******
Steve Clark probably didn't intend it, but he made a fair argument for why
the immune system must have been designed, rather than evolved:
>It is doubtful that any heritable mutation would be adequate to
>provide a mammalian defense system capable of adapting to
>newly arising pathogens. With their faster generation times,
>viruses et al. often stay one convenient step ahead of even the
>most adaptable component the immune system, which is the
>antigen receptor genes that undergo a high rate of somatic
>mutation when they encounter foreign antigen. However,
>this somatic mutation is not heritable.
******
My previous post speculated on a mechanism that would tune an *already
existent* immune system. It did not attempt to explain the origin of the
immune system or MHC genes. Rather, the mechanism modifies the sequence of
*existing* MHC genes. As proposed, the mechanism would operate on
populations (and species) over generations. (It would not fine-tune an
individual within it's own lifetime, the immune system already has other
mechanisms for that.)
Steve described the established view in this field. Take that view exactly,
and change one thing. In Steve's view, the gene conversion serves SOLELY to
inject *random mutation* into MHC genes. However, I speculate that the gene
conversion also injects a component of useful information. I also speculate
the information comes (in some way) from the result of viruses.
Gene conversion is capable of what I describe, so the issue is whether there
is information being injected, and (so far) Steve has not shown that
implausible.
His post made one central argument. He argued that my mechanism is
implausible because its RATE of adaptation would be too slow to do any good.
He didn't supply any numbers, and he needn't bother -- his argument fails
for a deeper reason. I never intended this mechanism to supply the
super-rapid immunity that develops within one individual's lifetime.
Compared with that, my mechanism provides a slower, less specific
trans-generational course correction for the MHC genes. Let me emphasize
again, my speculated mechanism is identical to Steve's view, with one key
difference. In Steve's view, the gene conversion injects *random* mutation
-- I speculate that it also injects information. Steve is ALREADY satisfied
with his view, therefore he cannot argue that the addition of information
makes the situation inadequate or too slow.
******
I think Steve misunderstood my idea. I will not fault him for that, rather
I take it as cause for more elaboration on my part. My idea is about
***information flow***, and my wording generalized the idea and stated it
broadly to emphasize that. Thus, my wording intentionally did not identify
the specific forms the information might take. Unfortunately, Steve assumed
the most unlikely form for that information.
Steve assumed I intended to create *entirely new* MHC genes out of virus
genomes. While my generalized discussion allows that interpretation, I did
not remotely limit it to that. In fact, I think that is by far the least
likely version of my idea. More likely is the possibility that fragments of
copies (or even imprecise facsimiles) of virus sequences end up as fractions
of the MHC genes. But even this was not the main thrust of my idea.
For example, the virus might directly turn an MHC gene into an MHC-like
pseudogene. That pseudogene contains some information about the virus. And
that information gets merged (by gene conversion) with the MHC genes, just
as Steve described. Thus, I see a potential information pathway.
The "information" I speak of is not necessarily the virus sequence itself.
The mechanism could work even without any virus sequences ending up in the
MHC genes. How? The virus preferentially attacks certain genes, and
creates pseudogenes. The very EXISTENCE of that PARTICULAR pseudogene,
signals the existence of the virus, and conveys information about its
identity. For example, hemoglobin pseudogenes may signal that hemoglobin
genes are under assault by viruses. In this way pseudogenes can convey real
information about particular viruses.
******
Here is another example. There are various MHC alleles. Imagine that (1) a
virus preferentially turns a specific one into an MHC-like pseudogene. The
virus has now fingered itself. The existence of the pseudogene (even
without virus sequences in it) signals information about the virus. This
pseudogene gets merged (by gene conversion) with other MHC alleles, pulling
them slightly in the direction of the originally attacked MHC allele. And
(2) the slight move in that direction improves the immune system response to
that virus or ones like it. In this way, the process could tweak MHC
alleles in response to viruses. I identified two key details in this
scenario that may be questioned. But this version of the idea is the
easiest for me to envision each step.
******
Information filter:
I saw the potential of information flow. Gene conversion might serve to
convey some information into the MHC genes and the immune system. But this
BY ITSELF is woefully inadequate. The organism is full of DNA "information"
and overwhelmed with it. There is too much DNA information, and it does no
good to send it all to the MHC genes. You need a filter -- an information
filter -- some way to preferentially filter INFORMATION ABOUT VIRUSES into
the immune system. I saw potential for such an information filter, and it
centered around pseudogenes.
1) Viruses create pseudogenes
2) MHC genes experience a gene conversion in which portions of other
*** MHC-like pseudogenes *** are exchanged with homologous regions
of expressed MHC genes.
3) Thus, pseudogenes can act like an information filter. Not all DNA
information is merged with the MHC genes -- only specific pseudogenes,
... and viruses create pseudogenes.
******
Information funnel and information use
Above I discussed two examples where the mechanism might be confined solely
to the MHC genes and MHC-like pseudogenes. On the other hand, it might
conceivably work for many varieties of pseudogenes throughout the genome.
If that is the case, then there are two additional information hurdles to
overcome:
1) The process would need an "information concentrator" or funnel, some
mechanism that takes information from various pseudogenes around the genome,
and funnels it into the MHC genes (or into the MHC-like pseudogenes). I
have not identified such an information funnel.
2) I have not identified how the immune system or MHC genes would actually
interpret and use information from various pseudogenes, such as from
hemoglobin pseudogenes. How would MHC genes use information from hemoglobin
pseudogenes? I have not identified how.
******
I thank Steve for his gracious comments on my admittedly speculative idea.
He didn't give it the flailing I anticipated would come. I emphasize again
that my idea is about information flow, and Steve has not even argued, much
less shown, that such information flow is implausible.
Walter ReMine
P.O. Box 28006
Saint Paul, MN 55128