New discovery of missing link between adaptive immune system and transposons

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As if Michael Behe wasn’t embarrassed enough, yet another paper has appeared in the literature providing more answers to the evolution of the adaptive immune system, one of his featured irreducibly complex (IC) systems in Darwin’s Black Box (see here and here for previous PT blogs on immune system evolution). In this new article, published in last week’s issue of Nature, the authors reported the discovery and biochemical characterization of a genetic element found in the common housefly, called Hermes, a member of the hAT superfamily of transposons. The significance? The mechanism of the transposition reaction is nearly identical to the reaction that generates antibody diversity in the adaptive immune system. This means that one component of the IC antibody generating system is found fully functional in an organism that lacks antibodies. That’s exactly the kind of thing that wouldn’t be predicted if IC systems were unevolvable.

Transposons are mobile genetic elements capable of ‘hopping’ from one location in the genome to another. They encode a transposase, which catalyzes the transposition reaction, by which a small piece of DNA (i.e. the transposon) is removed from the genome, and reinserted at a different location. While transposons are nothing new (our genome has more transposon DNA than protein-coding DNA), this particular transposon bears remarkable similarity to the process of recombination that occurs in antibody-producing cells to produce the diversity of antibodies essential to the adaptive immune system. In this process, called V(D)J recombination, gene segments are joined together by the removal of a small piece of DNA that separates them. The genes responsible for this reaction are called RAG1 and RAG2, which are acronyms for Recombination Activating Genes. As more was discovered about V(D)J recombination and the RAG genes, it became increasingly clear that the process evolved from a transposon. For example, the RAG genes are encoded by a single exon for each gene, and the two genes are grouped tightly together in the genome, similar to the organization of transposase genes within a transposon, but totally different than eukaryotic genes. Additionally, the recombination reaction bore some similarity to a transposition reaction, except that the DNA removed during recombination is not reinserted. Recently research has discovered that the RAG genes can catalyze full transposition reactions, both in vitro and in vivo. Despite these similarities, no transposase had been discovered that catalyzed transposition in the same manner as the RAG genes, and therefore any putative ancestor of the RAGs would look unlike any transposon that currently exists. That has now changed, with the biochemical characterization of hAT transposition. In addition to their similar biochemistry, Hermes and RAGs also share several structurally similarities, including a similar arrangement of amino acids in their active sites. A more detailed summary can be found here. In the original authors’ own words:

It had been suggested that the V(D)J recombination system may have evolved from an ancient transposable DNA element. Our findings here of such a close mechanistic relationship between hAT transposition and V(D)J recombination–that is, a double-strand break via hairpin formation on flanking DNA and 3’ OH joining to the target DNA–and the related active sites of hAT transposases and RAG1 provides strong support for the view that V(D)J recombination evolved from transposable elements.

What this means In his book, Darwin’s Black Box, Michael Behe identified V(D)J recombination as one of his IC systems, and proclaimed that it couldn’t have evolved. In his own words:

We can look high or we can look low, in books or in journals, but the result is the same. The scientific literature has no answers to the question of the origin of the immune system.

While there was already ample evidence before his book came out in 1996, and while there has been a deluge of research in the years since then (e.g. see my talkdesign article for review), this article adds yet another nail in the coffin of IC. Ever since scientists hypothesized the transposon origin of V(D)J recombination, several predictions were made that have since been confirmed. The discovery of transposase activity in RAG proteins, and now the identification of a transposition reaction nearly identical to the V(D)J recombination reaction, are but two. On the other hand, ID has offered no solutions to the origin of the immune system. IC systems were proclaimed by IDists to be a roadblock to evolution, since by definition the removal of one part of the system destroys its function. For the antibody generating system, they argued, what good are RAG proteins without antibody genes to recombine? Well, the housefly does not have antibody genes, but has proteins very similar to the RAGs.

Undoubtedly IDists will first ignore, then dismiss this evidence, all the while demanding “detailed, testable” calculations for the origin of the antibody generating system. In Darwin’s Black Box, Behe mentioned, then dismissed one paper that dealt with the transposon origin model:

They make a valiant stab at accounting for the components, but in the end, it is a hop in the box with Calvin and Hobbes. The authors speculate that a gene from a bacterium might have luckily been transferred to an animal. Luckily, the protein coded by the gene could itself rearrange genes; and luckily, in the animal’s DNA there were signals that were near antibody genes; and so on. In the final analysis the authors identify key problems with gradualistic evolution of the immune system, but their proffered solutions are really just a disguised shrug of their shoulders. (emphasis added)

A test of a model is the test of the predictions that stem from that model. Clearly the transposon origin model predicted that a transposon existed with features very similar to the extant RAG genes. The discovery of a transposon bearing those predicted features provides evidence of that model. One thing to note is that despite their similarity, RAGs and hermes are not homologues. Therefore, the next test of the model is to find a transposase that is truly homologous to the RAG genes. While it is always dangerous to make a prediction of what will be found (after all, the RAG homologue may have been lost in the subsequent 500 million years), the discovery of a RAG homologue would all but close the deal. The challenge for IDists is to explain the striking similarity between hAT transposition and V(D)J recombination, which are functionally very different reactions. I’m certain we’ll hear the “common design, common designer” explanation, but what predictions stem from that model? What details and tests can be derived? Here is where the IDist is stumped, and here is where you’ll hear the evasions, “What would you consider to be evidence for ID?” or “One prediction is that no IC system will ever be shown to have evolved”, or my favorite, “I believe your questions were already addressed here.”

29 Comments

Nice post. I’ve added this post to the EvoWiki immune system page.

This means that one component of the IC antibody generating system is found fully functional in an organism that lacks antibodies.

Haven’t all you’ve done is simply shown that the antibody system is IC? You have only one part of the system and of course no antibodies because all of the parts need to be present.

So, this is another one of these ‘similarity proves evolution’ arguments, heh? BFD!

J Low, what part of the posting did you not understand? The BFD is that evolution provides a logical explanation and more devastating ID does not.

Matt Inlay Wrote:

As if Michael Behe wasn’t embarrassed enough..

Michael Behe lacks the gene for the embarrassment response. ;-)

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Matt Wrote:

The mechanism of the transposition reaction is nearly identical to the reaction that generates antibody diversity in the adaptive immune system. This means that one component of the IC antibody generating system is found fully functional in an organism that lacks antibodies. That’s exactly the kind of thing that wouldn’t be predicted if IC systems were unevolvable.

I think that’s a bit of hyperbole. There are many similarities in both processes and structures across a wide variety of species of living organisms. Finding a process or mechanism in one system that is identical to a process or mechanism in another system means absolutely nothing of any evolutionary significance. Frankly, I’m surprised that a scientist of Dr. Craig’s stature would make such an audacious statement without any empirical evidence to support it. There are many mechanisms in plant cells that are identical to mechanisms in animal cells. Are we to deduce that animals are descended from plants?

Charlie Wagner

Charlie, when you do not understand something about evolutionary theory, do not blame the authors. Just ask. Your appeal to ignorance clearly shows how vacuous intelligent design really is.

Btw you may want to attribute your cut and paste to your ISCID ‘contribution’. Nevertheless your arguments are as unimpressive as usual.

Please educate yourself first Charlie…

Charlie,

In order to make a case against these kinds of papers, you have to go into the details. You can’t just continually repeat variations on “I don’t believe it” and expect to convince anyone.

Here is a summary diagram of the transposon model for the key step in the origin of adaptive immunity:

http://www.jem.org/content/vol191/i[…]00499.f2.gif

Based on these two (free I think) articles:

Susanna M. Lewis and Gillian E. Wu (2000). The Old and the Restless. The Journal of Experimental Medicine, 191(10), pp. 1631-1636.

Susan S. Lee, David Fitch, Martin F. Flajnik, and Ellen Hsu (2000). Rearrangement of Immunoglobulin Genes in Shark Germ Cells. The Journal of Experimental Medicine, 191(10), pp. 1637-1648.

A few of the problems with your arguments:

  • This model has had a number of predictive successes over the last two decades, according to a great many evolutionary immunologists, any one of them who probably knows more about evolutionary immunology than everyone on PT put together with the possible exception of Matt Inlay.
  • The processes involved in the model are mundane mutational processes (transposition, gene duplication, point mutation), with the good mutations retained by natural selection (which you always forget about). In this case, the selection is for increased receptor diversity, which other work shows is a very common requirement for dealing with diverse, rapidly evolving pathogens).
  • You have not explained why these processes are inadequate, and you have not given any attempt at a better model.

In short, Charlie, you’ve given no reason for anyone to believe you.

charlie wagner Wrote:

There are many mechanisms in plant cells that are identical to mechanisms in animal cells. Are we to deduce that animals are descended from plants?

Apparently, the concept of common descent has eluded you, Charlie. These identical mechanisms are attributed to a common ancestor for animals and plants, not a direct lineage.

The similarities between hAT transposition and V(D)J recombination are also attributed to a common ancestor. The authors are not saying that animals with adaptive immune systems descended from houseflies.

Charlie, scientists of Dr, Craig’s stature view the identical mechanisms in plant an animal cells as evidence of a common eukaryote ancestor. It’s the same deductions linguists use to determine how languages relate to each other. This raises an interesting question: Are there ID linguists that believe that languages don’t evolve? Do they feel that the evidence points to all languages being created in a single event by an unnamed Intelligent Designer that doesn’t want humans creating large towers?

Craig T Wrote:

Charlie, scientists of Dr, Craig’s stature view the identical mechanisms in plant an animal cells as evidence of a common eukaryote ancestor. It’s the same deductions linguists use to determine how languages relate to each other. This raises an interesting question: Are there ID linguists that believe that languages don’t evolve? Do they feel that the evidence points to all languages being created in a single event by an unnamed Intelligent Designer that doesn’t want humans creating large towers?

Sadly, Craig, the answer to that question is almost certainly ‘Yes’.

Charlie I know you have no idea how to connect the dots.

The issue was AI was supposed to be IC. That if you removed any one part the whole system would fail and there would be no benifit to the remaining parts.

What this shows is that parts of the AI system have benifits outside of the AI system. Thus these parts could, and did, evolve for their own functionality but later when other mutations occured the functionality changed.

What is your explanation? That your alians just haven’t finished the job of AI system in house flies. Kind of a half built deal?

replace “user” with “waynefrancis” to prevent spam

This raises an interesting question: Are there ID linguists that believe that languages don’t evolve? Do they feel that the evidence points to all languages being created in a single event by an unnamed Intelligent Designer that doesn’t want humans creating large towers?

On the Bathroom Wall I spell out exactly such an Intelligent Design Linguistic Theory. Maybe Charlie has an equally intelligent brother who can take up that cause, if he’s too busy with biology.

I understand people’s frustrations with antievolutionists, but I’d prefer this thread not devolve into creationist bashing.

Charlie, I appreciate your lengthy response, but the only section of your response relevant to this paper was:

While the authors are entitled to speculate on the possible implications of their findings with respect to evolutionary theory, I think it would be disingenuous to cite such a paper as support for the notion that “the gradual evolution of the “IC” immune system (is) a perfectly reasonable idea supported by a fair number of observations and peer-reviewed articles.”

You haven’t really addressed the evidence the authors presented. How would you explain the similarity between hAT transposition and RAG-mediated rearrangement? These processes have nothing to do with each other, one moves small genetic elements around in nearly all eukaryotes, the other generates fully functional antibody genes from gene segments in vertebrates. hAT transposition has nothing to do with immunity, RAGs are vitally important to the adaptive immune response. Is it just a coincidence that they share the same mechanism?

Hi J low, thanks for replying. You wrote:

Haven’t all you’ve done is simply shown that the antibody system is IC? You have only one part of the system and of course no antibodies because all of the parts need to be present.

If you’re referring to Behe’s original definition of IC, then the ICness of the antibody system was not in question. I agree completely with your second sentence. In Darwin’s Black Box, Behe lists three basic components to the antibody generating system, the RAG recombinase, the recombination signal sequences (the genetic sequences that serves as binding sites for RAGs), and lastly the antibody-encoding genetic sequences. He argues that any of these three components are useless without the others. However, the fact that an organism possesses proteins with similarity to the RAGs, but does not possess the antibody genes, indicates that RAG-like proteins are functional without the antibody genes. I should also note that transposons contain sequences very similar to recombination signal sequences (also called RSSs). What this means is that a system exists that contains 2 of the 3 parts of the antibody-generating system. This suggests that the 3 parts antibody-generating system could have evolved from the 2 part transposon system by the addition of a single part. The gradual accumulation of parts to form an IC system is clearly inconsistent with the idea that IC systems are unevolvable.

The existence of a transposon with a similar mechanism as RAG-mediated recombination is a prediction of the transposon-origin model. It’s not just a matter of similarity. The transposon-origin model makes specific predictions about what will be similar, and how similar it will be. The next prediction is that a homologue to the RAG genes will be found in an organism that does not possess the antibody generating system. I could even give you a % similarity that would be predicted, which would vary depending on the organism. If such a protein was found, and it had the predicted % similarity, would that help convince you?

Matt Wrote:

You haven’t really addressed the evidence the authors presented. How would you explain the similarity between hAT transposition and RAG-mediated rearrangement? These processes have nothing to do with each other, one moves small genetic elements around in nearly all eukaryotes, the other generates fully functional antibody genes from gene segments in vertebrates. hAT transposition has nothing to do with immunity, RAGs are vitally important to the adaptive immune response. Is it just a coincidence that they share the same mechanism?

The same genes, the same structures and the same processes turn up again and again, from one species to another across a broad spectrum of living organisms. We’re all made of the same fabric, we’re all part of the same web. And that is an observation of profound importance. All living things are related and probably had a common origin. For example, the gene for hemoglobin can be found in the bean plant (V. fava) despite the fact that bean plants do not make hemoglobin. What are we to make of this? It speaks clearly to the unity of all life, to the relatedness of all life. Dobzhansky got it wrong. He said “nothing in biology makes sense, except in the light of evolution”. What he should have more correctly said is “nothing makes sense in biology except in the light of relatedness.” Unity of structure, process and function is the defining principle of biology. Unfortunately, many people conflate this unity of structure and process with evolution. I have never argued that evolution did not occur, only that it did not occur without the benefit of intelligent guidance. These papers that have been mentioned only underline this unity of structure and process and underscore the fact that all life is related. They say nothing at all about the mechanism of this evolution, whether it was the result of random processes, as darwinists claim, or the result of intelligent input, as I claim.

You can’t just continually repeat variations on “I don’t believe it” and expect to convince anyone.

“…outside the ID community,” you mean.

Charlie, thanks for replying. You wrote:

The same genes, the same structures and the same processes turn up again and again, from one species to another across a broad spectrum of living organisms. We’re all made of the same fabric, we’re all part of the same web. And that is an observation of profound importance. All living things are related and probably had a common origin.

There’s nothing I disagree with in this statement.

Unity of structure, process and function is the defining principle of biology.

I disagree. Those are just observations. The question is why is there unity of structure, process and function?

I have never argued that evolution did not occur, only that it did not occur without the benefit of intelligent guidance. These papers that have been mentioned only underline this unity of structure and process and underscore the fact that all life is related. They say nothing at all about the mechanism of this evolution, whether it was the result of random processes, as darwinists claim, or the result of intelligent input, as I claim.

How do you determine whether intelligent guidance occurred in the evolution of life? The problem with intelligent design is that it requires that natural evolution did not occcur. The only evidence for ID is evidence against evolution. ID has no mechanism. Without a mechanism, there’s no basis to make predictions. If you disagree, then tell me, what is the mechanism of ID? What predictions stem from it? The fact that no one is even trying to answer these questions speaks volumes.

It’s not just the fact that genes are similar, it’s how they are similar and to what degree they are similar that provides evidence for common ancestry. But it seems you agree with this. Is your interpretation different from theistic evolution? They basically sound the same.

Charlie writes,

For example, the gene for hemoglobin can be found in the bean plant (V. fava) despite the fact that bean plants do not make hemoglobin. What are we to make of this? It speaks clearly to the unity of all life, to the relatedness of all life.

It’s highly misleading to say this. I did a bit of digging, you are referring to leghemoglobin in beans, which is indeed homologous to mammal hemoglobin, but only very distantly (as part of the ubiquitous globin family of proteins):

Lehtovaara P, Ellfolk N. (1975). “The amino-acid sequence of leghemoglobin component a from “Phaseolus vulgaris” (kidney bean).” “Eur J Biochem.” 54(2):577-84.

Abstract: 1. Leghemoglobin component a from Phaseolus vulgaris (kidney bean) was digested with trypsin; 15 tryptic peptides and free lysine were purified and the amino acid sequences of the peptides determined. 2. The internal order of the tryptic peptides was determined by the bridge peptides obtained from the thermolytic digest and the dilute acid hydrolyzate of kidney bean leghemoglobin a; 12 thermolytic peptides and two acid hydrolysis peptides were purified and the sequences were partially or completely determined. 3. The complete amino acid sequence of kidney bean leghemoglobin a is compared to that of leghemoglobin a from soybean (Glycine max) and to some animal globins. As regards sequence, the kidney bean globin has 79% identity with the soybean globin and 21% identity with human hemoglobin gamma-chain. Seven of the 14 amino acid residues common to most globins are found in the kidney bean globin. Trp-15 and Tyr-145 are evolutionarily conserved in this globin, which confirms the concept of a common origin of animal and plant globins.

((bold added))

Craig T says “Are there ID linguists that believe that languages don’t evolve?”

No.

Are there evolutionists who believe that language is the result of random interactions between non-living chemicals?

Dave still seems to be confused about evolution…

DaveScot Wrote:

Craig T says “Are there ID linguists that believe that languages don’t evolve?”

No.

Here is an example of a creationist asserting that separate languages were intelligently designed:

http://www.answersingenesis.org/cre[…]g_change.asp

Adam - Dr. Wieland is not a linguist. He’s a medical doctor. He only meets half the qualifications for an “ID linguist”.

Matt Wrote:

I disagree. Those are just observations. The question is why is there unity of structure, process and function?

Because all living things probably had a common origin. The same mechanisms, the same processes probably gave rise to all life forms. Unfortunately, we don’t have a clue what those mechanisms and processes are or whether they are random, accidental processes, the result of some yet to be discovered first principle, intelligent design or the hand of God.

Matt Wrote:

How do you determine whether intelligent guidance occurred in the evolution of life?

By using the scientific method. I laid all of this out in my recent paper: http://www.charliewagner.net/casefor.htm Simply put, there are no examples in the natural world, insofar as we can determine, in which random processes gave rise to highly organized systems. There are none at all. Now science never really “proves” anything, it only determines what is “most likely”. It would seem to me that, absent even one falsifying example, it would be a pretty good bet that living things are the result of intelligent input.

Matt Wrote:

The problem with intelligent design is that it requires that natural evolution did not occcur.

It does not. It only requires intelligent input, which does not have to be supernatural. Can you not imagine an entity that is as far above us as we are above bacteria?

Matt Wrote:

The only evidence for ID is evidence against evolution.

No again. This is not an argument against evolution, it’s an argument for intelligent input in that evolution.

Matt Wrote:

ID has no mechanism. Without a mechanism, there’s no basis to make predictions.

The mechanism of evolution is not presently known. So we’re all in the same boat. Evolution by intelligent input is just as likely (more likely in my opinion) than evolution by random, accidental processes.

Matt Wrote:

If you disagree, then tell me, what is the mechanism of ID? What predictions stem from it? The fact that no one is even trying to answer these questions speaks volumes.

There is no mechanism of ID at the present time, but it is disingenuous to say that no one is even trying to answer these questions. Every day, in hundreds of laboratories across the world, research is being done into the functions and processes of the genome, in molecular biology and molecular genetics. That’s where the answers lie, in the genome. And every day, new discoveries are being made that make darwinian evolution less likely and intelligent design more likely.

Charlie Wagner http://enigma.charliewagner.com

Charlie Wagner Wrote:

For example, the gene for hemoglobin can be found in the bean plant (V. fava) despite the fact that bean plants do not make hemoglobin. What are we to make of this? It speaks clearly to the unity of all life, to the relatedness of all life.

To expand on what Nick said, leghemoglobin is used to sequester oxygen in the root nodules of legumes. These nodules contain anerobic nitrogen-fixing bacteria that require an oxygen-free environment. So leghemoglobin in legumes serves a similar, but distinct function from hemoglobin in animals. Clearly they share a common ancestor in the distant past, but as Nick said, globins are ubiquitous, so there is nothing strange about plants and animals having homologues in this case.

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Nice post, wah.

I can’t recall Charlie being presented with a better written version of your explanation.

Will Charlie Wagner finally realize the vapidity of his bogus arguments from incredulity? Will he finally stop citing the work of evolutionary biologists as evidence that alien beings created all the life forms that ever lived (and died) on earth?

Tune in for the next unsurprising installment when Charlie asks, “Where are the transitional fossils?”

DaveScot categorically, with Confident Authority Wrote:

Craig T says “Are there ID linguists that believe that languages don’t evolve?”

No.

http://www.icr.org/creationscientists/oller.html All members of the ICR must take the Young Earth (incl. Tower of Babel) oath of fealty. Should the Authoritative Mr. Scot now concede Oller is a highly credentialled linguist but is not an Offical IDer, it should be pointed out Oller authored a chapter in the (2nd or 3rd) flagship book of the ID movement. The Creation Hypothesis: Scientific Evidence for an Intelligent Designer, 1994, in which Dembski, Meyer, make their first appearance, allong with YEC’s Wise, Weldon, Moreland(cagey on his YECism?) etc. Now if only one had the time to educate Scot on his more serious categorical misstatements about biology. But 20 patents and stock anti-pointyhead-elitist rightwing politics tend to give one Confident Authority.

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This page contains a single entry by Matt Inlay published on January 8, 2005 2:29 PM.

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