Gpuccio is estimating how much function is out there by seeing how constrained the sequences are in its present function. This creates a vehicle to make an estimate of how much functional space there is. This is an empirically based calculation. What you don’t have is evidence of other function or paths to really challenge his argument. They could be there is not a strong case.
The problem is that measuring the window of evolvability tells you absolutely nothing about the size of the target space. This point has been made over and over.
All it tells you is that there is a paucity of viable sequences in the immediate vicinity of sequence space, which gives no insights into what sequences might exist in more distant sequence space.
True. The preservation data does.
And how does that show there are no other sequences out there that can perform the function?
This creates a vehicle to make an estimate of how much functional space there is.
How does it do that? How does the constraint operating on one part of sequence space, tell you about another part of sequence space further away?
What you don’t have is evidence of other function or paths to really challenge his argument.
It’s not my job to know, it’s yours. You are the one claiming to know the number to plug into the calculation, so you have to justify your implicit claim that there are no other such sequences.
They could be there is not a strong case.
How do you know?
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It doesn’t. It shows there is a limit to functional space.
What other functional sequence space further away? How did evolution find this very restrictive space 400 million years ago and not move if more than 50% of the sequences are substitutable in every location?
Because you are making an argument from speculation.
No, it doesn’t. The preservation tells you about the window of evolvability, nothing more.
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You’re claiming that it evolved into an un evolvable state?
Then how do you justify the number you plug in to the equation?
It shows there is a limit to functional space.
That isn’t in question. Nobody claims all of sequence space can perform the function of some given protein.
Well if only 10^12 sequences are know to have been tested in real organisms, how can you claim there is no function in the remaining part of sequence space?
How did evolution find this very restrictive space 400 million years ago and not move if more than 50% of the sequences are substitutable in every location?
One possibility is that it was already nearby in sequence space.
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He’s saying it crawled to the top of the hill. When you’re up there, all directions lead back down.
That’s entirely possible, you should be familiar with the evolutionary explanations for so-called irreducible complex complexes by now. Add a part, make it essential. Once that part is “locked-in”, it’s ability to change can be severely hampered.
The protein could have evolved by a particular route through sequence space, and there’s no guarantee it’s free to go back the same way without affecting its now-essential function.
To what end? Just curious.
It is the best estimate we can make at this point. I believe the evolutionists assumption that many other sequences can do the job is false because of the interdependence of cellular processes. If I am right then the calculation is quite accurate. What we are observing is a designed sequence where its function is highly dependent of a very precise sequence.
The case that it evolved into that state is very challenging as the preservation show some limit of substitutability. Even with 50% substitutability of the AA’s in prp8 there is 2335 bits of FI.
We are at a stand off here and playing burden tennis.
This is a claim of serendipity?
But that’s you doing the speculation here. When you claim to know the FI for some protein, you are claiming to know the number of sequences that meet M(E_x).
When you do that, you are claiming to know that sequences you haven’t tested don’t meet it. Sequences you haven’t tested. So you are speculating.
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I am claiming the preservation data is a valid test for estimating function in sequence space. The fact we are observing AA sequences that are not moving despite DNA mutation is significant.
But how does the degree to which a protein is conserved tell you about other sequences far away?
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If you break PRP8 down into its functional modules (after all, didn’t someone say function somewhere in this conversation?), the value for FI falls off a cliff.
As does the proposition of its vast, immutability irreducible complexity and improbability.
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No. What you are claiming in this statement is, basically, that 1 (the value used by @gpuccio et al. when they use BLAST to deduce the numbers of functional sequences) = 10^100 or more.
That’s some mighty funny ID/cretaionist math there.
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This appears to be true but what is the point? Function here is ultimately defined by splicing as prp8 is only a piece of a much larger function. The evidence is that only a very select sequenced of AA’s will allow this precisely enough for the organism to survive.
No I am claiming exactly what I am claiming. Why the straw man?
No, not survive. We don’t know which mutations cause lethality as opposed to just lower fitness. And in any case, we are only dealing mutant versions of a set of similar sequences. We stil don’t know about the possible functions of entirely different sequences.
The fact that we have not detected an organism with a particular amino acid in a specific position of it’s Prp8 homologue does not mean a protein with that amino acid would be lethal. It could just be deleterious instead.
On a related note, we also have to consider that the variation we see is in part an artifact of our sampling. We know there are still many species out there we haven’t sequenced yet. When you calculate FI with a historically contingent estimate for the number of sequences that meet the minimum threshold for function, you are essentially claiming to know that there are no novel variants out there with amino acids we haven’t yet seen.
One could go on and on about things you can’t claim to know and yet you do so anyway.
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