The MHC genes of higher organisms have a "mutation rate" higher than normal.
That struck me as peculiar ever since I first heard it, since those genes
are involved in the immune system. I suspected that a high mutation rate,
ESPECIALLY FOR THESE GENES, allows species to rapidly develop an immunity to
new local pathogens. I do not think I have been alone in that suspicion. I
also find it wonderfully congenial to a creationist viewpoint.
Steve Clark said something that struck me as interesting:
>MHC loci display what Jan Klein once claimed to be the highest
>rate of GERMLINE mutation in the mammalian genome. This mutation occurs
>via a process called gene conversion in which portions of other MHC-like
>pseudogenes are exchanged with homologous regions of expressed MHC genes.
>This is a special type of mutational mechanism that does not seem to be used
>routinely by mammalians. However, it is more common in lower species like
>fungus.
And,
>The lesson from the MHC system is that different genetic regions may have
>different intrinsic mutation rates. This brings into play the different
>mechanisms that can account for mutation, such as gene conversion which play
>an important role in creating great heterogeneity in the MHC genes of many
>(not all) species.
Thus, MHC genes do not have just the normal "mutation" -- they do gene
conversions. (Gene conversion is no ordinary mutation, rather it morphs
information together from two separate sequences.) This situation is
peculiar because gene conversion does not seem to be used routinely by
mammals -- EXCEPT in the case of MHC genes (and MHC-like pseudogenes). Once
again, genes of the immune system stand out: 1) They have a high "mutation
rate". And 2) at least in mammals they have an unordinarily tight
association with gene conversion.
Recently I overheard that some pseudogenes are the result of, in some sense
inserted by, viruses. And that caused me to speculate a mechanism that
'closes the loop' on the rapid acquisition of immunity. Imagine it like
this. A viral infection might eventually spread to the germ cells, where a
virus inserts some genetic material. Eventually (perhaps through a skip and
a jump) some of this same genetic material is merged into the MHC genes via
gene conversion. The MHC genes would then contain "information" about the
virus that it did not have before -- information that would be of particular
help to the IMMUNE system, of which the MHC genes are a part. The immune
system would then have new information for identifying, and fighting future
infections from that family of viruses.
The information flow would be like this:
virus ----> pseudogene ---> ... ---> gene conversion into an MHC gene --->
immune system
This cycle might have to be traversed many times for the immune system to
fully acquire the necessary information on the virus.
I suspect Steve may be shaking his head in dismay at my taking such
liberties with the language and concepts of his field. It's all grist for
the Science mill.
Walter ReMine
P.O. Box 28006
Saint Paul, MN 55128