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.

Y chromosome diversity, human expansion, drift, and cultural evolution

“…There probably was more need of biologic adaptations, and therefore of natural selection in the second phase, to meet challenges due to profound differences in diet and increased contact with domesticated animals and their contagious diseases. Examples in different parts of the world are pigmentation (33), lactose tolerance (34)(35)(36), and increase of genetic resistances to malaria (37,38). Cultural evolution became much more effective than biologic evolution in meeting perceived needs, and may have almost replaced it, but every novelty has costs in addition to benefits, and thus much of natural selection may now be directed to take care of specific costs generated by cultural evolution, which were, however, not too severe, at least so far.…”

Genomic signatures of diet-related shifts during human origins

“…The most prominent example is the ability to digest milk solids (lactose) into adulthood (lactase persistence) in some human populations [2,3,74,75]. Multiple regulatory polymorphisms in these different populations help drive lactose-phlorizin hydrolase (LPH) gene expression in adults.…”

“…In contrast, the functional impact of regulatory SNPs throughout the genome is currently not well understood. Specific examples such as the regulatory variants that confer lactose tolerance (the ability to drink milk after weaning) in multiple populations [2,3,74,75] are known, suggesting that more are present and may be found in future functional genomic studies.…”

Milk Consumption is Not Affected by C/T-13910 Single Nucleotide Polymorphism in a Tajik Population in a Southern Region of Uzbekistan

“…In European ancestry, nucleotide polymorphism C/T -13910 originated about 7500 BC in the Balkans and Central Europe (archaeological Linearbandkeramik and Starčevo cultures) and then spread to the east, towards India, and north Africa [8,9]. Stable lactose absorption in the adult population in the area of sub-Saharan Africa has evolved independently from the European lineage with C/T-13910 mutation associated with the breeding of Arabian camels [10].…”