What is evolutionary theory?

[colewd (Bill Cole)]

@T_aquaticus

Even random proteins will have folds.

Without serendipity 2500 AA structures do not fold into a functional secondary structures such a alpha helixes and beta sheets.

@T_aquaticus

How do you determine how many sequences will have activity?

You determine the activity then you estimate the substitutability of each AA location. Activity does not equal biological function.

[colewd (Bill Cole)]

@John_Harshman

You will have to explain what that means.

MG+ levels vary depending on the condition of chromosome structure. They are highest during meiosis where chromosomes are tightly wound. The spliceosome can operate in these variable MG+ conditions.

[John_Harshman]

@colewd

MG+ levels vary depending on the condition of chromosome structure. They are highest during meiosis where chromosomes are tightly wound. The spliceosome can operate in these variable MG+ conditions.

You’re going to have to do better than that. Present some kind of argument rather than hinting at something you might say.

[colewd (Bill Cole)]

@John_Harshman

You’re going to have to do better than that. Present some kind of argument rather than hinting at something you might say.

John, there is experimental science behind this argument. High Mg+ conditions are required for type 2 introns to operate properly. Eukaryotic cells have variable Mg+ conditions.
https://doi.org/10.1016/j.cub.2017.12.035

[John_Harshman]

@colewd

John, there is experimental science behind this argument.

Don’t all cells have variable Mg+ conditions? Don’t eukaryotes have group II introns? And what argument? You haven’t made an argument yet. Come on, Bill. Try for once to present a coherent, complete argument supporting a clear claim.

[colewd (Bill Cole)]

@John_Harshman

Don’t all cells have variable Mg+ conditions? Don’t eukaryotes have group II introns? And what argument? You haven’t made an argument yet. Come on, Bill. Try for once to present a coherent, complete argument supporting a clear claim.

The condition unfavorable to Mg+ occurs in the cell nucleus. This is where type 2 introns do not effectively splice. This supports the chicken and egg problem as the conditions in the cell nucleus require the spliceosome.

I have supported the claim the “you got to do better then that tactic” is duly noted.

[Timothy_Horton]

@John_Harshman

Don’t all cells have variable Mg+ conditions? Don’t eukaryotes have group II introns? And what argument? You haven’t made an argument yet. Come on, Bill. Try for once to present a coherent, complete argument supporting a clear claim.

Bill likes to repeat words and phrases he picks up from EN&V and UD. He usually doesn’t understand what they mean, can’t even begin to defend them, but they’re WORDS! From an AUTHORITY! That’s all an ID-Creationist needs.

[T_aquaticus]

@colewd

Without serendipity 2500 AA structures do not fold into a functional secondary structures such a alpha helixes and beta sheets.

That needs some evidence to back it up.

Added in edit:

Biological proteins are known to fold into specific 3D conformations. However, the fundamental question has remained: Do they fold because they are biological, and evolution has selected sequences which fold? Or is folding a common trait, widespread throughout sequence space? To address this question arbitrary, unevolved, random-sequence proteins were examined for structural features found in folded, biological proteins. Libraries of long (71 residue), random-sequence polypeptides, with ensemble amino acid composition near the mean for natural globular proteins, were expressed as cleavable fusions with ubiquitin. The structural properties of both the purified pools and individual isolates were then probed using circular dichroism, fluorescence emission, and fluorescence quenching techniques. Despite this necessarily sparse “sampling” of sequence space, structural properties that define globular biological proteins, namely collapsed conformations, secondary structure, and cooperative unfolding, were found to be prevalent among unevolved sequences. Thus, for polypeptides the size of small proteins, natural selection is not necessary to account for the compact and cooperative folded states observed in nature.
Protein Folding Absent Selection, LaBean et al. (2011)

@colewd

You determine the activity then you estimate the substitutability of each AA location. Activity does not equal biological function.

How do you determine if a sequence has biological function?

[John_Harshman]

@colewd

I have supported the claim the “you got to do better then that tactic” is duly noted.

Whatever does that mean? Once again I encourage you to think before posting, try for coherence, and re-read for sense before hitting the “send” button.

[colewd (Bill Cole)]

@T_aquaticus

Libraries of long (71 residue)

The average human protein is 500AA long.

@T_aquaticus

How do you determine if a sequence has biological function?

By watching it function in a cell.

[T_aquaticus]

@colewd

The average human protein is 500AA long.

Then the chances of producing a protein fold are even greater. In random peptides just 71 amino acids long they found a large percentage had folds. In fact, the prevalence of folds in random peptides wasn’t that far off from the number of folds found in naturally occurring and functional proteins:

After subtracting the contribution due to ubiquitin from the library spectra, it was estimated that the random-sequences of LIB38 contained 23.6% α-helix and 20.5% β-sheet, while LIB71 contained 30.5% α-helix and 10.9% β-sheet. Interestingly, these estimates are within the range of secondary structure contents found in natural proteins [37].
Protein Folding Absent Selection - PMC

Nearly half of the short random peptides had secondary structure, either a beta sheet or alpha helix. So why are you saying that these features are rare?

@colewd

By watching it function in a cell.

What if I gave you a random sequence that was not found in a cell. How would you determine if it had sequence?

[colewd (Bill Cole)]

@T_aquaticus

Then the chances of producing a protein fold are even greater.

Whats the point? Some folded structure inside a peptide chain is meaningless unless it can obtain a functional tertiary fold.

@T_aquaticus

What if I gave you a random sequence that was not found in a cell. How would you determine if it had sequence?

I am not sure what you are trying to say.

[John_Harshman]

@colewd

Some folded structure inside a peptide chain is meaningless unless it can obtain a functional tertiary fold.

T_aquaticus:

And the goalposts go flying by.

[colewd (Bill Cole)]

@John_Harshman

And the goalposts go flying by.

When did I ever make a claim about a partial secondary structure irrespective of a tertiary structure?

[Mercer (John Mercer)]

@colewd

Whats the point? Some folded structure inside a peptide chain is meaningless unless it can obtain a functional tertiary fold.

Maybe you should read this paper before pontificating:

@T_aquaticus

After subtracting the contribution due to ubiquitin from the library spectra, it was estimated that the random-sequences of LIB38 contained 23.6% α-helix and 20.5% β-sheet, while LIB71 contained 30.5% α-helix and 10.9% β-sheet. Interestingly, these estimates are within the range of secondary structure contents found in natural proteins [37].
Protein Folding Absent Selection

Then please explain this paper:
https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.14012

[John_Harshman]

@colewd

When did I ever make a claim about a partial secondary structure irrespective of a tertiary structure?

Sorry, Bill. It’s hard to tell what you’re making a claim about. What you say right there, for example: What does it mean?

[T_aquaticus]

@colewd

Whats the point? Some folded structure inside a peptide chain is meaningless unless it can obtain a functional tertiary fold.

Your argument is meaningless unless you can bring some evidence to the table.

@colewd

I am not sure what you are trying to say.

What if I had a random sequence generator create a 100 amino acid peptide. Would you be able to tell me if that sequence has biological function by the sequence alone?

[colewd (Bill Cole)]

@T_aquaticus

Your argument is meaningless unless you can bring some evidence to the table.

You brought evidence to the table that didn’t show that a random sequence could create a functional secondary fold in order to start the process of natural selection. I was merely pointing this out. The problem of a 2500 AA sequence protein attaining a possible selectable sequence remains.

@T_aquaticus

What if I had a random sequence generator create a 100 amino acid peptide. Would you be able to tell me if that sequence has biological function by the sequence alone?

Probably not, however it depends on how you define “functional”.

[Mercer (John Mercer)]

@colewd

You brought evidence to the table that didn’t show that a random sequence could create a functional secondary fold in order to start the process of natural selection.

Bill, please apply your word salad quoted above to the fact that by selecting from a random library of immunoglobulin variable regions, we can find immunoglobulins with beta-lactamase activity.

What does the adjective “functional” mean in front of “fold” in this case; that is, what is the “functional fold” for those enzymes?

Do you not understand that “fold” is a structural, not a functional, classification?

[T_aquaticus]

@colewd

You brought evidence to the table that didn’t show that a random sequence could create a functional secondary fold in order to start the process of natural selection.

Random sequence formed beta sheets and alpha helices.

@colewd

The problem of a 2500 AA sequence protein attaining a possible selectable sequence remains.

That problem is squarely in your court. You are claiming that biological function would be too rare, and evolution would not be able to find it. That claim has yet to be supported.

@colewd

Probably not, however it depends on how you define “functional”.

If you don’t know which sequences would have function, however you want to define it, then how can you make any claims about the rarity of function in sequence space?