Health

A thought on antagonistic pleiotropy

Gene ExpressionBy Razib KhanAug 22, 2007 2:02 PM

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This is more of a quick note than a post. In Africa (and to a lesser extent other regions) the rise of malaria has resulted in an extreme evolutionary response, basically the heterozygote is extremely fit vis-a-vis mutant homozygotes (which exhibit Sickle Cell Anemia) and the wild type homozygotes. This is a case of balancing selection via overdominance, the frequencies of the alleles are determined by the fitness of the three genotypes (mutant homozygote, heterozygote and wild type homozygote). Naturally polymorphism will be maintained since the heterozygote by necessity needs the maintenance of genetic diversity to perpetuate its existence. It seems likely that this sort of adaptation is a short term response to extreme evolutionary pressures. If this flavor of heterozygote advantage was ubiquitous the segregation of homozygotes on so many loci would result in an implausible variance in fitness. It seems likely that over time evolution will come up with a less extreme adaptation, perhaps modifying the mutant allele in the case of malaria with other mutants which mask the deleterious impact of Sickle Cell Anemia. In the above case you have the extreme selective pressures resulting in a population wide trade off; the cost of extremely fit heterozygotes are the less fit homozygotes. But what about other scenarios where overdominance isn't an issue, but the trade off is temporal in terms of life history? I'm talking about a form of antagonistic pleiotropy. Here you have an allele which results in a large gain in short term fitness but may have long term consequences down stream. And in fact the cost later in life is minimal due to the reality that once one is beyond the peak reproductive years the fitness implications verge upon zero (though this may not be true for humans because of our sociality). Additionally, there are likely going to be plenty of short term correlated responses, which may have a minimal fitness implication. I think there will be some interesting evolutionary dynamics to be fleshed out in the processes which emerge out of the derivatives of selection as a function of time.

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