So you have a model for creating catalytic antibodies. That is a start.
It is a model for random sequences producing function. I see that you will continue to avoid this evidence.
2 Likes
No, I think the evidence is great and I have seen this many times starting at bio logos.
The problem is the claims you are making with this evidence.
Now you are spewing ideology with this misleading claim. Why are you compelled to do this as a scientist?
What is the problem?
1 Like
How is it misleading?
1 Like
By dropping specifically what you have shown and using the word function alone you are claiming the mechanism can do more than you have demonstrated.
There may very well be a mechanism inside cells that causes large scale evolutionary changes. You are not going to find it by assuming you have found it at this point.
When you can model it creating new proteins that have rare functional sequences in sequence space you now are moving in the right direction.
Unfortunately once you reach this point you are still in the first inning of the game as the next step is to show how novel cells are generated.
That’s what it does.
So you’re conceding the point and doing the Gish Gallop.
Then show how it can generate prp8.
How so?
Already did that. Douglas Axe said that the chances of getting a protein fold that has beta-lactamase activity was on the order of 1x10^44. There are catalytic antibodies with beta-lactamase activity, and they were found in pool of 1x10^9 antibodies.
2 Likes
If you open your eyes you will see the evidence is that certain proteins are rare in sequence space. If you read Art Hunts paper carefully you will see this.
A new model needs to address this issue. We already have common ground that simple adaptions can be achieved through known evolutionary mechanisms.
According to Axe, beta-lactamase is one of those proteins, and the abzyme model found that protein.
Have you reconciled why the results are different as a scientist and not as a politician. I would start with the catalytic activity being high enough in Axe’s experiment to allow the e coli to survive in the penicillin solution. For this specific adaption this is the requirement. I would also consider the enzyme in Axe’s experiment is over 300 amino acids if you look at both domains.
- Growth rates are affected by the concentration of penicillin in the immediate environment. Impediments will vary from no-effect to 100% cell death in a continuum, dependent on concentration.
- The concentrations of penicillin in most environments will vary by location and result in spatial (and temporal) gradients. Thus, individual bacteria and their progeny will experience different concentrations of an antibiotic.
- Those bacteria capable of growing faster in the presence of a given concentration of an antibiotic eventually tend to predominate the immediate population. That is, increasing concentrations of antibiotics over time tends to enrich for resistance and accumulation of variants with increased resistance.
So, “survival in a penicillin concentration of ‘x’ mM” is not a great proxy for the initial evolvability of an enzyme’s catalytic activity. If direct enzyme assays were difficult, I’d probably use chemostat-like methods of continuous culture with sub-lethal levels of an antibiotic. That method tends to identify small variations in activity pretty well.
3 Likes
I would suggest you take your own advice.
1 Like
If you are right what we are observing in Axe’s experiment is a bacteria that contains an enzyme that has a 300 plus aa sequence that has a high enough catalytic level to survive a high concentration of the antibiotic.
That’s obnoxious. Why should I do anything for you when you’re too proud to admit when you are wrong?
How can you have been trained in applied math when you’re clearly afraid to apply math to evolution?
Why do you think Axe didn’t bother with doing any quantitative enzyme assays?
They’re not:
There’s the possibility that Axe did some assays but didn’t like the results…
Yes. If I had been a reviewer of the paper, I would have rejected it because Axe didn’t do any beta-lactamase assays. That would be my response regardless of the results.
Have YOU reconciled the results mathematically? Show your work.
What is that in units, Bill? Why didn’t Axe do any assays?
So what? The V regions of antibodies are 110 residues each x 2. That’s irrelevant mathematically, but I think you know that.
Also, in a protein they are no longer amino acids. They are amino-acid residues. The acidic part is gone.
It’s better than a model, it’s an observation. An observation you think should be impossible.