title: An ancient balanced polymorphism in a regulatory region of human major histocompatibility complex is retained in Chinese minorities but lost worldwide.
abstract: The coding regions of many of the major histocompatibility complex (MHC) (human leukocyte antigen [HLA] in humans) molecules are believed to be subject to balancing selection. But it is less certain whether the regulatory regions of such coding sequences are also subject to the same type of selection. Here, we studied the polymorphism of the regulatory regions of the HLA-DPA1 and HLA-DPB1 genes among ethnic minorities in southwestern China. Phylogenetic analysis revealed two deep clades >10 million years old. There is almost complete linkage disequilibrium between the regulatory and coding regions of HLA-DPA1, which hints 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. Although the frequency of clade II is >30% in some ethnic minorities, it decreases to <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 may thus contribute disproportionately to the total diversity of modern humans.
authors.affiliation: State Key Laboratory for Biocontrol, Department of Biochemistry, Key Laboratory of Genetic Engineering of the Ministry of Education, College of Life Sciences, Sun Yat-sen Zhongshan University, Guangzhou, China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Liu
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Fu
authors.forename: Zehuan
authors.initials: Z
authors.lastname: Liu
authors.forename: Bin
authors.initials: B
authors.lastname: Lin
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Yin
authors.initials: Y
authors.lastname: Liu
authors.forename: Yunpin
authors.initials: Y
authors.lastname: Xu
authors.forename: Jianghai
authors.initials: J
authors.lastname: Lin
authors.forename: Xinlan
authors.initials: X
authors.lastname: Fan
authors.forename: Meiling
authors.initials: M
authors.lastname: Dong
authors.forename: Kai
authors.initials: K
authors.lastname: Zeng
authors.forename: Chung-I
authors.initials: CI
authors.lastname: Wu
authors.forename: Anlong
authors.initials: A
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D005802:Genes, MHC Class II / Q000235:genetics*; D006682:HLA-DP Antigens / Q000145:classification / Q000235:genetics*; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D010802:Phylogeny; D011110:Polymorphism, Genetic; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*
chemical_list: D006682:HLA-DP Antigens; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen