title: Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture.
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 alpha (HNF1 alpha). High selection coefficient (s) approximately 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.
authors.affiliation: Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, 00251 Helsinki, Finland.
authors.forename: Nabil Sabri
authors.initials: NS
authors.lastname: Enattah
authors.forename: Tine G K
authors.initials: TG
authors.lastname: Jensen
authors.forename: Mette
authors.initials: M
authors.lastname: Nielsen
authors.forename: Rikke
authors.initials: R
authors.lastname: Lewinski
authors.forename: Mikko
authors.initials: M
authors.lastname: Kuokkanen
authors.forename: Heli
authors.initials: H
authors.lastname: Rasinpera
authors.forename: Hatem
authors.initials: H
authors.lastname: El-Shanti
authors.forename: Jeong Kee
authors.initials: JK
authors.lastname: Seo
authors.forename: Michael
authors.initials: M
authors.lastname: Alifrangis
authors.forename: Insaf F
authors.initials: IF
authors.lastname: Khalil
authors.forename: Abdrazak
authors.initials: A
authors.lastname: Natah
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ali
authors.forename: Sirajedin
authors.initials: S
authors.lastname: Natah
authors.forename: David
authors.initials: D
authors.lastname: Comas
authors.forename: S Qasim
authors.initials: SQ
authors.lastname: Mehdi
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Vestergaard
authors.forename: Faiqa
authors.initials: F
authors.lastname: Imtiaz
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Rashed
authors.forename: Brian
authors.initials: B
authors.lastname: Meyer
authors.forename: Jesper
authors.initials: J
authors.lastname: Troelsen
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000483:Alleles; D000818:Animals; D002162:Camelus; D003469:Culture; D019143:Evolution, Molecular; D006239:Haplotypes; D006801:Humans; D043322:Lactase / Q000235:genetics* / Q000378:metabolism; D007789:Lactose Tolerance Test; D008877:Middle East; D008892:Milk / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia
chemical_list: D043322:Lactase