Dan MacArthur has a post up, Climate genes: positive or balancing selection?, where he questions the interpretation of data from a recent paper, Adaptations to Climate in Candidate Genes for Common Metabolic Disorders:
The critical point I want to make is that while positive selection will usually tend to increase the frequency of an allele until it reaches 100% frequency, balancing selection can result in a situation where an allele reaches a stable frequency that is less than 100%. For a case of heterozygote advantage, the stable frequency will be the point at which the selective advantage of heterozygotes is cancelled out by the selective disadvantage of homozygotes.
Read the whole post. I've had some of the same thoughts as Dan before. I guess my main issue is that I am generally cautious about interpreting data as evidence of heterozygote advantage. There are theoretical reasons for this; if you have a bunch of loci where this is operant you're implying a range in fitness which just doesn't seem reasonable. Only a small proportion of the population would exhibit the exact range of combinations of heterozygote after heterozygote state which would be of maximum fitness. W. D. Hamilton was very skeptical of heterozygote advantage as a major evolutionary force. Richard Lewontin is my main source for the theoretical objection. So I tend to think there's something to that objection. But the objection makes assumptions about the way fitness adds or multiplies across loci which might not hold. Nature can surprise us. I'm generally more sympathetic to frequency dependent selection as maintaining polymorphism, but I don't know exactly how this would work for climate related genes. I suppose with heterozygote advance one of the homozygote states (two derived copies) could have only a minimal fitness decrement. For example: Homozygote ancestral = 0.7 Heterozygote = 1.0 Homozygote derived = 0.95 I get an equilibrium allele frequency for the derived adaptive mutant at 86%. One assumes that during the early stages of the increase in frequency it basically looks like straight positive selection, with the break coming up only as the frequency gets really high and the homozygotes segregating out start to serve as genetic load....
