Gil grabs some ammunition and shoots down Doug Axe's 2004 extrapolation by a factor of more than 10^44

You’re stating that he cannot calculate it yet the evidence for different functional sequences you claim is there is based on evolutionary theory and not being their factually. I think this is what Koonin calls an adaptionist “just so” story.

He shows that you can have an exorbitant number of solutions and his claim still holds.

His calculation is meaningless because you believe the “just so” story is true. What if the “just so” story is false?

No, it’s based on the very same thing you are using to derive FI: sequence similarity.

You either accept that you can infer a homologous relationship based on nesting hierarchical structure in similar sequences, or you do not. If you make an estimation of FI based on similar sequences found in some database, you have implicitly accepted that the sequences are related. And thus that homology can be established from tree structure in similar sequences.

You can’t then suddenly and arbitrarily turn around and insist the method is “theory” and “just so story” when that VERY EXACT SAME METHOD is used to show ancestries deeper and more divergent than you are using it for. Then you are having your cake and eating it too.

I think this is what Koonin calls an adaptionist “just so” story.

LOL. Guess who co-authored this phylogenetic analysis of the entire P-loop NTPase superfamily of proteins?
eipe DD, Koonin EV, Aravind L. Evolution and classification of P-loop kinases and related proteins. J Mol Biol. 2003 Oct 31;333(4):781-815. DOI: 10.1016/j.jmb.2003.08.040

Bill you either accept phylogenies as evidence for homologous relationships, or you don’t. When you are doing FI calculations based on extrapolating tolerated variation from alignments of similar sequences, you have already accepted that. So using that very same evidence, we can show the evolutionary histories of the proteins in question go back, incrementally, to even simpler stages, some times with different functions and even structures.

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Sometimes the sequences are not so similar. We are looking at sequences based on similar or the same function. Beta lactamase is an example of a protein that has similar function but divergent sequences.

So what?

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Your claim:

Is false.
We are looking at similar function.

No, it’s not false. Many (actually the vast, vast majority) of the functional annotations found in databases are based on sequence similarity(some times including surrounding gene and non-coding DNA synteny), scientists have generally not re-done the complete experimental biochemical assays that show the actual biochemical functions of these proteins for every new species they are discovered in.

And even where they have done assays that show the functions of different proteins, Gpuccio has not been deriving his numbers from different proteins with similar functions. He’s just done blast searches looking for proteins with similar sequences.

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This is not the method we are using. The function of alpha actin is clear as the function of beta lactamase is also clear. One protein lines up well the other does not. The comparison is based on functional similarity not sequence alignment. I understand the maturity of the databases is an issue for certain comparisons.

This is false. You need to rethink your argument.

Hey, it gets worse. Gpuccio implicitly accepts the inference of incremental increases in protein size and complexity over the history of some clade. That’s how he derives his so-called “information jumps” from for example the evolution of some protein in an inferred ancestral vertebrate, to the human version of the sequence.

Hence Gpuccio implicitly accepts that this historical growth has occurred, and has an even deeper ancestry. Read the link.

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Yes, that is the method you are using. You clearly have no idea what’s going on, again.

No, it’s not false. Please go and read what Gpuccio actually does, from his own posts. Click the link above.

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After re reading this I see where you are coming from. He is looking at basically the same function and not similar function. I think this is where the disconnect is. Where I think you are still in error is claiming that

The sequences may be similar and may not be. It depends on the variation observed from the specific function in different animals.

No the disconnect still is that you don’t understand that his method is based on similarity searches, because he literally explicitly does similarity-based searches when he’s looking for homologous sequences in other species to the one he’s interested in.

There isn’t any way around this.

But I’m not, for reasons already explained.

Your subjective views on the degree to which the sequences are “similar” is not a relevant factor here Bill.

What matters to the question of whether the method is based on similarity or not, is how Gpuccio finds and includes a sequence to use so as to extrapolate the amount of tolerated variation for some sequence to implement a function. He does that by doing similarity-based searches. That is what happens when you use a BLAST search tool.

Even were he to use names of proteins from different species(in other words lets say he tries to avoid using blast), say he wants to find ATP synthase subunit beta in some unicellular eukaryote, he could just be searching for that (“ATP synthase subunit beta”) on uniprot for example, and then choose to sort results by taxonomy. He’d find lots of candidate gene sequences that haven’t actually been experimentally characterized to be ATP synthase subunit beta, but merely inferred to be that merely on the basis of some sort of similarity measure. That’s how these genes are often times automatically annotated in these databases.

Only a very small subset of them have been experimentally characterized to function in some specific way expected from their similarity.

Now since these BLAST-based searches used to collect homologous sequence for use in the extrapolation of FI, are in fact based on sequence similarity, and since this in turn means that to calculate FI you are implicitly accepting that the similar sequences you use in your calculation are in fact homologous, then it will be hypocritical to suddenly arbitrarily reject similarity-based inferences of relatedness when those very same similarity-based searches can be used to show deeper ancestral relationships to proteins with different functions, or with simpler structures and shorter, more likely sequences.

You can’t have your cake and eat it too.

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His claim has nothing to do with functional information.

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How many different types of beta-lactamase are there, Bill? Are all of their sequences homologous?

How are you doing on coming up with a design explanation for all of those MYH7 alleles in healthy humans?


According to Bill, such experiments can be dismissed as “just so” stories. :smile:

No the disconnect still is that you don’t understand that his method is based on similarity searches, because he literally explicitly does similarity-based searches when he’s looking for homologous sequences in other species to the one he’s interested in.

The sequences in invertebrates are very different here. How does your argument work?

Gpuccio found them by similariy-based BLAST searches. So, that’s how.

Are you claiming that these are different functioning proteins?

No, why would I? LOL


How then are they labeled the same function with vastly different sequences?

Because they’re still similar enough for that inference to be made. Similarity comes in degrees Bill, it is not only 100% or 0%. There are significant similarites below 100% and above 5%, for protein sequences. Heck, there are even significant sequence similarities at 0%(no identical residues in pairwise alignment), I’ll let you figure out how that can be.

Try going on uniprot and pulling up a lot of homologues of ATP synthase subunit beta, and you will discover that only for a small minority do they have experimental biochemical evidence for the function of the sequence. It’s the same for all of these public sequence and genome databases that have gene sequences from millions of genes from hundreds of thousand of species. There’s no way to biochemically assay and characterize all these millions upon millions of genes, so functional annotation is often times automated by similarity-based algorithms, or some times even mere alignments by hand.