Ancient balanced polymorphism preserved in Chinese ethnic minorities

Interesting preprint from AJHG which reports the discovery of a balanced polymorphism at high frequency in some Chinese ethnic minorities, at a smaller frequency in the Han, and its absence in Europeans and a limited sample of Africans. The great age of this polymorphism makes it a likely candidate for being of local East Asian origin before the emergence of anatomically modern humans.

American Journal of Human Genetics (preprint)

An ancient, balanced polymorphism in a regulatory region of human MHC is retained in Chinese minorities but lost worldwide

Xiaoyi Liu et al.

Summary

The coding regions of many MHC (HLA in human) molecules are believed to be subjected to balancing selection. But it is less certain whether the regulatory regions of such coding sequences are also subjected to the same type of selection. Here we studied the polymorphism of the regulatory regions of the HLA-DPA1 and -DPB1 genes among ethnic minorities in southwestern China. Phylogenetic analysis revealed two deep clades over 10 million years old. Linkage disequilibrium between the regulatory and coding regions of DPA1 is almost complete, hinting at coadaptive balancing selection on the entire region. Thus, the molecular mechanism of balancing selection in MHC may involve expression modulation, in addition to coding region polymorphisms. While the frequency of this polymorphism is greater than 30% in some ethnic minorities, it decreases to less than 5% among southern Han Chinese and vanishes among Europeans. As suspected, some ancient balanced polymorphisms, lost in major populations, still exist in isolated ethnicities. These isolated populations could thus contribute disproportionately to the total diversity of modern humans.