A Tale of Two Haplotypes

The EDA2R/AR Intergenic Region is the Most Divergent Genomic Segment between Africans and East Asians in the Human Genome

Bibliographic Data

ID6067683
AuthorsAmanda M Casto (0000-0001-8332-8578, Stanford University), Brenna M Henn (0000-0003-4998-287X, Stanford University), Jeffery M Kidd, Jeffrey M Kidd (0000-0002-9631-1465, University of Michigan), Carlos D Bustamante (0000-0002-4187-7920, Stanford University), Marcus W Feldman (0000-0002-0664-3803, Stanford University)
Year2012
Volume84
Issue6
Pages641-694
Publication date2012-12-01
Open AccessNo
TypeARTICLE
VenueHuman Biology (JOURNAL)
Journal identifiersISSN: 0018-7143 • E-ISSN: 1534-6617
PublisherHuman Biology (The International Journal of Population Biology and Genetics) (PUBLISHER)
DOI10.3378/027.084.0604
PMID23959643
OpenAlexW4379517865, W2157851609
LanguageEN
References cited45

Single nucleotide polymorphisms (SNPs) with large allele frequency differences between human populations are relatively rare. The longest run of SNPs with an allele frequency difference of one between the Yoruba of Nigeria and the Han Chinese is found on the long arm of the X chromosome in the intergenic region separating the EDA2R and AR genes. It has been proposed that the unusual allele frequency distributions of these SNPs are the result of a selective sweep affecting African populations that occurred after the out-of-Africa migration. To investigate the evolutionary history of the EDA2R/AR intergenic region, we characterized the haplotype structure of 52 of its highly differentiated SNPs. Using a publicly available data set of 3,000 X chromosomes from 65 human populations, we found that nearly all human X chromosomes carry one of two modal haplotypes for these 52 SNPs. The predominance of two highly divergent haplotypes at this locus was confirmed by use of a subset of individuals sequenced to high coverage. The first of these haplotypes, the α-haplotype is at high frequencies in most of the African populations surveyed and likely arose before the separation of African populations into distinct genetic entities. The second, the β-haplotype, is frequent or fixed in all non-African populations and likely arose in East Africa before the out-of-Africa migration. We also observed a small group or rare haplotypes with no clear relationship to the α- and β-haplotypes. These haplotypes occur at relatively high frequencies in African hunter-gatherer populations, such as the San and Mbuti Pygmies. Our analysis indicates that these haplotypes are part of a pool of diverse, ancestral haplotypes that have now been almost entirely replaced by the α- and β-haplotypes. We suggest that the rise of the α- and β-haplotypes was the result of the demographic forces that human populations experienced during the formation of modern African populations and the out-of-Africa migration. However, we also present evidence that this region is the target of selection in the form of positive selection on the α- and β-haplotypes and of purifying the selection against α/β recombinants

1000 Genomes Project · Allele · Allele frequency · Biology · Evolutionary biology · Gene · Genome · Genotype · Haplotype · Human genome · Intergenic region · Locus (genetics · Single-nucleotide polymorphism · Forensic and Genetic Research · Genetic Associations and Epidemiology · Genetics · Genomic variations and chromosomal abnormalities

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