Dr. Winston Ewert put forward his module hypothesis, but I put forward an alternate module hypothesis at the domain and motif level of proteins. It is based actually on papers by evolutionists who have pointed out that the problem of “Promiscuous Domains” remains an unsolved problem in evolutionary biology.
When I put Promiscuous Domains on the table in the Common Design vs. Common Descent thread, the TSZ Darwinists ignored the problem and then declared victory. I viewed their non-response as evidence they didn’t understand the problem and/or preferred to ignore it.
Perhaps pictures are worth ten thousand words. From the NIH, that great source inspiration for the Intelligent Design community, we have the CDART database viewer.
From the CDART viewer, I provide a few of the thousands of diagrams that show the promiscuity of protein domains. The diagrams below show the classical zinc finger ZF-C2H2 “ZF” domain and the Plextrin Homology “PH” domains. Note how the location of domains is “shuffled” to different locations in different proteins. It’s as if proteins are made by different lego-like parts in different order and position. My preliminary look into small 4-amino acid motifs that are the target of phosphorylating kinases suggests the the problem of promiscuity goes all the way down to small motif levels.
Such promiscuity is more consistent with common design than common descent.
Click to Enlarge Classical ZF-C2H2 Zinc Finger Page 5
Click to Enlarge Classical ZF-C2H2 Zinc Finger Page 157
Click to see all CDART Classical ZF-C2H2 Zinc Finger Architectures
That goes for anything, living organisms included as my grey fox example just demonstrated.
You are making my point for me
peace
Perhaps we should all insist on Sal being too fond of the false dichotomy, despite numerous attempts at helping him out of it. Maybe we should insist that he’s forgetting selection time and again. Maybe then he’d have to acknowledge the corrections. I told him trice already. No answer. Maybe Sal’s life depends on never acknowledging such a thing.
see folks? FMM can’t read for comprehension
😉
peace
I don’t know what you mean by “look like the result of random mutation” as it isn’t clear what that entails. How do you think phosphorylation sites being the result of random mutation would look like, and is there a role for selection to be played there? Are there some functional and structural constraints that could bias such sites away from, say, an equiprobable distribution across the length of a protein’s sequence?
Let me put something out there as factors that might explain why phosphorylation sites for PTM would be constrained towards particular similar areas on different proteins: PTM sites are more likely to emerge on sites where the sequence is already closely similar to a PTM motif. This one is just basic probability. If the PTM site has the amino acid sequence NKSQ to pick something out of a hat, an area of the protein that has a sequence similar to this (like NKSV) is more likely to turn into NKSQ by random mutation, than something that is more different (like AQSV).
So similar proteins with similar (even if not identical sequences) thus have more similar probabilities of evolving PTM motifs in similar positions even if they should do so independently.
A second factor: The order and direction of peptide chain synthesis during translation and protein folding. The n-terminus of proteins leave the ribosomal exit tunnel first, and thus are available for post-translational binding and editing, and chaperones, before the c-terminus.
That suggests to me that we should generally expect that mutations that inadvertently create phosphorylation sites inside folded proteins where editing enzymes can’t reach, would not be maintained by selection as they never have the opportunity to gain functions. So even if accumulation of random mutations happen to create a motif that has the potential for PTM somewhere in the core of a folded protein, it would eventually degrade again by further mutations as the site is never exposed. And the same goes for a preference for the n-terminus over the c-terminus.
That would, as such mutations crop up over time, at the very least bias functional phosphorylation sites towards particular exposed surfaces on the folded protein, or towards the terminus that is most easily accessed during and after translation. Similar proteins that fold in similar ways have similar areas exposed on the surface, are synthesized in the same order, which would also be the same areas that thus have at least the potential to gain a functional phosphorylation site.
And then it is more parsimonious to suppose such a motif in so far as it is similarly shared among many proteins of the same family, evolved once in the earlier evolutionary history of a protein, and was subsequently inherited by the descendant proteins that make up the family, rather than it having to evolve independently multiple times in different lineages.
So in summary, I suggest that there are certain structural, sequence, and mechanistic biases in how proteins are synthesized by the translational apperatus, that would explain why PTM motifs aren’t just “all over the place” at a roughly equiprobable distribution across protein length and sequence (supposing that is what you mean by “looks like the result of random mutation”), but instead seem constrained towards particular and similar areas and sequences on different proteins.
Do you understand?
All that seems like nothing more to me than dodging the question.
No, I said nothing like that.
Phenotype isn’t a character; it’s a huge collection of characters. Anyway, there are very few cases in which analyses of phenotype differ from analyses of DNA.
Again, I admitted no such thing. Heritable vs. not isn’t a question of fit.
It would seem to me that if you aren’t denying a nested hierarchy, singular, then you can’t reasonably deny that it’s objective, i.e. discoverable rather than imposed. And if you think special creation would exhibit a nested hierarchy, please provide a reason why it should. There are excellent to suppose that common descent would, but I can’t think of a reason why separate creation should, and nobody else has advanced one either, so far. Be the first.
If you think so, you don’t understand what I’m saying. One can’t find an objective nested hierarchy by picking features for fit to a particular tree, nor by applying features in some order. One can of course do such a thing with any data. But one could not do the real analyses we do to find objective nested hierarchies with just any sort of data, and those analyses don’t involve such biased, result-driven methods. We do not choose data to support a foregone conclusion (and that’s not why we pick heritable characters) and we don’t pick characters in any sort of order: we consider them all simultaneously.
I wouldn’t be surprised if the Discovery Institute shows a keen interest in TopIsomerases. Sooo, maybe someone there will be interested in these diagrams since the idea of PTMs was something Johnathan Wells emphasized in his writings.
Anyway, here is the next adjacent segment on the Top2 proteins:
Click to ENLARGE
Here is the next adjacent segment, there will be about 9 more to go….
Click to ENLARGE
Actually, the previous comment was in error, this is the correct diagram:
Click to ENLARGE
Well, let’s consider what would happen if say an ape had it its womb an act of special creation that gave rise to a human boy. Oops, I suppose there would be a problem, since there had to be available a baby human girl. Oh, wait, you seem to think changing a species with brand spanking new features is just a matter of a few mutations. You totally don’t account for the need of coordination in the mating partners.
This would probably be almost as shocking to the ape parents to have a human boy as a human couple having a gorilla for a son, and the son would have no mate. We call this a “hopeful monster” (ala Godlshmidt and Gould). Yeah, LOL, indeed.
Here’s the next adjacent segment. One will notice the density of PTMs is smaller in these segments. Because Topisomerases are the targets of anti-cancer chemotherapies, the fine details of this enzyme are constantly studied by many labs and there are thousands of papers. I visited a lab that studied Topos and learned from one of the researchers that this portion of the protein is likely on the inside of the fold. Hence it is not surprising the scarcity of PTMs.
Click to ENLARGE
Always a male first huh?
In either case yeah that’s amazingly ridiculous. If invisible incorporeal magic man by the power of merely wishing for it really hard, turned a primate fetus into a human one, magic man would have to do it twice, and then hope the population doesn’t collapse to inbreeding, or intervene some more. Which is silly I have to agree. I guess we can reject special divine intervention in the womb.
Any single “mutant” on the transition from the common ancestor we share with the chimpanzee (which is therefore not a step from the chimpanzee itself), towards ourselves, would probably be almost indistinguishable from whatever standing variation was in the then-extant hominid population at the time. Evolution is something that happens to populations over many generations. Evolution is not contingent on a gorilla suddenly giving birth to a philosopher poet one day.
You’re being intentionally silly right? Even you must be aware that evolution doesn’t say that there was once something like one of our primate cousins that suddenly gave birth to modern homo sapiens.
I’m adding an enhancement to the last segment to show the catalytically active sites as reported in Uniprot:
Attached is the next adjacent segment. Note there is only 1 PTM. The active sites are highlighted in red. As predicted the active site had high (in fact 100%) conservation!
Click to ENLARGE
1) I don’t deny that organisms can be placed in a nested hierarchy like any thing that can be categorized
2) I don’t deny that organisms like anything that can be categorized has at least one objective nested hierarchy (the one that exists in the mind of God)
3) I don’t deny that God can reveal the objective nested hierarchy of anything that can be categorized to us if he chooses to.
Your lack of imagination is not an argument. That is not how this works
You need to demonstrate why special creation would not form a nested hierarchy. Good luck with that
I think you haven’t been paying attention. It’s really pretty simple
1) Anything whatsoever that can be categorized will form a nested hierarchy
2) Any nested hierarchy that God produces will be an objective nested hierarchy by definition.
The balls in your court to show why that is not true
It’s your claim after all
peace
By what definition?
Presuppositional bullshitologists like FMM define “objective” as anything done by their imaginary magical being in the sky. He’s equivocating, which isn’t too surprising from that kind of Christian.
More content, less abuse, please.
You seem determined to obfuscate as much as possible. “I’m not denying the nested hierarchy” is quite a different statement from “I don’t deny that organisms can be placed in a nested hierarchy like any thing that can be categorized”. Are you doing this on purpose, or are you just incapable of saying what you mean?
In that case, why have you been denying that organisms have an objective nested hierarchy? It’s impossible to talk to you.
Are you now saying that everything has an objective nested hierarchy?
Perhaps. But the inability of anyone at all to come up with a reason does seem to be an argument to me. I suppose you have no interest in science, but in science it is necessary for a hypothesis to have expectations of what the data will and will not look like.
So what you’re saying is that we can have no expectations of what kind of signal creation would leave in the data. I agree. This is why it’s useless to consider it as a hypothesis. Since we do expect that common descent will produce a nested hierarchy and we have no expectation that anything else would, when we observe nested hierarchy we provisionally conclude that there has been common descent. You may choose to believe that it’s really creation that just happens to look like common descent, just as you may choose to believe that a duck is really a walrus that god has formed into the semblance of a duck. But it’s not something we can discuss rationally.
What do you mean by “will form”? That makes it sound inevitable and objective. But since you have both confirmed and denied that there are objective nested hierarchies, I can’t tell, so I can’t evaluate claim #1.
I have no idea how you could possible support claim #2. By definition? Why? But if God has produced the nested hierarchy of life, isn’t it therefore an objective nested hierarchy? If so, why have you denied that it is? What did you mean by all the crap about gray things?
The ball’s in your court to say anything sensible, coherent, and clear. I can’t address this morass of self-contradiction.
You have introduced a strawman version of guided evolution to go along with your usual strawman version of unguided evolution. Who says that guided evolution must proceed by saltation? Are you saying that the human genotype is so completely integrated that every difference between humans and the human/chimp ancestor must be introduced at once? If so, what’s your evidence for that claim? If not, why bring up the silly strawman?
Here is the next adjacent segment of the Top2 proteins. I’ve learned a lot in the process of gathering this information and have had some thoughts about promiscuous motifs in biology as I surveyed the target addresses of PTM motifs.
Topos are an extremely complex machine with promiscuous domains in them. The point of the present posting of the diagrams is to serve as a starting point for promiscuous motifs that are much smaller than the promiscuous domains.
Click to ENLARGE
How small are these promiscuous motifs? If they’re small enough, what would make you suppose that they couldn’t arise by random mutation, possibly with selection?
Agree, it’s something I’m thinking about. The motifs are 4 amino acids long. I found that to be extremely small!!! However, the Protein Atlas of Kinases said certain kinases target motifs that small!
So, if they’re that small, I repeat: what would make you suppose that they couldn’t arise by random mutation, possibly with selection? Would they not occur fairly frequently in strings of random amino acids, especially if some of them are high-frequency residues?
I already acknowldged your concern as valid, however, the question arises, given such small motifs could arise by chance how these kinases aren’t mis-targeting proteins and putting PTMs where they shouldn’t be and removing PTMs where they should be. But this isn’t a problem if the system is designed and created.
So the concern you raise is legitimate, but it is also a two-edged sword.
For completeness, this the paper I tracked down from UNIPROT as the source of some of the phosphorylation experiments that I used to generate the PTM diagrams of Top2.
http://www.pnas.org/content/105/31/10762/tab-figures-data
The motif of interest is called:
Aurora kinase A motif. However, as I looked into it, some of the actual kinases that implement the motif are kinases like CSNK2A1 which targets “rkps”.
That said, there are about 500 kinases in humans and maybe tens of thousands of motifs. An open problem is begin able to define the “logo” the kinases target as a single kinase will target more than one motif.
Who says that kinases aren’t mis-targeting? Have you investigated that? It looks, in fact, as if your 4-amino acid motifs don’t actually exist. There seem to be some common sequences at phosphorylation sites, but they also seem to be both non-universal, fewer than 4 amino acids, and often non-contiguous.
Doesn’t actually follow.
What you mean is that it’s not as specific as you initially claimed.
Incidentally, I was unable to locate “RKPS” in the reference you cited.
Look at Table S5, you’ll find it in the excel file. You’ll see Top2A in that list.
You’ll find it on row 296 under the column that says “motif”
http://www.pnas.org/highwire/filestream/596660/field_highwire_adjunct_files/4/SD5.xls
stcordova,
Is that a conserved and repeated motif or just the sequence that happens to be at one particular phosphorylation site? It seems that every site in that table is a site for the same kinase, so the specificity isn’t anything near what you have been claiming. In fact only the serine seems invariant, which makes sense. Or am I reading the table wrong?
I should mention many of the PTMs that involve sumolation and ubiqutination are cross link sites important to protein structure. I don’t think these motifs and locations can be subject to much random mutation without compromising protein structure. Here is a discussion of polymer cross linking:
https://en.wikipedia.org/wiki/Cross-link
In the process of looking up cross linking, I found an error in one of my diagrams. I listed a PTM as K1469ub, it should be K1459ub. That is also the location of a crosslink site. So again, even under the consideration of cross link sites that have associated SUMO and Ubiquitin modifications, how much random mutation can those small motifs tolerate?
I’ve focused a lot on kinases that are the “writers” to phosphorylation sites, but what about the writers to Ubiquitin and Sumo sites? Apparently the Designer can modulate subtle conformations of the protein by affecting the crosslinks with PTMs!
If I have claimed such specificity, I was clearly in error. Thanks for pointing that out. However, the problem of coordination still stands. The “rkps” motif was targeted only during the M-phase, the other phosphorylation sites on Top2 were not on that list, so that tells me the PTMs are cell phase specific.
I’m not prepared anything “that tells me”, given your observed tendency to misinterpret what you see. (Witness the most recent error.) Now, if you could discover the mechanism by which that particular kinase recognizes different motifs at different times, that might help.
And this has absolutely nothing to do with separate creation of species vs. common descent.
Suit yourself, but much of what I said is in the literature. Maybe you can learn something for a change and stop pretending you have mastery over this material, because you clearly don’t.
https://rockland-inc.com/post-translational-modification-antibodies.aspx
And if you’re going to nit pick, I’ll point out you missed the “rkps” motif in the paper I linked. I had to point it out to you since you couldn’t find it yourself.
https://rockland-inc.com/uploadedImages/ProductsStatic/post-translational-modifications-ptm.gif
Never said I did. I only say that you don’t.
That’s because it isn’t there. You have to follow the link through another link. Wait, I take it back. There’s no link either. I don’t know how you get from the link you gave to the Excel file; I can’t even tell if it’s part of the same paper. Or are you possibly referring to “Data Set S5”?
I’m going to eventually post the collection of Top2 diagrams in better screen resolution than what TSZ wordpress is capable of rendering. I will also go back and add crosslink data to the diagrams.
That said, here is the next adjacent diagram. I hope to provide this data to some in the ID community, such as the Discovery Institute.
Click to ENLARGE
Any definition that acknowledges that God is a being worthy of worship.
In other words any definition that is not nonsensical or illogical.
peace
here is the definition
quote:
expressing or dealing with facts or conditions as perceived without distortion by personal feelings, prejudices, or interpretations
end quote:
from here
https://www.merriam-webster.com/dictionary/objective
As you can see there is no equivocation whatsoever.
peace
I don’t believe those statements are “quite different” and I should know since they both reflect my view on the subject.
I think you are unintentionally reading stuff into what is being said that reflect your own views instead of the intended meaning.
I never once said that. What I said was that you can’t demonstrate that your chosen nested hierarchy is objective while others are subjective.
I gave a reason so I guess your “argument” is defeated.
I have absolutely no idea how you came to that conclusion.
Creation can be expected to leave a very particular sort of “signal” simply because the peculiarities of a creator will be evidenced in what he creates.
I mean simply that nested hierarchies are necessary artifacts of the categorization process. You can’t categorize with out them.
In the future I hope that you will pay as much attention to what is actually being said as you do to your own ideas as to what the underlying meaning is.
Saying that you can’t demonstrate that your nested hierarchy is objective is not denying that an objective nested hierarchy exists.
not by a long shot.
again It’s literally self-evident once you understand the definitions of God and objective
I was simply pointing out one of the myriads of ways one can construct a perfectly valid and useful nested hierarchy that will conflict with the one you claim to be objective.
peace
fifthmonarchyman,
Nowhere in that definition is there anything about an imaginary being’s wishes, thoughts, and actions being called “objective.”
The reason for calling those nested hierarchies “objective,” has nothing to do with imaginary beings, and everything to letting the data “talk.” The hierarchy is not obtained by forcing the data, but by following the data. That’s not the same kind of “objective” as a hierarchy “in the mind” of some magical being. Therefore the equivocation.
Of course I understand that if the magical being wasn’t the imaginary absurdity that it is, and preordained that the data should look as if evolution took place, the data would still “talk” by itself, and still be what the magical being had “in mind” (I’m puking as I write that shit, how can you stand that smell?), but you’re equivocating in order to shift the burden of proof, and in order to avoid the question: why would independently created life forms fall into a nested hierarchy the way evolved life forms would? Just calling any hierarchy “objective” for being “in the mind” of a magical being doesn’t answer the question. It just equivocates.
God is not an imaginary being.
He is a being worthy of worship. As such his opinions would necessarily be free of distortion by personal feelings, prejudices, or interpretations
That is logic 101
“Data” is not a person it can’t talk.
Data by it’s very nature requires interpretation by persons.
By their very nature non divine persons are biased and their interpretations are subjective.
again this is logic 101
I’ve already answered this one.
Perhaps you should go back and reread it. Any creation by God that can be categorized will necessarily form an objective nested hierarchy. There is no way to avoid it as far as I can tell.
If you have any specific questions I’d be happy to answer them
peace
You actually think that data “talks” and I am the one who is supposedly equivocating.
You couldn’t make this stuff up if you tried
peace
Of course it’s imaginary. It’s so absurd that it cannot exist. This is logic 101.
I read what you wrote. I even predicted your “answer,” so I was very clear in which way the hierarchy is called objective, so you’d be able to focus (as if a presuppositionalist would ever do that, equivocating in your whole purpose in life, for your imaginary friend’s glory, of course).
Again, you’re dismissing the way the hierarchy is said to be objective. Your “objective” it not the same as the objective used to describe the hierarchies obtained in evolutionary studies. You need to learn to read for comprehension. It’s not about dictionary definitions vs presuppositionalist definitions. It’s about the reason why those hierarchies are called objective. Again, because they’re obtained by following the data.
(I know data cannot talk, maybe you didn’t see those quotation marks, maybe thinking your god’s thoughts after “Him” doesn’t work very well, precisely because your god is imaginary).
Why this hypocrisy? You’re not happy to answer. You’re happy to insist on your equivocation, before acknowledging that you were “mistaken.” All for your imaginary friend’s glory. How’s that glorious to your imaginary friend, only you can know.
No, I couldn’t. I’d never think that someone who presumes of holding to the ultimate philosophy of philosophies, perhaps of thinking a magical being’s thoughts after “Him,” would prefer to look stupidly unaware of metaphorical language, twice, just to try and “score” some ridiculing “points.”
ETA: For your imaginary friend’s glory, of course!
fifthmonarchyman,
I find it very difficult to believe that anyone who was truly interested in and competent at communication would be so obscure. I will not at this time speculate on whether you are uninterested or incompetent. Or of course both. But I just want to point out that if your aim is communication, it isn’t being achieved.
You perhaps think you gave a reason. But it isn’t a reason.
Perhaps that’s true. It’s because of the meaning a reasonable person would attribute to the things you say. What you think is logically implied by what you say is seldom actually implied by what you say. You appear to have a private language that resembles English only in that the words are spelled the same. Does that help?
What pecularities are those, and why do they result in a nested hierarchy?
Not true at all. There are a great many categorizations that aren’t nested hierarchies. The periodic table. Rocks. May sorts of categorizations don’t have groups within groups, or have overlapping groups. You might want to look at the Quinarian taxonomic scheme.
Now that is a claim I’d love to see you defend.
Care to start an OP??
Of course I’m dismissing an argument that relies on Data “talking”.
Of course if you want to explain how data filtered through the biased and subjective lens of human interpretation can ever be said to be objective with out massive equivocation I’m all ears.
care to give it a go??
Data isn’t a person it does not lead anywhere so it can’t be followed. Please take a minute and think about what you are writing.
If the language is metaphorical then it won’t be a problem making your point using literal terminology.
You need to explain how objectivity can be achieved by subjective human interpretation of selectively chosen impersonal and “mute” data
again I’m all ears
peace
That is just your subjective opinion and saying something does not make it so.
You need articulate why my reason does not qualify.
there are lots of pecularities
The peculiarity that leads to an objective nested hierarchy is the unique ability to objectively classify things.
Not every categorization is a nested hierarchy. But any categorization can be part of a nested hierarchy.
The elements nest quite nicely with compounds and mixtures into the larger set called matter.
Igneous, Sedimentary, Metamorphic
each of those general categories are subject to further division
check it out
https://en.wikipedia.org/wiki/List_of_rock_types
I never said otherwise.
You are apparently confusing the ability to classify anything in a nested hierarchy with the necessity to do so.
peace
fifthmonarchyman,
Sorry, it really is impossible to talk to you. Perhaps I’ll try again later.
This is the next adjacent segment on Top2. Note the cross links are in the Top2A isozyme, but not in Top2B. This could be simply a lack of data, or that for whatever reason Top2B doesn’t have the same cross links as Top2A.
Click to ENLARGE