Evolution of the immune system

Mon Dec 7 14:31:32 EST 1992

Larry wrote (ref.3)

>Don Forsdyke asks,(ref.2)
>     "But Larry, is it not true that certain evolutionary developments
>      virtually arrest certain species in a frozen state so that other
>      avenues of evolution are closed off for them. Once the giraffe
>      had decided to go the route of elongating its neck it rapidly
>      reached perfection regarding its particular ecological nitch.
>      Necks evolved long before the giraffe, but if one wanted to study
>      the properties of necks, the giraffe, rather than Homo sapiens
>      would seem an ideal example."
>I'm not sure that I understand Don's point here.

       It is not a particularly profound one. Just that certain features of
living organisms get "frozen", so that studying them in modern organisms is
like studying living fossils. Example: Once the "decision" to begin life based
on L-amino acids was taken, all life forms on earth followed that path. The
L-amino acids we see in modern organism are the evolutionary "echo" of that
primeval decision. Another example: Crick, I believe, pointed out that once the
genetic code was settled, that was it. Apart from the occasional exception, we
all use the same code. So the modern genetic code would seem to be a valid
echo of that distant decision.
>                                                                       I don't
>think that it is helpful to think of any species as being in a "frozen state".
>Don, did you mean this as an argument in favour of "living fossils"?

        Yes, for the reasons given above.
>I mentioned that 'phage and viruses have sophisticated defense mechanisms
>that were probably not evolutionarily related to those of mammals. This
>prompted the following from Don Forsdyke:
>     "I presume here you are talking about interactions of viruses with
>      their hosts. These are largely intracellular (e.g. the evolution of
>      restriction enzymes by bacteria and anti-restriction enzymes by
>      phage). Now, are you saying that the immune systems of mammals do
>      not have an intracellular component? What is all this business about
>      intracellular processing of protein antigens and peptide presentation
>      in association with MHC class I? Can we learn anything from the great
>      facility of bacteria to form inclusion bodies of expressed FOREIGN
>      proteins? I think you go too far in saying it is "unlikely" that this
>      is evolutionarily unrelated to mammalian intracellular immune
>      mechanisms."
>Actually I was thinking about tail fiber genes and the fact that they have
>a constant region and a variable region that is involved in interactions
>with the bacterial receptor. Some 'phage have a number of variable regions
>that can be attached to the constant region by recombination. This gives
>rise to different tail fibers that alter host range specificity. The genes
>for bacterial receptors also show considerable variation in different strains;
>this is presumably a result of selection for 'phage resistance. Restriction
>and modification are other examples of bacterial defense mechanisms.
>I stand by my statement that these mechanisms are not evolutionarily related
>to those of the mammalian immune system. This does not mean that the
>bacteriologists can't profit from the knowledge gained through immunology
>and vice versa. Different organisms may use similar strategies and mechanisms
>that are not necessarily related by evolution. Comparative studies are very
>profitable because they broaden one's horizons and stimulate thinking in
>new directions. We lose this advantage if we try to interpret everything in
>terms of its relevance to mammalian immunology or if we believe that the
>mammalian systems are the most "advanced" and everything else is primitive.
>Finally, Don closes with;
>     "Well, Larry, what about the heat-shock proteins. Highly conserved
>      and guess where some of them map on mammalian chromosomes...the
>      MHC complex!"
>These genes are the most highly conserved genes known in all of biology and
>this reflects their fundamental importance as chaperones that catalyze the
>folding of proteins and their assembly into macromolecular structures. It
>is not surprising that MHC class I and class II molecules might use chaperones
>such as hsc70 and BiP since evolution of this system in vertebrates is a
>relatively recent event while the functions of the chaperones have been
>honed over millions of years. (Other chaperones are also important.)
>The genes found in the MHC locus of mammals are the inducible genes that have
>nothing to do with the immune system as far as we know. There are dozens of
>genes in this region that do not play a role in antigen presentation. The
>important genes are hsc70 and BiP and they map elsewhere.
>Speculations in the literature that there is an evolutionary relationship
>between HSP70 genes and class I genes are not supportd by the data on
>alignments - there is no such relationship. Attempts to force a class I
>structure on the C-terminus of HSP70's by making predictions of secondary
>structure are also without value. I don't know where class I and class II
>molecules came from but they certainly didn't evolve from an HSP70 gene.
>Don, I realize that I may be overreacting to your comment. Can you explain
>why you think that it is significant that some of the stress inducible
>members of the HSP70 family map to the class III region along with many
>other genes that are not functionally related to histocompatibility?
      Genes which have arisen separately, and therefore demonstrate no
sequence similarities, may become closely linked because they are functionally
related. Two genes which map in, or close to, the MHC complex are:    an HSP70
gene and TCP-1 gene (encoding a chaperonin). There is growing evidence that
these are involved in immune processes (I can get the references for you).
Precisely what this role is, is a matter of speculation. A gopher ride to
the University of Michigan Biology Archive, and examination of the Bionet.
Immunology discussions for August 1992, provides a debate on this topic.

                    Sincerely, Don Forsdyke

Refs: Moran, L.A. (1992) Bionet.immunology 1203, 1319gmt
      Forsdyke, D.R. (1992) Bionet.immunology 1203, 1333edt
      Moran, L.A. (1992) Bionet.immunology 1204 2018gmt

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