Evolution of Adaptive Immunity IV–”Lawful”* accidents of heredity visible in adaptive immunity

I should add at the outset that it may not be merely accidents of heredity (along with the many other factors) that are so visibly behind adaptive immunity, but that horizontal transfer may play an important role as well, even if heredity is responsible after the putative horizontal transfer.

Certainly many of the accidents of heredity have been mentioned previously in my discussions of this subject, from Toll-like receptors ultimately triggering adaptive immunity, to the considerable evolution of the molecular families involved in “innate immunity” and “adaptive immunity” since adaptive immunity arose, mentioned here. However, mostly that evolutionary evidence is not specific to adaptive immunity, and even though I am totally unwilling to pretend that the integrated “adaptive” and “innate” functions are separately evolving systems, it is important that adaptive immunity, as separately conceived, should be evolutionarily understood as far as possible. And, fortunately, quite a lot regarding its evolution is known, while conjectures filling some of the gaps also have supporting evidence behind them.

I would just note that in this post I am primarily discussing the evolution of adaptive immunity in gnathostomes (jawed vertebrates), and not the separately evolved (and basically unrelated) adaptive immunity of agnathans (hagfish and lampreys).   Yet for understanding gnathostome immune system evolution in context, the evolutionarily-derived similarities are important for showing what existed prior to the evolution of gnathostome and agnathan immune systems.  Here is a passage highly revealing of the “physical precursors” (Behe rightly insists that “physical precursors” are essential for “Darwinian evolution” in DBB, but fails to mention that these are generally found) to adaptive immunity:

Cells with phagocytic and other innate-immune-defense capabilities are present in many invertebrate species, but none of them have been shown to be long-lived migratory cells with clonally diverse anticipatory receptors and adaptive-immune-response capabilities. On the other hand, cells with the characteristic morphological features of lymphocytes and much of the molecular machinery possessed by gnathostome lymphocytes have been found in lampreys and hagfish (Uinuk-Ool et al., 2002, Mayer et al., 2002, Najakshin et al., 1999 and Nagata et al., 2002), the only two living agnathan representatives. These findings suggest that lymphocyte progenitors evolved in the most basal vertebrates, or possibly a protochordate ancestor.

Many of the genes for transcription factors involved in gnathostome lymphocyte development can be found in agnathans. SPI-B, IKAROS, EBF, GATA, PAX-2/5/8, and BACH2 gene relatives have all been identified in the lamprey (Rothenberg and Pant, 2004). Since many of the signaling pathways involved in inflammatory responses, such as the NF-κB pathway, exist in insects, it is not surprising that lymphocyte-like cells in lampreys possess NF-κB and STAT signaling-cascade components. Many additional genes that our lymphocytes use for activation purposes are expressed by lamprey lymphocytes (Mayer et al., 2002 and Pancer et al., 2004b). These include genes for the CD45 transmembrane protein tyrosine phosphatase, SYK protein tyrosine kinase, Src family members, and the HS-1 adaptor molecule. Lamprey lymphocyte-like cells also express relatives of the CXCR4 chemokine receptor and its SDF-1 ligand, the cytokine interleukin 8 (IL-8) and its receptor, and the IL-17 receptor. In keeping with their apparent lack of MHC genes, agnathans possess only the preduplication genes for each of the three proteasome subunit pairs needed for gnathostome immunoproteasomes to produce peptides that fit into the cleft of MHC class I molecules (Klein and Nikolaidis, 2005). The identification of this constellation of cellular components in lampreys suggested that, given the ability to make diverse anticipatory receptors, agnathan lymphocyte-like cells are potentially capable of mediating adaptive immune responses.  The Evolution of Adaptive Immunity

The linked source above is quite a good relatively brief source for understanding the evolution of both systems of adaptive immunity.

Especially interesting is the situation that the crucial lymphocytes would appear to have evolved well before adaptive immunity did, and that even those apparently have counterparts in invertebrates today, but without the long-lived migratory ability of lymphocytes.  There is, of course, the possibility (though I cannot think it all likely) that either of the two adaptive vertebrate immune systems evolved independently after the earlier one already existed, but, even then, leukocytes would have already existed for at least one of the systems.

At the heart of gnathostome adaptive immunity, however, is the recombination of the V(D)J gene segments of immunoglobulins by prototypic T and B lymphocytes, which is initiated by RAG1 and RAG2.  The V(D)J gene segments are found in the TCR and BCR genes, and provide the components for T antibodies and B antibodies respectively.  This description is terribly abbreviated, but links provide the necessary background information, while I only mention these facts in order to point out why TCR, BCR and RAG1and RAG2 are considered for phylogenetic studies, along with MHC class I and class II genes.

The excerpt above notes that agnathans evidently lack the MHC genes.  Yet MHCs use the Ig domains of the Immunoglobulin superfamily (IgSF), so have a broad ancestral linkage in that way, as do the BCR and TCR genes.  IgSF proteins are found in insects, and some of these may have immune functions (The Evolution of Adaptive Immunity). 

More interesting from the standpoint of observing a rather exact record of the evolution of adaptive immunity is the fact that agnathans have one TCR-like gene and a VpreB-like gene (one of the “surrogate light chains” of BCR), despite the lack of agnathan use of these genes for their own adaptive immune systems.  In addition, the TCR-like gene actually has the V- and J-like sequences used in gnathostomes, only these are within “a single V region exon,” so would not operate in proper gnathostome fashion (The Evolution of Adaptive Immunity).

 It is stunning from any “design” sense to see our relatives, the agnathans, with genes that could almost effect the actions of our adaptive immunity.  It is essential to, and predictive of, evolution that genes able to be modified through relatively slight changes exist in ancestors prior to the existence of adaptive immunity, and hagfishes and lampreys preserve the record of at least some of these necessary genes.  This is in addition to the previously-established fact that adaptive immunity comes from, and is integrated into, innate immunity, which would be necessary for the evolution of such a complex biochemical pathway.

There is more, however.  The core of RAG1 has also been found to have a homologs in animals which have diverged from our own common ancestor.  These homologs are Transib transposases, whose functions are to break DNA up in order to insert transposons into the genome.  Because RAG1 and RAG2 perform very similar actions as the transposases in order to rearrange the V(D)J segments, it was hypothesized that their genes would derive from transposase genes.  There are “RAG1 Core–Like Sequences in the Sea Urchin, Lancelet, Starlet Sea Anemone, and Hydra Genomes,” as my source indicates.  The homolog in the lancelet is presumably the most important relationship to our adaptive immune system, since the lancelet is a chordate, as are the vertebrates.  See RAG1 Core and V(D)J Recombination Signal Sequences Were Derived from Transib Transposons.

Unfortunately for Behe, his little consideration of the actual science of the evolution of adaptive immunity includes this gem:

…It’s on thing to say an organism has a completed, functioning system, and another to say how the system developed.  The authors certianly realize this.  They note that

immunoglobulin and TCR genes both require RAG proteins for rearrangement.  On the other hand, RAG proteins require specific recombination signals to rearrange immunoglobulin and TCR genes

(RAG is the component that rearranges the genes.)  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.  Darwin’s Black Box 137

Ah, yes, the attempt to fault evolution for actually accounting for what happened across the taxa.  It is, as I have stated, an accident of heredity that we ended up with the TCR and BCR genes which provide the gene segments which are then rearranged by RAG proteins, and of course it is also an accident of heredity that we ended up with a proper transposase core that could rearrange the V(D)J pieces.  But we account for the accidents in our theory, for evolution can only occur with relatively likely accidents. 

There is nothing particularly odd about transposases in a genome, TCR and BCR genes–that these, or their homologs, exist in organisms lacking adaptive immunity shows that to be the case.  The accidental nature of evolution is simply that those particular genes ended up in our ancestors, so again, the accident is in the particulars of heredity.  What would be strange is for a designer to go around seeding organisms that lack adaptive immunity with exactly the genes needed for their relatives to evolve heredity, even though they have no need for these particular genes, as opposed to genes with similar functions.

No, paradoxically, the ancestral transposase genes and the TCR and BCR genes were not accidentally within the vertebrate genome at all, that is, not in the sense that Behe claims that they were.  They were there because vertical genetic transfer dictates that the accidents of evolution will be substantially preserved (subject to evolutionary change, naturally) in the genome, and it will be these preserved elements that provide the basic resources for further evolutionary changes. 

To elucidate further, there are different kinds of accidents.  Science recognizes the endless production of accidents, within the constraints of “natural law”* and other known regularities.  These types of accidents are abundant throughout, and are conclusive evidence for, biological evolution.  The accidents of a TCR-like gene, and part of a BCR-like gene in agnathans, and the accident of the RAG1 core gene in our chordate ancestor, are the “lawful”* sorts of accidents that are unavoidable in evolution, hence are predicted by evolutionary theory.

What Behe wants us to believe is that the “lawful” acquisition, and causal transferral via heredity, of the accidents of our evolutionary ancestors are in fact accidents of the unexplainable, spooky (supernatural) kind.  While he certainly missed the mark on the RAG1 gene, his usual fallback position has been that homologous genes simply “indicate heredity,” and nothing else.  No, that’s missing the heart of evolutionary processes, for evolution is constrained by present and past accidents.  RAG1 is not at all a “lucky” occurrence (not at the inception of the evolution of adaptive immunity, that is), it is one of the few genes that unguided evolution could possibly use to evolve a crucial function of adaptive immunity, hence its evolutionary modification into immune functionality is “law-like”*–which sorts of actions traditional Catholics have credited to God.

In later writings (namely, EoE), Behe brought up the possibility of “design” by God choosing a universe out many that would produce the requisite mutations for a desired outcome.  This is too bizarre, however, because this is essentially a kind of multiverse concept used not to explain how the conditions of life came to be right, but one in which incredible accidents are selected by God to account for the entire course of evolution.  In other words, rather than crediting God for purpose (other than the one existing behind the chosen “possible universe”), rationality, and evident design, God is responsible for incredible and unlikely accidents, a sort of hyper-accident in the operation of the universe, yet a fine-tuning of the underlying laws of the universe.

In one way, then, he credits God for order and “lawfulness”, and in the other he credits God for extremes of accident, neither reconciling the two opposite notions, nor explaining why God didn’t opt for the malaria-free universe, or the one that gave us super-intelligence, radio communications, and the ability to fly (surely all of these are possible in an infinite number of evolutions of life).  The result is an incoherent God, let alone one lacking in benevolence.

Getting back to the core of this post–after that little excursion into the strange and irrational “saves” that Behe is forced to invoke–I wish to point out that not all of the genes of adaptive immunity have been found to have homologs in our agnathan, non-vertebrate chordate, or invertebrate relatives–notably the RAG2 gene .  Questions of how adaptive immunity evolved abound, certainly.  But unless we are willing to embrace the extremely unlikely accidents of Behe’s later “thought,” or the strange accidents that “designed” our relatives to retain evidence of a number of the needed precursors for “lawful” evolution, we will stick to the “lawful”* accidents which evolution must utilize in modifying life and its systems.  For it is an accident that we had the particular genes we did before we evolved adaptive immunity, yet it was not at all accidental that we would have the functions of TCR-like, BCR-like, and RAG1-like genes before  our particular type of adaptive immunity arose. 

Nature, and thus evolution, continue to operate according to “law-like” regularities, much as traditional theists have claimed.  Many theists did suppose that there was an early intervention, to produce life.  However, few considered pure accident or unknowable intervention to be at work through the course of earth’s history–for that would make our intelligence unable to reliably make sense of what we observe, quite like Behe’s claims fail to make sense out of observation.

We accept the accidents of evolution because they do not deviate from the processes that we observe, and because the same patterns in “microevolution” exist in “macroevolution.”  “Lawful accidents” are all that we ever propose to exist, and to explain the patterns of “microevolution” and of “macroevolution.”  Behe would have us believe that incomprehensible accident, or unknowable intervention (it is not sensible, knowable “complexity” that Behe claims to be the mark of design, quite unlike Paley’s contention), is responsible for the “law-like”* patterns discovered to underlie the appearance, and relatedness, of gnathostome innate immunity. 

Unfortunately for him, this means not only that science is worthless, but so is rational thought.  According to him, we are the result, and the observers, of the incomprehensible accident (at least from our unprivileged viewpoint) that this universe is said by Behe to be.  The problem for the IDists is that “design” itself no longer has any meaning in such a universe, and we can only be left in an existential nightmare of appearances without any kind of truth existing behind these.  As a matter of intellect, it becomes the worst possible world, for no observation of regularities (such as we find in “macroevolution”) is reliable in the IDist universe.

*I use quote marks around “lawful” and related words, because modern science and philosophy understand “nature’s laws” to be the result of inductive reliable observational regularities, and not as absolute and unquestionable verities such as one might credit to God.

This is part of a series of posts that I am combining into one long post, which may be found at Darwin’s Black Box.

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3 Comments on “Evolution of Adaptive Immunity IV–”Lawful”* accidents of heredity visible in adaptive immunity”

  1. [...] Behe Fails Weblog Just another WordPress.com weblog « Evolution of Adaptive Immunity IV–”Lawful”* accidents of heredity visible in adapt… [...]

  2. [...] via rational efficient causation).  Likewise, they totally avoid efficient causation, for as I previously argued, they have no causes at all, only unconstrained accident (or [...]

  3. [...] and Pleiotropy shows us that Development shapes evolution in silico. The Behe Fails Weblog presents Evolution of Adaptive Immunity IV–”Lawful”* accidents of heredity visible in adaptive immunity while For The Sake Of Science puts to rest an old Creationist trope with Why Natural Selection is [...]

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