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Tuesday, October 30, 2007

Diversity and the Major Histocompatibility Complex

 
A number of authors have applied this test [for homozygosity] to protein polymorphism data. In most cases, either no selection or purifying selection was indicated. In the case of human HLA (MHC) loci, however, Hedrick and Thomson (1983) found a significant reduction in homozygosity. It is, therefore, likely that the high polymorphism at these loci is maintained by some sort of balancing selection.

Masatoshi Nei (1987)
The adaptationist/pluralist debate really began in earnest with the discovery that there was much more genetic diversity in a population than expected if natural selection was the major mechanism of evolution [The Cause of Variation in a Population]. This lead to Neutral Theory and the recognition—by all but a few stubborn holdouts—that random genetic drift was responsible for most of evolution at the molecular level [Silent Mutations and Neutral Theory].

However, there are adaptationist explanations for diversity. They usually involve some form of balancing selection as is the case with sickle cell alleles in those parts of the world where malaria is a problem. Other versions of balancing selection are more complicated, especially those where the goal is to maintain multiple alleles that benefit the population as a whole.

The classic example is the major histocompatibility (MHC) locus that contains multiple alleles at the same genetic locus as well as multiple alleles segregating in the population. The case for selecting diversity seems strong.

In spite of the fact that this is an important concept I'm not going to touch this particular example since it's much too complicated. Fortunately for us, we have an immunologist blogger at Mystery Rays from Outer Space who works on antigen presentation. He bravely goes where Sandwalk fears to tread.

Read "Heavyweight championship: Overdominance vs. frequency-dependent selection" to see what the controversy is all about. If you need a refresher course on MHC class I molecules then "iayork" has that base covered as well [ It was twenty years ago today] [ MHC molecules: The sitcom].


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