Convergent Adaptation of Human Lactase Persistance in Africa and Europe
ARTICLES
© 2007 Nature Publishing Group http://www.nature.com/naturegenetics
Convergent adaptation of human lactase persistence in Africa and Europe
Sarah A Tishkoff1,9, Floyd A Reed1,9, Alessia Ranciaro1,2, Benjamin F Voight3, Courtney C Babbitt4, Jesse S Silverman4, Kweli Powell1, Holly M Mortensen1, Jibril B Hirbo1, Maha Osman5, Muntaser Ibrahim5, Sabah A Omar6, Godfrey Lema7, Thomas B Nyambo7, Jilur Ghori8, Suzannah Bumpstead8, Jonathan K Pritchard3, Gregory A Wray4 & Panos Deloukas8
A SNP in the gene encoding lactase (LCT) (C/T-13910) is associated with the ability to digest milk as adults (lactase persistence) in Europeans, but the genetic basis of lactase persistence in Africans was previously unknown. We conducted a genotypephenotype association study in 470 Tanzanians, Kenyans and Sudanese and identified three SNPs (G/C-14010, T/G-13915 and C/G-13907) that are associated with lactase persistence and that have derived alleles that significantly enhance transcription from the LCT promoter in vitro. These SNPs originated on different haplotype backgrounds from the European C/T-13910 SNP and from each other. Genotyping across a 3-Mb region demonstrated haplotype homozygosity extending 42.0 Mb on chromosomes carrying C-14010, consistent with a selective sweep over the past B7,000 years. These data provide a marked example of convergent evolution due to strong selective pressure resulting from shared cultural traits—animal domestication and adult milk consumption. lactase persistence trait: C/T-13910 and G/A-22018, located B14 kb and B22 kb upstream of LCT, respectively, within introns 9 and 13 of the adjacent minichromosome maintenance 6 (MCM6) gene4 (Fig. 1). The T-13910 and A-22018 alleles were 100% and 97% associated with lactase persistence, respectively, in the Finnish study4, and the T-13910 allele is B86%–98% associated with lactase persistence in other European populations6–8. Although these alleles could simply be in LD with an unknown regulatory
© 2007 Nature Publishing Group http://www.nature.com/naturegenetics
Convergent adaptation of human lactase persistence in Africa and Europe
Sarah A Tishkoff1,9, Floyd A Reed1,9, Alessia Ranciaro1,2, Benjamin F Voight3, Courtney C Babbitt4, Jesse S Silverman4, Kweli Powell1, Holly M Mortensen1, Jibril B Hirbo1, Maha Osman5, Muntaser Ibrahim5, Sabah A Omar6, Godfrey Lema7, Thomas B Nyambo7, Jilur Ghori8, Suzannah Bumpstead8, Jonathan K Pritchard3, Gregory A Wray4 & Panos Deloukas8
A SNP in the gene encoding lactase (LCT) (C/T-13910) is associated with the ability to digest milk as adults (lactase persistence) in Europeans, but the genetic basis of lactase persistence in Africans was previously unknown. We conducted a genotypephenotype association study in 470 Tanzanians, Kenyans and Sudanese and identified three SNPs (G/C-14010, T/G-13915 and C/G-13907) that are associated with lactase persistence and that have derived alleles that significantly enhance transcription from the LCT promoter in vitro. These SNPs originated on different haplotype backgrounds from the European C/T-13910 SNP and from each other. Genotyping across a 3-Mb region demonstrated haplotype homozygosity extending 42.0 Mb on chromosomes carrying C-14010, consistent with a selective sweep over the past B7,000 years. These data provide a marked example of convergent evolution due to strong selective pressure resulting from shared cultural traits—animal domestication and adult milk consumption. lactase persistence trait: C/T-13910 and G/A-22018, located B14 kb and B22 kb upstream of LCT, respectively, within introns 9 and 13 of the adjacent minichromosome maintenance 6 (MCM6) gene4 (Fig. 1). The T-13910 and A-22018 alleles were 100% and 97% associated with lactase persistence, respectively, in the Finnish study4, and the T-13910 allele is B86%–98% associated with lactase persistence in other European populations6–8. Although these alleles could simply be in LD with an unknown regulatory