Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture.

Research output: Contribution to journalJournal articleResearchpeer-review

  • Nabil Sabri Enattah
  • Tine G K Jensen
  • Mette Boyd
  • Rikke Lewinski
  • Mikko Kuokkanen
  • Heli Rasinpera
  • Hatem El-Shanti
  • Jeong Kee Seo
  • Insaf F Khalil
  • Abdrazak Natah
  • Ahmed Ali
  • Sirajedin Natah
  • David Comas
  • S Qasim Mehdi
  • Leif Groop
  • Else Marie Vestergaard
  • Faiqa Imtiaz
  • Mohamed S Rashed
  • Brian Meyer
  • Jesper Troelsen
  • Leena Peltonen
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.
Original languageEnglish
JournalAmerican Journal of Human Genetics
Volume82
Issue number1
Pages (from-to)57-72
Number of pages15
ISSN0002-9297
DOIs
Publication statusPublished - 2008

Bibliographical note

Keywords: Alleles; Animals; Camels; Culture; Evolution, Molecular; Haplotypes; Humans; Lactase; Lactose Tolerance Test; Middle East; Milk; Polymorphism, Single Nucleotide; Saudi Arabia

ID: 5833537