beneficial mutant appearing in the population is 1-(99/100)^100= ~ 64%. Then after this mutation is fixed in the population (again 100 individual), the second mutation also has the probability of ~64%. Total probability is ~0.64^2= 42.25% [Obviously ignoring the effect of drift on the probability of the first mutation reaching fixation]
Now, regarding the scenario (according to the ID-folk, which I do not agree with) that is required for when you need 2 beneficial mutation together to have a beneficial effect, you need to have the mutations occur in the same individual at the same time, i.e. 1/100^2= 0.01%. Within a population of again 100, that is 1-(99.99/100)^100= ~1%.
The difference is that in the previous scenario the mutations can occur in different individuals, (although one being an ancestor and one a descendant), while the second requires the mutation to occur in the same individual. The difference between 1 person winning the lottery + in distant future (when everyone alive is a descendant of the winner) again 1 person winning the lottery - and - 1 person winning 2 lotteries at the same time.
I agree that all of this is trivial. As I said previously, these mutations don’t have to occur at the same time. One can be driven to fixation (or at least to a relatively high frequency) by drift before the second mutation, and (as you mentioned) this is target thinking. There were and are likely countless potential unique beneficial (combo) mutations that were never realized. The ones that played the lottery, but they never won or will win the game.
I had to read that part a few times before realizing it was bs.
BTW, you’ll love his website where he lays down his arguments against evolution. The main one is his argument that evolution is too slow to produce all the “information” we see in organisms today because the amount of mutations accumulated in viral populations of similar size today is too low compared to the amount of “functional nucleotides” that needs to be generated since the last common ancestor of mammals(the amount he calculates in 170 billion). Here is how he gets that number. He’s also debated this multiple times with dsternecardinale.
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Brian Miller, #2004 The Encyclopedia of American Loons. “…we have found no real research record and hence no indication that Miller is actually a scientist in any legitimate sense of the word.” Diagnosis: Pseudoscientist, denialist, fundamentalist, and conspiracy theorist. One of many, but unlike most Miller could, given his legitimate credentials, be confused for someone with something worthwhile to say (and the DiscoTute apparently wants to make damn sure that such confusions happen). He isn’t. Move on.
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