Reviewing frequency-dependent selection on MHC

Mystery Rays from Outer Space wrote earlier this month about the pattern of selection on MHC, bringing up the question of whether overdominance (heterozygote advantage) or frequency dependence is the reigning pattern. This post focuses on some evidence supporting the hypothesis of frequency dependence.

Even on a short scale, alleles appear and disappear at a great rate. My favourite example of this is the map on the right 8 (I liked it so much I scanned it, years ago; I don't have access to the 1996 issues of Science on line. Click on the map for a larger version). This shows what happened to MHC diversity during the peopling of the Americas. You can see new alleles popping up down the migration route -- but the key point I want to make is made by the authors in a different paper: "Although many new HLA-B alleles have been produced in Latin America, their net effect has been to differentiate populations, not to increase allele diversity within a population."
In other words, rare old MHC alleles are not selected, but disappear, while rare new alleles are selected. This is consistent with the predictions of frequency-dependent selection than of overdominance, I think. But there are also lots of strong arguments for overdominant selection, some of which I'll mention next time around.

The post is notable for links back into the literature, and it will be interesting to see his next installment. Also in recent weeks he has posted a short review of the MHC molecules, and a look at how the structure of HLA-A2 was worked out.

That figure shows a little bit of undefined, unresolved mist (in pink) in the middle of the reasonably well-defined HLA-A2 molecule. The location of that little bit of mist, and its very mistiness, were the stunning part of the paper.

Oh, and a nice little post about MHC and the Tasmanian Devil tumor problem</a>. That's a good one for Halloween.

(via Sandwalk)