Positive selection in East Asians for an EDAR allele that enhances NF-kappaB activation.

Bibliographic Collection: 
MOCA Reference, APE
Publication Type: Journal Article
Authors: Bryk, Jarosław; Hardouin, Emilie; Pugach, Irina; Hughes, David; Strotmann, Rainer; Stoneking, Mark; Myles, Sean
Year of Publication: 2008
Journal: PLoS One
Volume: 3
Issue: 5
Pagination: e2209
Date Published: 2008
Publication Language: eng
ISSN: 1932-6203
Keywords: Alleles, Asia, Edar Receptor, Humans, NF-kappa B, Selection, Genetic

Genome-wide scans for positive selection in humans provide a promising approach to establish links between genetic variants and adaptive phenotypes. From this approach, lists of hundreds of candidate genomic regions for positive selection have been assembled. These candidate regions are expected to contain variants that contribute to adaptive phenotypes, but few of these regions have been associated with phenotypic effects. Here we present evidence that a derived nonsynonymous substitution (370A) in EDAR, a gene involved in ectodermal development, was driven to high frequency in East Asia by positive selection prior to 10,000 years ago. With an in vitro transfection assay, we demonstrate that 370A enhances NF-kappaB activity. Our results suggest that 370A is a positively selected functional genetic variant that underlies an adaptive human phenotype.

DOI: 10.1371/journal.pone.0002209
Alternate Journal: PLoS ONE
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