Thanks for the correction and discussion. I think your argument regarding catalytic antibodies is quite interesting. Axe’s experiment is what it is and a small piece of the overall evidence.
That would always depend on the penicillin concentration. There is always some threshold below which any organism can strictly survive exposure to a novel antibiotic it has not previously been exposed to.
That’s one of the ways organisms evolve resistance in the first place: They survive in the boundary zones where the concentrations are low, and keep reproducing until fitness increasing mutations that allow survival in higher concentrations occur.
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Can you model this? How do get to a sequence space that is 10^-77 for a tested function from a low level of catalytic activity given you need to make a blind search through a sequence. You need enough selectable steps along the way but even the low level catalytic activity has a functional sequence space of 10^-8 or -9.
I seems much more likely that random change will move you away from function.
It’s been observed.
You have seen it go from one state to the other?
if its so easy to evolve new proteins, why we cant test in the lab how a protein like globin can evolve from non-globin?
@scd, this sounds like the old fallacy based upon the well-worn misunderstanding of “repeat-ability in science.” I remember it from my “creation science” years in the 1960’s and 1970’s.
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Sorry for not being clear. What I meant is that of b-lactamase activity might be below the limits of detection for some assays.So activity can be difficult to detect by direct assay yet still have a noticeable effect in vivo.
Yes. One can use point sources of antibiotics.
The 10^-77 is not consistent with the vast majority of the evidence. It comes from a backwards experiment that did not assay enzymatic activity, so calling it a “tested function” is bogus.
Since you’re such a fan of Axe, please answer the following questions:
- Is starting with a thermally unstable, ts mutant a good model for evolution?
- Is going backwards from a crippled protein a good model for forward evolution?
- Is changing 10 residues at a time a good model for evolution?
- How many other studies have been published that are relevant to the frequency of function in sequence space?
If you can’t answer these questions with convincing reasons, you have no business touting Axe’s 10^-77 as a reference value.
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The bottom line is that Axe couldn’t be bothered–or maybe he did the assays and didn’t like the results. They are easy to do.
The catalytic antibody space in which they found b-lactamase activity was in the territory of 10^-9 to 10^-12, I think.
Better than that. More than one in 10^8.
As I said before it’s a single data point. You have made another data point. Saying Axe did not generate useful data is inaccurate in my opinion. I agree with you that he did not create a model for evolution.
He was experimenting with a real functional enzyme and tested its sequence flexibility in a laboratory e coli environment. This is my opinion I understand your position that you think it is invalid. I will continue to read your arguments.
So Axe has demonstrated that it is possible to intelligently design an experiment that is sure to fail to produce a particular result that he didn’t want to occur. Well, isn’t that just great for him.
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It turns out that sequence is much more flexible than his model predicted. Therefore, his model is wrong.
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actually axe mention several of them, with similar result, up to 10^60 for 100 aa long proteins.
It’s not even a data point, since you haven’t explained why 1) going backwards, 2) starting with a mutant selected on the basis of instability, and 3) mutating 10 residues at once are relevant to evolution.
False. I’ve pointed you to THOUSANDS of data points that Axe ignores.
Your description of thousands of papers as a single data point appears not to have been made in good faith.
Your opinion is based on ignoring the evidence. For what is his data useful?
Not a wild-type enzyme, a deliberately DYSfunctional enzyme that wilts at physiological temperature. Why did he start with a ts mutant, Bill? As someone who has studied mutants for decades, the answer is obvious to me.
But you won’t look at the evidence. That says it all.
And he didn’t mention many others. Was that ethical behavior?
That explains why there were no enzymatic assays included.
It’s a method of estimating substitutability at each position. He used an unstable position as he needed to see the points of failure. If he used the wild type he would unlikely see failure with his substitutions.
Whats relevant to evolution is how many AA’s can do the job at each location.