Freethought & Rationalism Archive

Nic Tamzek · 07-29-2003, 05:57 AM

For your reading enjoyment:

This was a discussion of Dembski's latest ridiculous claims about the literature, but has developed into another discussion of the immune system. I declared that I would drop out at my 999th ARN post (a ridiculous number already), which I did, but to my surprise rafe gutman has jumped in, exceeding my limited immune system erudition by, like, alot.

But what I find really interesting about these kinds of threads is how the ID argument gradually morphs from strong, bold claims (but easily proven wrong) into tenditious word salad. It's really quite fascinating.

http://www.arn.org/boards/ubb-get_to...00815-p-3.html
http://www.arn.org/boards/ubb-get_to...00815-p-4.html

jon_e, an earnest but (sorry to be frank, jon, if you read this) almost entirely clueless poster, seems to feel the need to raise objections almost just for the sake of doing it, whether or not he understands Behe's argument, or the immune system, or rafe, or even his own writing!

E.g., jon_e writes:

Quote:

Rafe,

quote:
--------------------------------------------------------------------------------

the advantage of an adaptive immune system is that it can adapt to the pathogen, within one organism's lifetime. as a result, organisms possessing such adaptive immunity can grow larger, live longer, have fewer offspring, etc. a human being wouldn't live very long without an adaptive immune system, maybe a year or so. however, 1 year is more than enough time for a sea urchin to propagate itself and fill any void left by the latest bacterial infestation.
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Thanks for reinforcing my point, rafe, as you did earlier when postulating an "immunological big bang." A sea urchin does not need the power of the adaptive immune system - however, the non-adaptive (non-rearranging-receptor-based) immune system DOES THE SAME THING as the adaptive, re-arranging-receptor-based system. That is, it targets antigens. Are you saying the innate immune system is NOT TARGETING ANTIGENS? Are you saying it's just a DIGESTIVE SYSTEM? Now let's look at this again . . . the sea urchin has these built-in receptors that are quite diverse, because they need to target a variety of antigens; the human immune system has these receptors that, because of its capability of rearranging genetic material "on the fly" as they're produced, can target an exponentially larger variety of antigens. Now, which one is more "powerful?" The human one, obviously, but only in matter of degree. So, my analogy: the sea urchin receptors are like "rifle shots" (all that is necessary for the sea urchin's lifetime/survival); the human receptors are like "shotgun-shell shot" - many more, aimed at many different types of antigens. But, if I'm not mistaken, they are essentially doing the same thing! Take away the ability to target the antigens, and "poof!" -the immune system no longer functions. Thus, the irreducible complexity of the system. You have got to show me somehow, NOT that the human adaptive system of rearranging receptors is a major innovation (it obviously is), or even that it is not IC (I don't know about that - Behe argues for it - fine - irrelevant to my point), BUT, (you need to show me) that the BASIC FUNCTION of the sea urchin's receptor system is FUNDAMENTALLY DIFFERENT from the BASIC FUNCTION of the human re-arranging-receptor system. (sorry for shouting...) If you don't, then you concede my point that removing either of those receptor systems from either of those immune systems renders those immune systems useless - thus IC.

But the argument that adaptive immunity is just an improvement added to innate immunity is an argument *against* Behe, because Behe said that IC systems have to come together all at once, or not at all. But jon_e is arguing *for* a position that undermines Behe, claiming that his argument supports Behe!

:banghead: :banghead: :banghead:

Unless I'm misreading the post entirely, perhaps someone else can make heads or tails of it?

PS: Perhaps there is some kind of Decreasing Coherancy Effect as threads advance and IDists try to maintain their original position, while incorporating the inconvient data presented by more informed posters earlier in the thread?

Principia · 07-29-2003, 06:45 AM

Nic,

<applause>

for your level-headed posts at ARN, and for lasting as long as you have. I'm willing to bet your 999 posts has denser information content than most of the other 1000+ posters there.

Now that you've declared a moratorium on posting at ARN -- just sit back and enjoy the ARNie show. You'll begin to realize just how inconsequential these people are. I mean, it's not like anyone expects the DI to show up at a school board meeting, point to ARN, and say "Look there. We have such great scientists and scientific discussion on our Internet forums, where even apologists and cranks are able to share the same stage and engage in productive dialogue."

Quote:

jon_e: You have got to show me somehow, NOT that the human adaptive system of rearranging receptors is a major innovation (it obviously is), or even that it is not IC (I don't know about that - Behe argues for it - fine - irrelevant to my point), BUT, (you need to show me) that the BASIC FUNCTION of the sea urchin's receptor system is FUNDAMENTALLY DIFFERENT from the BASIC FUNCTION of the human re-arranging-receptor system. (sorry for shouting...) If you don't, then you concede my point that removing either of those receptor systems from either of those immune systems renders those immune systems useless - thus IC.

This is the "Educate me please -- but only tell me what I want to hear" mode of argumentation, made famous by mturner. It's pointless. Go back to school, jon.

PS: I had time to reread jon's statement. Note the convoluted argument:

1) "You have got to show me somehow, NOT ... that it is not IC (I don't know about that - Behe argues for it - fine - irrelevant to my point)..."

2) "If you don't, then you concede my point ... thus IC."

This is the second mode of argumentation -- the I-win-by-default.

pangloss · 07-29-2003, 09:33 AM

Personally, I think Nelson has a learning disability....

caravelair · 07-29-2003, 09:48 AM

Quote:

Originally posted by Nic Tamzek
PS: Perhaps there is some kind of Decreasing Coherancy Effect as threads advance and IDists try to maintain their original position, while incorporating the inconvient data presented by more informed posters earlier in the thread?

i have observed this phenomenon first hand! i think you must be correct.

Albion · 07-29-2003, 12:40 PM

Sort of the opposite of irreducible complexity? Reducible coherence?

I gave up on ARN very soon after joining. There's so much verbiage and so little actually being said that it just gets frustrating. They're getting like the YECs - don't confuse me with facts, I know how I feel, and that's more important than mere facts. Plus all the levels of deception - it isn't really the Christian God, methodological naturalism and philosophical naturalism are just aspects of the same worldview, we don't really have an agenda for the renewal of society, we're just concerned about sciece (but don't confuse us with facts) and we don't really care about public opinon (except that that's our only focus these days) - are really tiresome.

Nic Tamzek · 07-30-2003, 05:46 PM

:banghead:

Nelson, in arguing against the idea that the first receptor with RAG could have been generic, writes:

Quote:

It depends on what the new variation binds to. First, due to the fact that generic binders bind many different antigenic structures in the first place, it is unlikely that it would bind to something it has never seen before, and probably won't persist.

But when I asked him if he thought the rearranging antibodies in sharks were specific or general:

Quote:

[Nelson, please say] whether or not shark re-arranging antibodies are general or specific.

Nelson replied:

Quote:

General. The shark immune system rearranges quite differently from the mammalian system.

:banghead: :banghead: :banghead: :banghead: :banghead: :banghead: :banghead: :banghead:

rafe gutman · 07-31-2003, 01:43 AM

quick question. nelson made the following comment:

Quote:

There is data that inconsistent the view that a transposase inserted itself into a primitive an innate receptor

In this review:

Quote:

Early on, it was suggested that the V(D)J recombination system might have arisen by the fortuitous integration of a transposable element into an ancestral antigen-receptor gene...Importantly, analysis of the unrearranged NS4 genes failed to detect the target site duplications that are hallmarks of transposon insertions. Thus, while the pre-rearranged NS4 genes appear to have been derived from unrearranged genes by germline V(D)J recombination, there is as yet no evidence to support the hypothesis that the unrearranged genes were derived from the pre-rearranged genes by insertion of a transposable element; this is discussed in a recent review by Lewis and Wu [16].

The review itself points out some evidence that the VDJ recombinase may be involved in already site-specific activity in the germ-line of the most primitive organism with acquired immunity.

(emphasis mine)

then later:

Quote:

Also there is no evidence (AFAIK) that a transposon inserted itself into an innate receptor so I don't see the relevance of the question.

i'm just curious if anyone here thinks nelson has a good point. i mean, he directly quotes a real research article saying "there is as yet no evidence to support the hypothesis that the unrearranged genes were derived from the pre-rearranged genes by insertion of a transposable element". if you guys weren't already suspicious of nelson's tactics, would you think that maybe there wasn't as much evidence supporting a RAG transposase model as i, or others, were making it seem?

hint: it looks like the original article is freely available online.

Nic Tamzek · 07-31-2003, 11:37 AM

Dude, I was just about to post on exactly this, because I couldn't stand it anymore, and here rafe has already gone and done it.

The original paragraph from Roth 2000 that Nelson quoted makes the context clear:

Quote:

How did these pre-rearranged genes arise? One possibility is that they are descendants of the ancestral antigen-receptor gene, before integration of the putative transposable element. A second possibility is that these genes arose from RAG-mediated DNA rearrangement events that occurred in the germline, an operation that violates the precept that the RAG recombinase is functional only in developing lymphocytes. A recent paper by Lee et al. [4] addresses these questions by examining immunoglobulin genes in the nurse shark. The nurse shark NS4 immunoglobulin light chain gene family provided very useful information, as there are several highly homologous genes present both in pre-rearranged and unrearranged forms. These features allowed the authors to evaluate sequences in sufficient detail to ascertain whether the genes bear characteristic features of V(D)J recombination or footprints of transposition. Their analysis revealed that the pre-rearranged genes did indeed contain tell-tale signs of coding joints formed by V(D)J recombination, including both N nucleotides and P nucleotides, which strongly suggest a hairpin intermediate. The presence of these features in several junctions suggests several independent germline V(D)J recombination events, although analysis of multiple unrelated individuals suggests that these events are not frequent. Importantly, analysis of the unrearranged NS4 genes failed to detect the target site duplications that are hallmarks of transposon insertions. Thus, while the pre-rearranged NS4 genes appear to have been derived from unrearranged genes by germline V(D)J recombination, there is as yet no evidence to support the hypothesis that the unrearranged genes were derived from the pre-rearranged genes by insertion of a transposable element; this is discussed in a recent review by Lewis and Wu [16].

So:

(1) In this paragraph, Roth is talking about the origin of the pre-rearranged receptor genes found sometimes in sharks, where the rearrangements are "hard-coded" into the germline.

(2) Roth says that the evidence favors the idea that these pre-rearranged genes are derived from V(D)J recombining genes via the normal action of RAG (normal except that it occurred in the germline cells)

(3) In the last bolded section, Roth is discussing an possible alternative hypothesis that says that the opposite occurred: that the unrearranged V(D)J genes were derived from pre-rearranged VDJ genes by *insertion* of RAG.

(4) We can be sure that this is what Roth meant by clicking on the handy link to reference 16, Lewis and Wu 2000, which says:

Quote:

In this issue, a study by Lee et al. (12) further investigates whether joined genes�later interrupted by a transposon insertion�or unjoined genes�subsequently connected by site-specific recombination�came first in the evolution of the Ig light chain locus in the nurse shark. There is increased interest in this issue, not only because it reveals the ways in which RAG-mediated events have reorganized Ig and TCR loci, but also because RAG-mediated transposition, though demonstrated in a purified in vitro system, has not yet been observed in any in vivo setting.

Lee et al. took advantage of the fact that certain Ig light chain genes in two shark species were apparent orthologs. Whereas all of the type III L chain genes in the horned shark were unjoined, the corresponding NS4 genes in the nurse shark occurred in both joined and unjoined form. A key feature of the analysis was that the NS4 genes in the nurse shark were highly homologous to one another, allowing evolutionary relationships to be established with some confidence. In combination, these circumstances enabled the authors to do two things: construct a phylogenetic tree of the NS4 family sequences, and provide through DNA sequence analysis a means to distinguish between the transposon integration and site-specific recombination scenarios.

As mentioned above, a sequence that has been interrupted by RAG-mediated transposition is expected to exhibit (relative to the uninterrupted form) a 5-bp target site duplication (or more rarely a 4- or 3-bp duplication; Fig 1 B, wavy lines) on either side of an RSS-bordered insertion (6) (7). A gene that has instead been joined through site-specific recombination is expected to exhibit (relative to the unjoined form) a loss of a small, unfixed number of bp from the ends of the joined coding sequences, along with the acquisition of junctional insertions (of two classes: one random in sequence, and termed an N insertion, another occurring only at ends that escaped trimming, and bearing a palindromic relationship to the cut end, termed a P insert; for a review, see reference 10). The two approaches taken by Lee et al. (12) returned the same answer: the joined NS4 genes arose through site-specific V(D)J recombination and not through germline RAG-mediated transposition. Their phylogenetic analyses indicated that germline joining occurred more than once, and in every case the unjoined form lacked any evidence of the DNA sequence duplications predicted for transposition. Instead joined genes exhibited junctions that appeared to reflect processing accompanying V(D)J recombination: trimming and P nucleotide addition.

In short, the germline "pre-rearranged" receptors of sharks (only some of the shark receptors are pre-rearranged) are derived from more typical V(D)J genes, and are not the ancestors of V(D)J genes. This was determined via phylogenetic analysis by Lee et al.

(5) Returning to the issue of the origin of V(D)J-RAG system, that both Roth (2000) and Lewis and Wu (2000) are supporters of the standard transposition-insertion-in-a-preexisting-nonrearranging-receptor hypothesis is shown by quotes from the respective papers:

Quote:

[Roth 2000]
Early on, it was suggested that the V(D)J recombination system might have arisen by the fortuitous integration of a transposable element into an ancestral antigen-receptor gene [14]. This hypothesis was strengthened by the discovery that the RAG genes are tightly linked [7], and by the finding that the RAG proteins can act as a transposase. Thus, a plausible model for the acquisition of the V(D)J recombination system during vertebrate evolution is the integration of a transposable element carrying the linked RAG genes into a primordial antigen-receptor gene in an ancestral jawed vertebrate, approximately 450 million years ago (reviewed in [1,11]). Presumably, this initial integration event created the first rearranging antigen-receptor gene; subsequent gene duplication events then created the multiple immunoglobulin and T-cell receptor loci.

Quote:

[Lewis and Wu 2000]

As recently as only a few years ago, any real information bearing on the actual genesis of the V(D)J recombination system seemed to be irretrievably lost. However, as more was learned about the molecular genetic and biochemical properties of the V(D)J recombination proteins, termed recombination activating gene (RAG)-1 and RAG-2, tantalizing suggestions of a transposon origin began to emerge. These clues included the following: first, the fact that the genes encoding RAG-1 and RAG-2, which are unrelated in sequence, are tightly linked, and as such share this property with genes that are known to undergo horizontal transfer (4). Second, the chemical mechanism of the recombination reaction, where DNA strand breakage and rejoining is accomplished through one step transesterification reactions, was like that of several well-described mobile elements (5). Finally, a surprising finding further indicated that RAG-1 and RAG-2 might have once been part of a transposon when two groups independently demonstrated that purified RAG-1 and RAG-2 proteins have a latent ability to carry out the transposition of DNA (6) (7).

Why this latter observation was so important is that there was no a priori expectation that a protein that can perform V(D)J recombination through site-specific recognition of recombination signal sequences (RSS) should also be able to transpose RSS-terminated DNA fragments. A quick description of both types of rearrangement is needed to appreciate this point, and will also come to bear later in this commentary. As diagrammed in Fig 1, the transpositional excision and reintegration of DNA (Fig 1 B) is a fairly different transaction from the creation of site-specific connections in V(D)J recombination (Fig 1 A). One difference is in the number and specificity of double strand DNA breaks; transposition not only entails the introduction of breaks at each of two RSS, as in V(D)J recombination, but also requires the generation of a third, non�sequence-specific cut at an undetermined integration site. The signature features of a transposition product versus those arising from site-specific V(D)J recombination are also quite distinct. After transposition, a transposed DNA fragment terminated by the RSS, is flanked by a five-nucleotide repeat created by a staggered cut at the target integration site ((6) (7); Fig 1 B, wavy lines). In contrast, after V(D)J recombination, a signal joint and a coding joint are created. Signal joints are formed from exact RSS fusions, and coding joints from fusions of the associated coding segments. The latter characteristically contain small, irregular nucleotide deletions and insertions, reflecting various processing operations performed on the coding end intermediates as they undergo joining (Fig 1 A). Thus, the unusual in vitro ability of RAG-1 and RAG-2 to do two quite different things, and in particular to transpose DNA, provided strong support for the original speculation that the V(D)J recombination system used to be a transposable element (3). The fact that the once portable genome now serves a different and highly utilitarian role in its new context suggests that the V(D)J recombination system stands as a prime example of the rehabilitation of "selfish DNA" (for a review, see reference (8)).

[...]

Figure 2. Postulated intermediates in the molecular evolution of the Ig and TCR loci. (A) One theory is that the event responsible for the existence of the modular recombination units characterizing today's Ig and TCR loci was a singularity that took place early in vertebrate evolution. With the integration of a mobile element, an ancient gene encoding an Ig superfamily domain was split into two parts. The mobile element imported RAG recombinase, its RSS, and possibly other element-related features, into the vertebrate genome. Reassembly of a functional exon required site-specific excision of the introduced mobile element, through a RAG-mediated recombination event targeting the RSS motifs. (B) After the RAG transposon integrated, the interrupted gene was duplicated. It has been suggested by Litman et al. (reference 2) that the presence of clustered arrays of duplicated genes, as found today in sharks, resembles an early locus configuration. On this view, V(D)J recombination activity in germline tissues could have led to the following derived features: (i) joined copies, as seen in cartilaginous fish, arose through a "standard" V(D)J joining event resulting in coding joint formation; (ii) the de novo creation of D segments could have arisen from intercluster recombinations resulting in the formation of signal joints with junctional insertions; (iii) the substitution of a 12-spacer RSS for a 23-spacer RSS or vice versa may have resulted from the "hybrid joint" outcome of germline joining. All of the postulated manipulations are RAG mediated and site specific. Events shown in i and iii are supported by evidence from sharks. MYA, million years ago.

(5) In his zeal to find something, anything, with which to object to Inlay's article and the devastating rebuttal to Behe's arguments it presents, Nelson is so blinded that he will blatantly misread articles (among his many other sins).

(6) jon_e hardly can tell his [bleep] from a tunicate when it comes to discussing the evolution of the immune system. He operates by free word association rather than actually understanding anything, and so he picked up on Nelson's quote containing the words 'no evidence' and ran with it because jon_e thought maybe Nelson had rafe stumped. This is just a subset of jon_e's main strategy of throwing out whatever ignorant objections occur to him over breakfast, and hoping that something sticks or at least is obscured enough in the pile of objections that rafe or mesk doesn't get around to educating him on the particular issue.

(7) Rafe is watching all of this with bemusement, and even egged them on a bit by asking them carefully if they really thought that Roth (an authority on the subject) supported what Nelson and jon_e were saying. Rafe is essentially giving them all the rope they need to hang themselves (again), not that it will have any impact at all with the blinkers they have on.

(8) When the above is revealed, Nelson and jon will continue on as if nothing had happened. Nelson will understand that he's been shown to be an ass but will deny that he meant what he said and begin obfuscating by changing the subject to other topics. jon_e won't even understand why Nelson was wrong, and will continue raising the "no evidence" objection as if it were established for the next three pages, until some other trivialities distract him (e.g., "Hey guys, I just read that skin is required for effective immune system function, this just reinforces my point that the immune system is IC!")

(9) None of them will ever get around to admitting that they've given away the store by failing to defend Dembski's and Behe's false assertions that the literature is silent on the evolution of IC systems.

I am of course just an amateur on this topic and might have misunderstood something about the shark receptor issue, but I think I've got the gist of it.

(rafe, reference/quote this post as you like (or not) over in the ARN thread. I admire your forbearance...I'm just using this thread as a fix to get off the ARN habit...)

KC · 07-31-2003, 01:34 PM

Rafe and Nic,

I've been trying to follow the discussion, but what struck me about Roth's article was he was talking about an event in nurse sharks that occurred only 7 million years ago, if I'm reading it right. So whatever the mechanism, Roth isn't talking about an event that had much of an effect on vertebrate immunological evolution.

Or am I missing something?

KC

Nic Tamzek · 07-31-2003, 04:03 PM

KC, yes, that's true AFAICT. The point of Roth's review was that germline rearrangments were late (at least the ones studied) relative to the origin of adaptive immunity.

The actual origin of adaptive immunity is only discussed in the beginning, where Roth gives the standard theory and the standard supporting evidence. OTOH, Lewis & Wu discuss the standard theory more.

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07-29-2003, 09:33 AM	#3
pangloss Veteran Member Join Date: Jun 2000 Posts: 1,302	Personally, I think Nelson has a learning disability....

07-29-2003, 12:40 PM	#5
Albion Veteran Member Join Date: Jul 2002 Location: US east coast. And www.theroyalforums.com Posts: 2,829	Sort of the opposite of irreducible complexity? Reducible coherence? I gave up on ARN very soon after joining. There's so much verbiage and so little actually being said that it just gets frustrating. They're getting like the YECs - don't confuse me with facts, I know how I feel, and that's more important than mere facts. Plus all the levels of deception - it isn't really the Christian God, methodological naturalism and philosophical naturalism are just aspects of the same worldview, we don't really have an agenda for the renewal of society, we're just concerned about sciece (but don't confuse us with facts) and we don't really care about public opinon (except that that's our only focus these days) - are really tiresome.

07-31-2003, 01:34 PM	#9
KC Senior Member Join Date: Mar 2002 Location: San Narcisco, RRR Posts: 527	Rafe and Nic, I've been trying to follow the discussion, but what struck me about Roth's article was he was talking about an event in nurse sharks that occurred only 7 million years ago, if I'm reading it right. So whatever the mechanism, Roth isn't talking about an event that had much of an effect on vertebrate immunological evolution. Or am I missing something? KC

07-31-2003, 04:03 PM	#10
Nic Tamzek Senior Member Join Date: Jan 2002 Location: California Posts: 646	KC, yes, that's true AFAICT. The point of Roth's review was that germline rearrangments were late (at least the ones studied) relative to the origin of adaptive immunity. The actual origin of adaptive immunity is only discussed in the beginning, where Roth gives the standard theory and the standard supporting evidence. OTOH, Lewis & Wu discuss the standard theory more.

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