Positive Selection in East Asians for an EDAR Allele that Enhances NF-kB Activation

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-kB activity. Our results suggest that 370A is a positively selected functional genetic variant that underlies an adaptive human phenotype. Citation: Bryk J, Hardouin E, Pugach I, Hughes D, Strotmann R, et al. (2008) Positive Selection in East Asians for an EDAR Allele that Enhances NF-kB Activation. PLoS ONE 3(5): e2209. doi:10.1371/journal.pone.0002209 Editor: Jason E. Stajich, University of California, Berkeley, United States of America Received March 3, 2008; Accepted April 7, 2008; Published May 21, 2008 Copyright: 2008 Bryk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the German Bundesministerium für Bildung und Forschung (BMBF: NGFN2) and the Max Planck Society. Competing Interests: The authors have declared that no competing interests exist. * E-mail: [email protected] ¤ Current address: Institute for Genomic Diversity, Cornell University, Ithaca, New York, United States of America