New discovery of missing link between adaptive immune system and transposons
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.”