Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture.
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.
Enattah
Nabil Sabri
NS
Department of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, 00251 Helsinki, Finland.
Jensen
Tine G K
TG
Nielsen
Mette
M
Lewinski
Rikke
R
Kuokkanen
Mikko
M
Rasinpera
Heli
H
El-Shanti
Hatem
H
Seo
Jeong Kee
JK
Alifrangis
Michael
M
Khalil
Insaf F
IF
Natah
Abdrazak
A
Ali
Ahmed
A
Natah
Sirajedin
S
Comas
David
D
Mehdi
S Qasim
SQ
Groop
Leif
L
Vestergaard
Else Marie
EM
Imtiaz
Faiqa
F
Rashed
Mohamed S
MS
Meyer
Brian
B
Troelsen
Jesper
J
Peltonen
Leena
L
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
D043322:Lactase