Positive Selection in East Asians for an EDAR Allele That Enhances NF-kappaB Activation

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 May 22

PMID 18493316

Citations 49

Authors

Jaroslaw Bryk

Emilie Hardouin

Irina Pugach

David Hughes

Rainer Strotmann

Mark Stoneking

Sean Myles

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Multiple-testing corrections in selection scans using identity-by-descent segments.

Temple S, Browning S bioRxiv. 2025; .

PMID: 39975073 PMC: 11838353. DOI: 10.1101/2025.01.29.635528.

IL-6-174 G/C transversion might decrease male infertility risk: A case-control study.

Zamani-Badi T, Karimian M, Mahabadi J, Rafatmanesh A, Nikzad H Int J Reprod Biomed. 2025; 22(12):1015-1024.

PMID: 39968364 PMC: 11830927. DOI: 10.18502/ijrm.v22i12.18067.

PITX2 expression and Neanderthal introgression in HS3ST3A1 contribute to variation in tooth dimensions in modern humans.

Li Q, Faux P, Winchester E, Yang G, Chen Y, Ramirez L Curr Biol. 2024; 35(1):131-144.e6.

PMID: 39672157 PMC: 11789201. DOI: 10.1016/j.cub.2024.11.027.

Thermal Adaptations in Animals: Genes, Development, and Evolution.

Agata A, Nomura T Adv Exp Med Biol. 2024; 1461:253-265.

PMID: 39289287 DOI: 10.1007/978-981-97-4584-5_18.

Novel genetic associations with five aesthetic facial traits: A genome-wide association study in the Chinese population.

Wang P, Sun X, Miao Q, Mi H, Cao M, Zhao S Front Genet. 2022; 13:967684.

PMID: 36035146 PMC: 9411802. DOI: 10.3389/fgene.2022.967684.

References

Lamason R, Mohideen M, Mest J, Wong A, Norton H, Aros M . SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans. Science. 2005; 310(5755):1782-6. DOI: 10.1126/science.1116238. View

Bersaglieri T, Sabeti P, Patterson N, Vanderploeg T, Schaffner S, Drake J . Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet. 2004; 74(6):1111-20. PMC: 1182075. DOI: 10.1086/421051. View

Kumar A, Eby M, Sinha S, Jasmin A, Chaudhary P . The ectodermal dysplasia receptor activates the nuclear factor-kappaB, JNK, and cell death pathways and binds to ectodysplasin A. J Biol Chem. 2000; 276(4):2668-77. DOI: 10.1074/jbc.M008356200. View

Thornton K, Jensen J . Controlling the false-positive rate in multilocus genome scans for selection. Genetics. 2006; 175(2):737-50. PMC: 1800626. DOI: 10.1534/genetics.106.064642. View

Cann H, De Toma C, Cazes L, Morel V, Piouffre L, Bodmer J . A human genome diversity cell line panel. Science. 2002; 296(5566):261-2. DOI: 10.1126/science.296.5566.261b. View

Sabeti P, Fry B, Lohmueller J, Hostetter E, Cotsapas C, Xie X . Genome-wide detection and characterization of positive selection in human populations. Nature. 2007; 449(7164):913-8. PMC: 2687721. DOI: 10.1038/nature06250. View

Frisse L, Hudson R, Bartoszewicz A, Wall J, Donfack J, Di Rienzo A . Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels. Am J Hum Genet. 2001; 69(4):831-43. PMC: 1226068. DOI: 10.1086/323612. View

Fischer A, Wiebe V, Paabo S, Przeworski M . Evidence for a complex demographic history of chimpanzees. Mol Biol Evol. 2004; 21(5):799-808. DOI: 10.1093/molbev/msh083. View

Izagirre N, Garcia I, Junquera C, de la Rua C, Alonso S . A scan for signatures of positive selection in candidate loci for skin pigmentation in humans. Mol Biol Evol. 2006; 23(9):1697-706. DOI: 10.1093/molbev/msl030. View

10.

Barreiro L, Laval G, Quach H, Patin E, Quintana-Murci L . Natural selection has driven population differentiation in modern humans. Nat Genet. 2008; 40(3):340-5. DOI: 10.1038/ng.78. View

11.

Fagundes N, Ray N, Beaumont M, Neuenschwander S, Salzano F, Bonatto S . Statistical evaluation of alternative models of human evolution. Proc Natl Acad Sci U S A. 2007; 104(45):17614-9. PMC: 2077041. DOI: 10.1073/pnas.0708280104. View

12.

Norton H, Kittles R, Parra E, McKeigue P, Mao X, Cheng K . Genetic evidence for the convergent evolution of light skin in Europeans and East Asians. Mol Biol Evol. 2006; 24(3):710-22. DOI: 10.1093/molbev/msl203. View

13.

Botchkarev V, Fessing M . Edar signaling in the control of hair follicle development. J Investig Dermatol Symp Proc. 2005; 10(3):247-51. DOI: 10.1111/j.1087-0024.2005.10129.x. View

14.

Rosenberg N . Standardized subsets of the HGDP-CEPH Human Genome Diversity Cell Line Panel, accounting for atypical and duplicated samples and pairs of close relatives. Ann Hum Genet. 2006; 70(Pt 6):841-7. DOI: 10.1111/j.1469-1809.2006.00285.x. View

15.

Akey J, Eberle M, Rieder M, Carlson C, Shriver M, Nickerson D . Population history and natural selection shape patterns of genetic variation in 132 genes. PLoS Biol. 2004; 2(10):e286. PMC: 515367. DOI: 10.1371/journal.pbio.0020286. View

16.

Lao O, de Gruijter J, van Duijn K, Navarro A, Kayser M . Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms. Ann Hum Genet. 2007; 71(Pt 3):354-69. DOI: 10.1111/j.1469-1809.2006.00341.x. View

17.

Franbourg A, Hallegot P, Baltenneck F, Toutain C, Leroy F . Current research on ethnic hair. J Am Acad Dermatol. 2003; 48(6 Suppl):S115-9. DOI: 10.1067/mjd.2003.277. View

18.

Soejima M, Tachida H, Ishida T, Sano A, Koda Y . Evidence for recent positive selection at the human AIM1 locus in a European population. Mol Biol Evol. 2005; 23(1):179-88. DOI: 10.1093/molbev/msj018. View

19.

Ptak S, Hinds D, Koehler K, Nickel B, Patil N, Ballinger D . Fine-scale recombination patterns differ between chimpanzees and humans. Nat Genet. 2005; 37(4):429-34. DOI: 10.1038/ng1529. View

20.

Hey J . On the number of New World founders: a population genetic portrait of the peopling of the Americas. PLoS Biol. 2005; 3(6):e193. PMC: 1131883. DOI: 10.1371/journal.pbio.0030193. View