Gil's testable ID hypothesis

Continuing the discussion from Is ID science? Redux:

Gil, misrepresenting (hopefully not deliberately) his assumption as a fact, has provided a clear ID hypothesis in what appears to be the process of scrambling to avoid testing @gpuccio’s FI hypothesis:

No, I cannot, because the binding specificity of three-dimensional antibodies is a combinatorial function. You are now ignoring somatic hypermutation. You are also ignoring the sloppy joining of segments by recombination, which generates new FI in real time.

Again, @gpuccio’s hypothesis (misrepresented as a fact) is that there is an FI threshold that cannot be generated without design. This hypothesis makes testable predictions that @Giltil and @gpuccio seem to be uninterested in testing.

Your hypothesis is most clearly stated as:

Let’s test it together!

Hints:

  1. in those stem B cells, the gene segments that are recombined are arrayed like this:
    https://www.cell.com/fulltext/S0092-8674(04)00039-X

Let’s look at the heavy chain. Note that the cartoon is not accurate, as there are hundreds of V segments that can be recombined. Again, @Giltil’s very testable hypothesis is that most of the information is already there.

  1. The test can be done using genetic engineering of mice, in which we can insert, delete, or substitute pieces of DNA using embryonic stem cells.

Let’s be Socratic about this one. Anyone but @Giltil , feel free to PM me with your proposed test of @Giltil and @gpuccio’s hypothesis. Please post questions here.

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Hello, @Giltil. Let’s discuss here. This also might be something that @Jordan might want to consider as a teaching aid.

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It would also be helpful if @Giltil or some other ID supporter would describe how they are measuring functional information (FI). If we are using the definition and calculations I have seen before, then we should be comparing sequence between distantly related species and looking for regions of conserved sequence. It is only the conserved sequence which is though to contain FI. If this is not the definition being used, then the ID supporters need to supply the definition they are using.

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Or not measuring.

@Giltil has stated his hypothesis clearly:
“V(D)J recombination doesn’t produce high FI for high FI preexist in the stem cells that develop into B cell.”

Then appears to have hedged a bit:
« V(D)J recombination doesn’t produce high FI for most of the genetic information necessary for implementing the function preexist in the stem cells that develop into B cell »

Luckily, we can still test the hedged version.

Gil, let’s take a baby step. If we are to test your hypothesis that most of the genetic information preexists, what experiment do we need to do, stated simply?

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Okay. You may first isolate an hematopoietic stem cell from a given person and sequence it’s genome. You may then isolate from that same person a number of naïve B-cells and for each of them determine the sequences of the V regions of the cognate B cell receptor. Then, you may blast the sequences of the V regions determined in the different B cells against the sequence of the genome determined in the stem cell. By doing so, you will find that for every B cell investigated, most of the sequence of the V regions are already present in the genomic DNA of the stem cell. IOW, you will find that for every B cell produced within a given person, the genetic information coding for the V regions of the B cell receptor already exists in the genome of that person.

That will be true for almost every evolutionary pathway. You take DNA that already exists and slightly change it or shuffle the pre-existing sequences around.

What this shows is that ID supporters will reject any observation of the evolution of new functional information simply because it is a modification of already existing DNA. That’s ridiculous.

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You’re confusing information with sequence.

You can always break up any sequence of symbols into smaller fragments and rearrange them, producing a new sequence. But then someone like you can come along and declare that the sequence isn’t new, it’s just rearranged fragments of already existing sequence

I could rearrange
CACACAGAGAGA
into
GAGAGACACACA
And you’d say there’s no new information, because it’s just the first sequence broken in half and the latter half put before the former.

But we could do that again, beak it up into smaller bits like CA and GA, and rearrange them.
GACAGACAGACA
And you could still say no new information, because it’s still just rearranged already existing seqeunce. All the CAs and GAs were all there to begin with.

And we could do it again, break it up into individual letters A, G, and C.
CCCAAAGGGAAA
And you could still say no new information, because it’s still just rearranged already existing sequence. All those As, Gs, and Cs were there to begin wtih.

Which reveals the absurdity of what you’re saying. So no, rearrangement really is new information. That is the only sensible position to take.

The problem is that you haven’t defined what constitutes “new” information to begin with, that means you can just make up the rules as you go along and keep denying that any example we come up with counts as new information. And the one you seem to be working from here is absurd.

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You’re out of line here for we are not discussing an evolutionary pathway. Not at all. The issue is whether or not the genetic information coding for the V regions of the immunoglobulin receptors within B cells largely preexists in the genome of the stem cells that develop into B cells. What is your answer to this quite simple question?

According to the theory of evolution the genetic information coding for a species largely preexists in the genome of its precursor species. How is this different? Or do you wish to infer that evolution doesn’t require large quantities of new “functional information”?

(Many of the genes involved in animal multicellularity have been found to be already present in choanoflagellates.)

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Sure we are. If recombination of V(D)J regions does not count as producing new information then recombination of non-V(D)J regions would also not count as producing new information. If chopping up pre-existing DNA sequence into a novel sequence with novel function is not an example of new functional information, then what in the world would count as new functional information?

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Something that evolution could not produce. So if we find something that could arise thru evolutionary processes, then it is not new functional information. Because, see sentence 1.

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A good start, but I was referring to something far more experimental and far less descriptive–a more direct test of your hypothesis.

OK, but the V regions of naïve B-cells do not include the additional variation and refinement that we all know produces increased antibody function. So aren’t you missing a lot of differences?

That’s another problem. “Most of the sequence” is too poorly defined. Do you not know that some residues of the V regions are much more important for binding antigen than others?

Do you see that from my perspective, you appear to be hedging to try and defend your claim, in which you appear to lack confidence, while I am framing this more simply and less personally as testing a hypothesis?

No, “the genetic information” in your second sentence is not the same as “most of the sequence of the V regions.” That’s a very major movement of the goalposts.

Also, it’s better to frame predictions as “this hypothesis predicts” instead of “you will find.” Less risk to one’s ego.

Instead, how about something that uses either hematopoietic stem-cell transplantation or gene targeting with embryonic stem cells, so that we can be certain of eliminating most of the germline information, then testing immune function directly in whole mice instead of estimating it by BLASTing?

Wouldn’t that circumvent any ambiguities about how much sequence is “most,” and eliminate any disagreements about which residues are more or less functional, giving a clearer result? You do want a clear result, don’t you?

And in general, aren’t experiments far more rigorous tests of hypotheses than the descriptive work you’ve suggested?

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I don’t see any reason for you to claim that. This is rapid evolution of proteins with new functions. It even works to produce enzymes, for which it was not “designed.”

Heritable variation comes from recombination and mutation, the same places it comes from when proteins evolve over millennia.

The fact that most evolution skeptics choose to ignore the importance of recombination doesn’t justify claiming that a mechanism that derives much of its variation from it doesn’t represent evolution.

I think that “largely” is too vague to be useful in this context.

Another question. How do you rigorously define “largely”?

I’d also point out that fuzzy words like that make your question more complex, not “quite simple.”

And why not eliminate a known quantity of sequence and test directly for immune function? That would be a simpler, much more rigorous, and more quantitative test of your hypothesis, correct?

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Information that literally poofs into existence.

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Do you remember what I am saying? Let me recall you. My claim ( let’s called it claim G) is that « the genetic information coding for the V regions of the immunoglobulin receptors within B cells largely preexists in the genome of the stem cells that develop into B cells ». And you are saying that my claim is absurd. Okay. Now, what would say of this other claim (let’s called it claim S):
« In the genome of a germ-line cell, the genetic information for an immunoglobulin polypeptide chain is contained in multiple gene segments scattered along a chromosome ».
You will notice that both claim G and S have the same meaning. One is mine and the other is from Susumu Tonegawa, who won the Nobel Prize in Physiology and Medicine in 1987 for his discovery of “the genetic principle for generation of antibody diversity”. Now would you say that claim S from Tonegawa is absurd?
https://www.nature.com/articles/302575a0

Why are you blaming me for focusing only on VDJ recombination when it is you that challenge me on this very topic?


So no, I am not missing « the additional variation and refinement that we all know produces increased antibody function », I am simply responding to the point that you yourself put on the table.

Are you denying that the genome of a germ-line cell contains the genetic information for an immunoglobulin polypeptide?
If so, are you also denying that human genes contain the genetic information for human proteins?

(Sigh). ln the spirit of this group I am going to interpret your last comments in the most generous way possible, and presume that you simply misunderstood the arguments presented to you, and are not deliberately misrepresenting them.

The issue is not whether the genome of a germ-line cell contains information.

The issue is whether when the sequences are re-arranged to code for new proteins, this constitutes “new information.”

If your position is that it does not, then that leaves open two important questions that you have consistently failed to address.

  1. Exactly what would you consider to be “new information”?

  2. On what basis do you assert that evolution could not occur without the creation of this sort of “new information”?

Hope that helps.

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And as I wrote I think you’re confusing sequence, with information. And yes it really is absurd, because it leads to absurd conclusions as I showed with my example above.

The DNA sequences that will be translated into amino acid sequences exist already, yes. But that is not the same thing as saying that the information for the final product of translation, the immunoglobulin molecule, already exists. When speaking of recombination, you cannot predict merely from looking at the DNA sequence fragments, how they will end up recombined. The information simply isn’t there. The process of recombination thus generates that information.

You can only predict the amino acid sequence in fragments, from the individual DNA sequence fragments, but you can’t predict the fragment order, the product of recombination. You cannot tell me before recombination occurs how the final order of amino acids in the immunoglobulin molecule will look from C-to-N-terminal. You could at best make some probabilistic statement, but you’d basically just be making statistical guesses.

I would say that the statement can only be taken to mean the information for the amino acid sequence encoded by the DNA fragments that are to be recombined, is what is already there. But the information for the order of such recombined DNA fragments is not there, it is absent. It will be created when the process of recombination occurs.

If it is taken to mean that the information for the final order of amino acids that make up the immunoglobulin product can be “read” in the DNA of the B cell before recombination occurs, then yes it is absurd, because that simply isn’t the case.

Luckily, we do not have to interpret the statement that way. We can understand it simply to mean that the information for all the individual pieces of amino acid sequence that will make up the immunoglobulin protein, is already there. But the information about their final order, is not.

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