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Copyright © 2007 The American Society of Human Genetics. All rights reserved.
The American Journal of Human Genetics, Volume 81, Issue 3, 615-625, 1 September 2007

doi:10.1086/520705

Report

Evidence of Still-Ongoing Convergence Evolution of the Lactase Persistence T_-13910 Alleles in Humans

Nabil Sabri Enattah^a, b, Aimee Trudeau^a, b, Ville Pimenoff^c, Luigi Maiuri^g, Salvatore Auricchio^g, Luigi Greco^g, Mauro Rossi^h, Michael Lentzeⁱ, J.K. Seo^j, Soheila Rahgozar^k, Insaf Khalil^l, Michael Alifrangis^l, Sirajedin Natah^m, Leif Groopⁿ, Nael Shaatⁿ, Andrew Kozlov^o, Galina Verschubskaya^o, David Comas^q, Kazima Bulayeva^p, S. Qasim Mehdi^r, Joseph D. Terwilliger^s, t, Timo Sahi^d, Erkki Savilahti^e, Markus Perola^a, b, Antti Sajantila^c, Irma Järvelä^f and Leena Peltonen^a, b, ,  

^a Department of Molecular Medicine, National Public Health Institute
^b Department of Medical Genetics, University of Helsinki, Biomedicum Helsinki
^c Department of Forensic Medicine
^d Department ofPublic Health
^e University of Helsinki, Finland Department of Pediatrics, Hospital for Children and Adolescents, Helsinki University Hospital, Helsinki
^f Helsinki University Central Hospital (HUSLAB), Helsinki Laboratory of Molecular Genetics, Helsinki
^g Department of Pediatrics, European Laboratory for Food Induced Diseases, University “Federico II,” Naples, Italy
^h Istituto di Scienze dell’Alimentazione, Consiglio Nazionale della Ricerche, Avellino, Italy
ⁱ Department of Pediatrics, Children’s Hospital, Medical Center, University of Bonn, Bonn, Germany
^j Department of Pediatrics, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul
^k Blood Transfusion Center, Esfahan, Iran
^l Panum Institute, Centre for Medical Parasitology, Institute of Medical Microbiology and Immunology, Copenhagen
^m Department of Physiology, Biophysics and Medicine (Gastrointestinal Division), Gastrointestinal Research Group, Health Sciences Center, University of Calgary, Alberta, Canada
ⁿ Department of Endocrinology, Malmö University Hospital, Malmö, Sweden
^o ArcAn-C Innovative Laboratory, Moscow
^p Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow
^q Unitat de Biologia Evolutiva, Facultat de Ciències de la Salut de la Vida, Universitat Pompeu Fabra, Barcelona
^r Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi, Karachi, Pakistan (S.Q.M.)
^s Department of Psychiatry and Columbia Genome Center, Columbia University
^t Division of Medical Genetics, New York State Psychiatric Institute, New York

Address for correspondence and reprints: Academy Prof. Leena Peltonen, Department of Medical Genetics and Molecular Medicine, University of Helsinki and National Public Health Institute, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland.

Abstract

A single-nucleotide variant, C/T_-13910, located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T_-13910 variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8–H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T_-13910 H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T_-13910 H98 allele (∼5,000–12,000 years old) is relatively older than the other geographically restricted LP alleles (∼1,400–3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T_-13910 allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.

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• Articles by Nabil Sabri Enattah
• Articles by Leena Peltonen

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