Re: Rapid origin of genetic variation

Steve Clark (ssclark@facstaff.wisc.edu)
Thu, 17 Aug 1995 19:59:33 -0500

Walter writes:
>Glenn cites examples of high levels of genetic variation:
>
>>There was a recent Scientific American article on the MHC
>>(major histocompatibility complex) which has to do with our
>>immune system, in which they listed up to 59 known alleles
>>Scientific American Dec. 1993, p. 78.
>
>>Klein, in his book, _The Natural History of the Major
>>Histocompatibility Complex, (New York: 1986), p. 627
>>lists locations in the mouse genome which have up to
>>92 known alleles.
>
>Glenn's examples of high genetic variation were selected by him and do not
>represent typical cases. His examples all involve the (MHC) genes which are
>central to the immune system. These particular genes must recognize 'self'
>from 'foreign' and readily key-in on new types of foreign tissue. They do
>that by rapidly mutating and recombining in an effort to find a key that
>matches the foreign tissue.

This is not correct science, Walter. You confuse antigen receptor genes
(immunoglobulin and T cell receptors) with MHC genes. Antigen receptor
proteins are what the immune system uses to distinguish self from foreign,
not MHC proteins. The so-called variable regions of antigen receptor genes
undergo a high rate of SOMATIC mutation which helps explain why the immune
system can recognize such a vast array of foreign molecules, including
synthetic ones never seen before in nature. This variability arises from
point mutation within a narrow region of the antigen receptor gene.

MHC genes, on the other hand, are involved in antigen presentation to the
immune cells, and do NOT distinguish between self and foreign antigens, as
you claim. MHC loci display what Jan Klein once claimed to be the highest
rate of GERMLINE mutation in the mammalian genome. This mutation occcurs
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.

For the sake of the evolution debate, only GERMLINE mutations are relevant.
These occur in germ cells (sperm and ova) and hence are heritable and fixed
in a species gene pool. In contrast, SOMATIC mutation occurs in cells that
constitute tissues and organs of an individual's body and are not passed
along to its progeny. Hence, these mutations do not factor into any sort of
evolutionary mechanism.

Walter's analysis combines the best of these two type of genes and mutations.

Shalom,

Steve Clark, PhD Immunogenetics
____________________________________________________________________________
Steven S. Clark, Ph.D. Phone: (608) 263-9137
Associate Professor FAX: (608) 263-4226
Dept. of Human Oncology and email: ssclark@facstaff.wisc.edu
UW Comprehensive Cancer Ctr
University of Wisconsin "To disdain philosophy is really to
Madison, WI 53792 be a philosopher." Blaise Pascal
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