So how do you propose prp8 evolved? Where did all these preserved sequences come from? All this random activity of non related sequences and poof you get one of the pieces of a splicing machine?
As is so often the case, PRP8 probably comes from a retrotransposon.
How did the retrotransposon sequence evolve so that it was compatible with prp8 function?
If you’re honestly interested in learning what is known about your question, why not read the paper (and perhaps subsequent papers that cite it)?
I had already read it. While an enzyme that can write RNA into the genome may have similar characteristics to a central unit of the spliceosome it is not clear at all how one becomes the other or combines with other segments.
I have ready papers like this over the years and they never ask the question did X evolve. They never explore the extreme challenges involved in the claim. They assume it evolved, find something common somewhere else and then declare this is how it evolved.
We are observing 4 sequences of 1000 to 2000 AA’s that are almost perfectly preserved over 50 million years and the claim is that these came from other borrowed sequences?
If the answer is no then your appeal to the Prp8 protein as some sort of evidence for you claim that knowing the size of sequence space tells us something about how frequently we find function, or overlapping functions in that space, makes even less sense than it already did. Which is remarkable since it already made zero sense.
Why did it already make zero sense? Because even if the currently known Prp8 protein sequences are the only proteins in ~2000 amino acid-long protein sequence space capable of carrying out the Prp8 function, that says nothing about whether there are other potential functions in that space, or how many of them there are, or where they are in relation to Prp8 sequences.
Literally NOTHING you’ve said so far makes any sense.
You conclude that on the basis of aligning a human, a mouse, and a rat sequence, and you now feel like you’ve substantively sampled mammal diversity?
What does that even mean?
We already know you believe this. What we are missing are arguments that entail or imply this conclusion from the known facts. No argument so far given by you have done anything to move you closer to that conclusion.
You may feel like you’re somehow answering us here just because you’re able to type words into your browser window and click the “reply” button, but I’d just like to point out here that you’re still at a score of 0. Nothing. Nothing you’ve said have rendered your conclusion any more plausible or even sensible than when we began this argument. You have yet to say something that gets your argument to a place where it even makes sense.
For fucks sake Bill, that is just your conclusion re-stated. Why not conserved because variants selected against are significantly deleterious in comparison? Please don’t just repeat the claim again in other words.
Why would you expect more variation over millions of years if that variation is strongly deleterious instead of lethal?
That is pathologically dichotomous thinking. The point is, slower or occasionally inaccurate splicing is not the same thing as no splicing at all. You understand the concept of gradations right?
How? How does the level of conservation establish that?
How do you know that?
That’s the conclusion of your argument again, it’s not supporting reasoning. The high levels of conservation does not deductively entail lethality of change. To get to that conclusion, you need more premises in your argument. You need something else which combined with conservation would entail that. I’d like you to explain what that is.
Of course I’m not really so delusional I really think you have any other premises, that much is clear by now. You just flat out perform a textbook nonsequitur. I don’t understand why it’s not obvious to you that your conclusion is neither entailed nor implied merely from the degree of
conservation.
That makes no sense at all. How would “the application such as splicing” allow us to determine if a hill exists?
That’s not an argument, that’s a claim.
The data in gpuccio’s graph does not support this and the gap is a 1000 orders of magnitude in some cases.
Gpuccio’s graph still doesn’t make any sense to me. It’s gobbledygook, but it’s a graph constructed with pro-ID intent, so it has the veneer of scientific technically, and that’s all it takes to get you on board. It doesn’t have to make sense, it’s pro-ID and sorta kinda looks like science, you’re in!
Complete pseudoscientific bullshit believed with an irrational level of conviction seemingly out of nothing but sheer confirmation bias.
Thats because you committed to it not making sense. You are not looking at the data with the possibility you might be wrong. The data is telling you that rarity of sequences scales with sequence length. This is what the data is telling you. Like origin of life you default to appealing to speculation based on your pre conceived notion.
This is not the purpose. What are the odds of having those sequences in both almost identical if they were mutating. Why are they not mutating? The specific sequence is is critical to the splicing function. In all four cases.
You can always make a speculation. Until you embrace the evidence you can always convince yourself that it is something else. As long as you feel top down that evolution is a fact no amount of evidence will convince you. Again, as you are doing here and you did with origin of life your default is to speculation when the facts don’t favor your position.
Yes and criticism of evolutionary speculations is labeled pseudoscience. This alone shows how much trouble the theory is in. This is not very convincing to an objective viewer who understands the political tactic of labeling.
What data? Gpuccio’s crappy graph? No, that doesn’t show that. You can’t derive a trend about protein evolution in general from a sample size of three. There are tens of millions of different proteins. You OBVIOUSLY can’t make a claim that some trend obtains about their properties and relationship to sequence space from three different proteins.
This is what the data is telling you.
No, it’s just what you believe.
Like origin of life you default to appealing to speculation based on your pre conceived notion.
I have offered no speculations of relevance to this discussion of the claims you’ve made. You just seem terminally incapable of valid reasoning.
Then whatever the hell your point was by referring to the mouse, human, and rat sequences now makes even less sense. Which is a remarkable achievement in itself, since it already made very little sense.
What are the odds of having those sequences in both almost identical if they were mutating.
That depends on how strongly variation was selected against?
Why are they not mutating?
You mean why didn’t the mutants get fixed in the population? Well here we both agree, they were selected against. Now the question is why were they selected against, is it because the mutants were completely nonfunctional, or because they had substantially lower relative fitness?
The specific sequence is is critical to the splicing function. In all four cases .
Sure, but so what? That doesn’t tell us whether potential mutants were selected against because they had lower fitness, or because they were completely nonfunctional.
I invite you to see that this is what you’re doing. You are believing your own speculations on no evidence at all. And you seem unable to work out that the data you refer to isn’t evidence for your speculations, for reasons I’ve been trying to get you to understand.
As long as you feel top down that evolution is a fact no amount of evidence will convince you.
I don’t know what it means to feel something “top down”, but I suspect that’s actually what you’re doing and projecting it on to me instead. Which explains why you don’t even seem able to do reason properly. Forget about what the evidence actually says, you don’t seem to understand what evidence even is.
Again, as you are doing here and you did with origin of life your default is to speculation when the facts don’t favor your position.
I have offered no speculations as arguments anywhere here except to show that there are options you have been unable to logically rule out.
You argue from certain facts as if they logically entail a particular conclusion. I point out that there are other potential conclusions which are compatible with the same set of facts, and then something weird happens because you don’t seem to be able to get that into your brain and make it settle, you just regurgitate your conclusion again without being able to explain how you rule out other compatible conclusions. That’s what I’ve been trying to get you to understand all along.
You take some fact (there is some X amount of conservation in some set of sequences), and then you perform either something like an invalid deduction, or an extremely poorly supported induction(like drawing a trend from a sample size of three).
You jump straight to the conclusion that no other variation is possible. I try to get you to consider that other conclusions are actually compatible with that same set of facts, and I do that by trying to get you to explain how you rule those other conclusion out. This is where you just repeat your conclusion, or draw on another fact that ALSO doesn’t entail your conclusion, or make a hasty generalization based on extremely limited samples.
Bill, please, please, please for you own goddamn sake, try to actually allow yourself to think.
No, mere criticisms of evolution aren’t labeled pseudoscience. Attempts to produce evidence for ID based on flawed methodology that has the superficial appearances of being science, by employing technical-sounding jargon, is labeled pseudoscience.
This alone shows how much trouble the theory is in. This is not very convincing to an objective viewer who understands the political tactic of labeling.
An objective viewer? Don’t make me laugh.
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Make a case with more proteins that proteins preservation are not scaling with sequence length.
Sure because it makes sense and I have not seen the data contradict this idea yet.
Why did you quote mine here?
If it was fitness don’t you think there would be more variation?
Rum I am the only one providing data so far except Dave’s paper. Its your turn if you can piece together a data supported argument how evolutionary mechanisms can find these sequences that have not mutated over 50 million years.
You have 4 cases of 1000-2000 AA proteins in the same complex that have not mutated over 50 million years and your claim is that known evolutionary mechanisms created these sequences?
Dunno. But the point is that nothing you have said so far has anything to do with how hard it would be to find that hill, and thus nothing to do with how hard it would be to evolve those proteins.
No, it found a peak. You don’t know there’s only one peak, and nothing you have done or shown addresses the question of how many peaks there are.
You understand all eukaryotes are apparently standing on the same peak, which was reached once, before the common ancestor of all eukaryotes. Right?
Don’t know. Why?
No, YOU make that case. It’s YOUR claim. It’s not automatically true until I prove it wrong with more data. It’s automatically disbelieved until a volume of data sufficient to warrant belief is provided. That’s the only rationally defensible position to take. You refrain from accepting a claim until it has met a rational burden of proof and not a second before.
No, the data isn’t telling you that. You don’t have enough data to support that conclusion, so it’s not telling you that. That data is compatible with literally billions of other models. A sample size of three is statistically insignificant here. You can make no rational claims about what the data says based on a comparison of three proteins. It’s absurd.
And the point is you don’t understand that the data you are providing simply isnt’ enough to substantiate your conclusion. What you’ve copy-pasted from Gpuccio is of no value or consequence.
Its your turn if you can piece together a data supported argument how evolutionary mechanisms can find these sequences that have not mutated over 50 million years.
No, it’s not my turn to do anything at all except point out your seemingly endless errors in reasoning.
Simply looking up the Prp8 protein on wikipedia will tell you there are human Prp8 mutants living among us, and some of these apparently negatively affect vision, leading some of them eventually go blind in adulthood. That’s strongly deleterious, which would explain why such mutants haven’t fixed in the population. But they’re clearly not lethal, since there are people running around with them.
One could probably go look up other variants of it in the human population. Now your claim is we should find none, because there is no hill, and it’s so conserved it means the majority of variants are lethal.
and your claim is that known evolutionary mechanisms created these sequences?
I don’t need to make any claims about how Prp8 came to exist. You will never get out of having to support your burden of proof. That’s just how it works.
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This all is irrelevant to the fact that we have shown that the application is sequence sensitive. Peaks or multiple peaks are your speculation. I honestly don’t see you or Rum changing your mind no matter how compelling the data is.
You have no empirically supported evolutionary explanation for how we could get in a state where the animals splicing sequences are not mutating over long periods of time.
This theory (Universal common descent by known evolutionary mechanisms) is in about the same shape as origin of life research.
Three proteins and you are compelled. LOL
“We”? You haven’t shown anything. I have no idea what “the application is sequence sensitive” even means.
Sproing!
Well of course they mutate. But mutations are selected against. After all this time, don’t you know the difference between mutation and fixation? And, apparently, between splice signals and proteins?
You only think so because you have no understanding of either.
I just ran prp8 alignment against Guinea Pig Rabbit and Humans. 100% alignment. 2335 amino acids. How did all three get to the point where there are no fixed mutations over millions of years? Whats your explanation?
How did they mutate to exactly the same AA sequence? Why did not even one mutation get fixed in the population by selection or drift?
The answer is likely that splicing requires precise AA arrangements in mammals.
They’re sitting on an adaptive peak. Note that the peak seems to shift slowly, but it does shift.
This is hopeless. They didn’t. They all have the sequence of their common ancestor. Inheritance, not convergence.
Apparently the peak is very small.
Word salad again. “AA arrangements”? The answer is that, given the environmental conditions and other molecules with which it must interact, all changes in the prp8 protein sequence are deleterious in, apparently, Euarchontoglires. (Possibly in other mammals too, though you have not shown that.) Note that “deleterious” doesn’t mean “fatal”. Fairly small negative selection coefficients can prevent fixation.
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I would like to summarize, for my own benefit and perhaps for others, this Prp8 discussion:
According to Wikipedia: “The Prp8 protein is a large, highly conserved, and unique protein that resides in the catalytic core of the spliceosome and has been found to have a central role in molecular rearrangements that occur there.”
The question seems to be two-fold:
- how did the Prp8 gene originate given its large size and importance to generating translatable mRNA? Is this an example of an irreducibly complex biochemical system?
- why is Prp8 so well conserved (61% identity match between humans and yeast according to Wikipedia, and 100% for Guinea Pig, Rabbit, and Humans according to @colewd) ?
So on the ID side (@colewd) , the argument seems to be:
- with a 2,000+ amino acid sequence, the odds of this particular sequence just showing up are astronomically low. Additionally, since Prp8 plays a critical catalytic role in splicing, the allowable number of amino acid sequences that would retain functionality is probably pretty low. To use the terms “sequence space” (possible amino acid sequences) and “function space” (amino acid sequences that provide a particular function) – the function space is very small and the sequence space is very large. I would call this not being robust to mutation but I’m sure the biologist have a term for it.
- Prp8 is so well conserved precisely because it is “fine-tuned”, in a sense, for the job.
On the non-ID side (@John_Harshman and @Rumraket primarily), the argument seems to be:
- We don’t know what other similar proteins could have served a similar, though maybe not as efficient, role as Prp8 in the past, but it’s easily conceivable that the particular amino acid sequence we have now is not the only one that would do the job well enough to support splicing activity. The “sequence space” does not have to have always been as large as it is now and the “function space” could be much broader if inefficient sequences are considered. The ID folks are being too picky by only focusing on the Prp8 gene that resulted from the evolutionary process.
- Prp8 is well conserved because there is selective pressure to retain the amino acid sequence we have. Mutations occur of course, but negative selection prevents most mutations from being fixed – the amino acid sequence we currently have seems to be (at least locally) optimized.
So, a couple questions:
- Is this a decent summary?
- how could we experimentally determine how “robust” Prp8 would be to mutations?
- how could we experimentally determine how optimized the sequence is towards function?
These last two questions are related but separate, I think.
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We could try all possible combinations of mutations and test them for activity. Good luck on that. Of course I would presume that many spots in Prp8 are coadapted to interact with the sequences of other proteins in the complex, so one might need to consider the space of all possible complexes rather than just one peptide. Even better luck with that.
But what would you learn? You would learn what sequences would have some function of Prp8 in the current environment. This is a far cry from learning what sequences would have had function in the ancestral environment, which may have included fewer or quite different proteins in the complex, a much smaller Prp8, and other differences from the modern system.
Not sure what the question is. “How optimized” on what scale? It’s optimized enough that departures are highly likely to lower fitness; that is it must be sitting on a local peak, so as far as its immediate neighbors in protein space, it’s optimal. Whether there are other, perhaps higher peaks elsewhere in protein space is even harder to test.