Monday, March 10, 2008

Still more on climate and metabolic "disease" genes

Dan MacArthur at Genetic Future has looked more closely at the recent climate-metabolic genes paper that I briefly touched on (here, here). He makes the point that the correlation between allele frequency and temperature (for example) need not be linear and will differ by population depending on its' particular history:
... Native Americans, for instance, are the descendants of a cold-adapted population living in Siberia that only relatively recently moved down into the warmer climates of central America; selection has not yet had much time to act in these populations. In contrast, humans in Southern Asia have been in their current climate much longer, giving selection more time to do its work. Thus for variants under positive selection, current frequency will be substantially affected by historical contingencies, and the correlation between allele frequency and selective strength will be rough at best.
Dan also finds that only one of the sixteen genes that they examine shows any signs of positive selection using the iHS measure of selection.
His main argument is that balancing selection would probably better explain the pattern they find than positive selection. I think the main thrust behind his argument is the last paragraph:
A heterozygote advantage situation should be seen as an imperfect and temporary solution to the problem of adaptation, one that evolution uses during the earliest phase of adaptation in the absence of anything better. Ultimately, human populations are likely to stumble across more elegant long-term solutions: fixation (by positive selection) of more subtle "tweaking" mutations that adapt the population to its local climate, without the troublesome handicap of also causing disease in homozygotes. Once this has happened, studies such as this one based on simple allele frequency would be completely unable to uncover climate adaptation genes.
Razib has commented on this post also and is somewhat skeptical about the importance of balancing selection. At some point I will really read this paper more closely. I even printed it out a few days ago!

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