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Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture |
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| Authors: | Enattah Nabil Sabri Jensen Tine G K Nielsen Mette Lewinski Rikke Kuokkanen Mikko Rasinpera Heli El-Shanti Hatem Seo Jeong Kee Alifrangis Michael Khalil Insaf F Natah Abdrazak Ali Ahmed Natah Sirajedin Comas David Mehdi S Qasim Groop Leif Vestergaard Else Marie Imtiaz Faiqa Rashed Mohamed S Meyer Brian Troelsen Jesper Peltonen Leena |
| Affiliation: | 1 Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, 00251 Helsinki, Finland, and Department of Medical Genetics, University of Helsinki, Biomedicum Helsinki, 00251 Helsinki, Finland 2 Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK, and The Broad Institute, MIT, Cambridge, MA 02141-2023, USA 3 Department of Cellular and Molecular Medicine, Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark 4 Division of Medical Genetics, University of Iowa Hospital &; Clinics, 2615 JCP, 200 Hawkins Drive, Iowa City, IA 52242, USA 5 Department of Pediatrics, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul 110-774, Korea 6 Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, CSS, University of Copenhagen, 1014 Copenhagen, Denmark 7 Program of Natural Sciences, Faculty of Science, University of Calgary, Alberta T2N 1N4, Canada 8 Department of Physiology, Biophysics and Medicine, Gastrointestinal Division, Health Sciences Center, University of Calgary, Alberta T2N 1N4, Canada 9 Department of Anatomy, Institute of Clinical Medicine, University of Helsinki, 00014 Helsinki, Finland 10 Department of Evolutionary Biology, Faculty of Health and Life Sciences, University of Pompeu Fabra, 08003 Barcelona, Spain 11 Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi, 75270 Karachi, Pakistan 12 Department of Endocrinology, Malmö University Hospital, S-205 02 Malmö, Sweden 13 Department of Clinical Biochemistry, Aarhus University Hospital, DK 8000 Aarhus, Denmark 14 Arabian Diagnostics Laboratory, Research Centre, King Faisal Specialist Hospital &; Research Centre, Riyadh 11211, Saudi Arabia 15 National Newborn Screening Laboratory, Research Centre, King Faisal Specialist Hospital &; Research Centre, Riyadh 11211, Saudi Arabia |
| Abstract: | The T−13910 variant located in the enhancer element of the lactase (LCT) gene correlates perfectly with lactase persistence (LP) in Eurasian populations whereas the variant is almost nonexistent among Sub-Saharan African populations, showing high prevalence of LP. Here, we report identification of two new mutations among Saudis, also known for the high prevalence of LP. We confirmed the absence of the European T−13910 and established two new mutations found as a compound allele: T/G−13915 within the −13910 enhancer region and a synonymous SNP in the exon 17 of the MCM6 gene T/C−3712, −3712 bp from the LCT gene. The compound allele is driven to a high prevalence among Middle East population(s). Our functional analyses in vitro showed that both SNPs of the compound allele, located 10 kb apart, are required for the enhancer effect, most probably mediated through the binding of the hepatic nuclear factor 1 α (HNF1α). High selection coefficient (s) ~0.04 for LP phenotype was found for both T−13910 and the compound allele. The European T−13910 and the earlier identified East African G−13907 LP allele share the same ancestral background and most likely the same history, probably related to the same cattle domestication event. In contrast, the compound Arab allele shows a different, highly divergent ancestral haplotype, suggesting that these two major global LP alleles have arisen independently, the latter perhaps in response to camel milk consumption. These results support the convergent evolution of the LP in diverse populations, most probably reflecting different histories of adaptation to milk culture. |
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