So, if I understand you well, you think that for a given complex function, there are many local optima, ie., many alternative solutions, in the sequence space. Let’s take the example of the beta chain of ATP synthase. This protein has 529 AAs, exhibits 334 identities between E. Coli and humans, and, according to gpuccio’s methodology, this translates to an FI of 1297 bits. You contest gpuccio’s calculation of FI because he only considers one functional island for the protein whereas you think there are many. But the question here is how many?
Do you realize that in order to reduce the FI of the beta chain of ATP synthase from 1297 bits to below 500 bits, you have to postulate that there are at least 10^240 alternative solutions in the sequence space that can implement the same complex function! Given that there is no evidence whatsoever that other alternative solutions exist for the beta chain of ATP synthase, I would say that to believe there exists 10^240 amounts to believe in Santa Claus.
Do you realize no one has ever shown natural evolutionary processes can’t produce or increase what you call “FI” so your numbers are meaningless?
Okay, I see you still believe in Santa Claus😉It’s your right after all.
I can do math.
Exactly.
“FI” doesn’t measure sequence conservation. It doesn’t measure functional sequence space. It doesn’t measure total sequence space.
It’s a fantasy.
That’s a silly attempt to shift the evidentiary burden.
The point is that “FI” doesn’t detect other optima. The point is that YOU don’t know, yet you claim to.
There may be many functional alternative solutions, but that doesn’t make them all local optima. It actually appears that for ATP synthase no such inescapable “local optimum” has been found, as the sequences of basically all it’s subunits have been diverging for all cellular organisms, continuously for the entire known history of life.
No, that isnt’t the reason I am contesting his calculation. I am contesting his calculation because the method isn’t capable of determining how many functional sequences there are.
It’s not merely that I think he’s wrong that makes me contest his calculation. I am contesting the calculation primarily because:
- The method is based on a sampling process that has extremely high intrinsic bias.
- The fraction of sequence space the process samples is an infinitesimally small one.
His method is not capable of telling us how many functional sequences there are. For reasons explained now so many times it boggles the mind anyone would have still have trouble understanding it.
As stated before, even if Gpuccio’s number is actually correct(which there is no good reason to think), the method he uses is not how that is established, and he would only happen to be coincidentally correct in the number. Sort of like if he had happened to correctly guess the true number of functional sequences, and it was later found to be corroborated in some elaborate experiment, that would not mean that just guessing is how we determine the FI for some protein sequence. No, we really do have to use a method that is capable of telling us that, and for reasons given above many times, sequence conservation used to derive FI isn’t how that is done.
Functional sequences, not just local optima. But yes, how many functional sequences are there? You can’t extract that information from picking extant sequences from living organisms and extrapolating from that.
So an invisible, telepathic, palestinian Columbidae, from classical antiquity, instead of Santa, must have made it?
In all seriousness, you seem to have this weird picture in mind where there was a not-yet-fully-formed ATP synthase molecular machine, that lacked subunit beta of the F1 hexamer, and evolution had to sort of “find” a functional beta-subunit before the system would function. It’s the Hoyle-fallacy all over again.
But of course that’s not how these things happen. The individual proteins that make up ATP synthase have ancestries that go back to times before they became part of the ATP synthase complex. The real question is how frequent is the ultimate ancestral function of the entire superfamily to which the beta subunit belongs?
The beta subunit did not evolve de novo into the ATP synthase complex, rather it belongs to a gigantic superfamily of proteins called P-Loop NTPases(which, ironically, also contains the actin and myosin subfamilies), one of the most divergent and oldest protein superfamilies known. The beta subunit is part of the catalytic hexamer(the one that also contains the Walker-A motif), which is actually functional on it’s own as a DNA and RNA translocase(and as an RNA helicase).
The most basic function of all P-loop NTPase members is nucleotide binding (and hydrolysis). That is the inferred ancestral function and the essential role of them all.
That’s the function they tested for in the Keefe & Szostak 2001 experiment (ATP binding), and found to exist at a frequency of approximately 10^-11(noteworthy here is that they found four different completely dissimilar proteins with the function, which would have been undetectable as being related in any BLAST or other similarity-based search). Later experiments revealed that under certain conditions, the protein also catalyzes ATP hydrolysis to ADP.
A version of the original experiment was repeated by another lab, and results published in 2015. This time they used a smaller subset (15) of the 20 known biological amino acids, biased towards the set of amino acids thought to be prebiotic, and found additional proteins capable of ATP binding and hydrolysis.
The Tawfik lab constructed a super simplified facsimile of the inferred ancestor of the P-loop NTPases, called the Walker-A P-loop motif. The protein is only 55 amino acids long, yet functional, in that it could bind and hydrolyse ATP(and other NTPs), bind RNA and DNA.
That function really does seem to be hyperabundant in protein sequence space.
Yep. Gil doesn’t seem able to shift out of this “Gpuccio gives me this number, prove him wrong or he’s right by default”-mode of thinking.
Just more “But this one goes to 11.”
Predictably, Gil hasn’t explained why “FI” isn’t perfectly analogous to Nigel’s amplifier knob.
While on the subject of P-loop NTPases, the extreme functional diversity of that superfamily of proteins shows that functional protein sequence space is actually highly interconnected, and different functions are overlapping. The same protein sequence and structure can harbor many different functions, and functions can be incrementally derived from each other with relative ease by mutations and natural selection.
You are missing the mark here for I was not talking about the whole ATP synthase but only the beta chain that happens to exhibit a high degree of conservation from bacteria to human. So why are you trying to muddy the waters here by invoking other subunits?
You appear to misunderstand me, I was not speaking about the whole complex. What I wrote is true for the beta subunit considered in isolation. It really is the case that it is highly divergent across the tree of life, and that different ATP synthases have different beta subunit sequences.
And not overlapping too. The myosins, the kinesins, and the G proteins are all P-loop NTPases. The same protein fold at the core.
This is why @Agauger’s going on about “functional folds” made no sense.
Related: I just read about this
”To kick-start the i5k, a pilot project was launched at the Baylor College of Medicine led by Stephen Richards to sequence, assemble, and annotate the genomes of 28 diverse arthropod species carefully selected from 787 community nominations.“
“ The team’s analyses focused on tracing gene evolutionary histories to estimate changes in gene content and gene structure over 500 million years. This enabled identification of families of genes that have substantially increased or decreased in size, or newly emerged or disappeared, or rearranged their protein domains, between and within each of the major arthropod subgroups. The gene families found to be most dynamically changing encode proteins involved in functions linked to digestion, chemical defence, and the building and remodelling of chitin – a major part of arthropod exoskeletons.”
“ We can take these hypotheses into the lab and use them to directly study how the genome is translated into visible morphology at a resolution that cannot be achieved with any other animal group,” says co-lead author, Ariel Chipman, from the Hebrew University of Jerusalem, Israel.
Santa Clause has more evidence for existence that does ID-Creationism. 
I predict that a Gish Gallop is forthcoming…
What wouldn’t have a marginal impact on FI?
The level of polymorphism
What level of polymorphism would be a problem for FI, and why?
After reflection, I can see that I’m not quite sure to understand your question. Can you precise what you mean?
What would have a major impact on FI relative to ID?