Evolution of MHC

L.A. Moran lamoran at gpu.utcs.utoronto.ca
Tue Aug 27 10:04:35 EST 1991

The genes of the mammalian MHC locus are polymorphic. One of these genes
has 50 known alleles and another has 47 in H. sapiens. I have three questions
for the immunologists, population biologists, and evolutionary biologists.

1. How many other examples of such heterozygosity in a population are known?

   (Futuyma gives the example of self-compatibility alleles in the evening
    primrose (45 alleles). The reference is from 1939, has more work been
    done recently? [see Futuyma, D.J. 1986, in EVOLUTIONARY BIOLOGY 2nd ed.
    p. 126])

2. How many other loci have been examined intensely?

   (It is technically difficult to look for alleles at most sites and there
    is little incentive to do so - unlike the case with transplantation
    antigens. Could the data on class I and class II genes be due to
    sampling bias? Maybe every gene that encodes an unconstrained protein
    would also have a large number of alleles if we looked. Does anyone know
    how many fibrinogen alleles there are in the H. sapiens population?)

3. Most of the allelic and evolutionary variation in class I molecules maps
   to the surface amino acids - including the peptide binding region. Is 
   this significant or is it simply due to the fact that amino acid
   substitutions that affect the exterior of the protein are much more likely
   to be detected immunologically? (In other words the assays select for those
   alleles that cause changes on the surface of the molecule.)

Laurence A. Moran (Larry)
Dept. of Biochemistry

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