If you follow our work, you may have remembered that we have published a paper on the curious evolution of genetic variation in the growth hormone receptor. Briefly, we have found that a deletion of the third exon of this gene has evolved as a response to starvation conditions. We followed up on this study to ask whether similar ancient variations exist in the human genome. To our surprise, we found that a considerable portion of common deletion polymorphisms are evolving under complex forms of balancing selection. These polymorphisms are primarily involved in immunity and metabolism. This paper, “Balancing selection on deletion polymorphisms in humans“, is now published in eLIFE.
A second follow-up of the growth hormone receptor (GHR) study led by Joni Nikkanen from Holly Ingraham’s group involved a conditional knock-out of the BCL6 gene in mice. In male mice livers, the effects of the GHR deletion and the conditional knockout have a similar effect, leading to female-like expression. What is pretty amazing is that the study documents a trade-off between fatty liver and susceptibility to certain types of bacterial infections.
So, I think there are now exciting new paths ahead. We now think that common disease-susceptibility variants may be understood at the intersection of metabolism, immunity, and balancing selection,