title: Lactose digestion and the evolutionary genetics of lactase persistence.
abstract: It has been known for some 40 years that lactase production persists into adult life in some people but not in others. However, the mechanism and evolutionary significance of this variation have proved more elusive, and continue to excite the interest of investigators from different disciplines. This genetically determined trait differs in frequency worldwide and is due to cis-acting polymorphism of regulation of lactase gene expression. A single nucleotide polymorphism located 13.9 kb upstream from the lactase gene (C-13910 > T) was proposed to be the cause, and the -13910*T allele, which is widespread in Europe was found to be located on a very extended haplotype of 500 kb or more. The long region of haplotype conservation reflects a recent origin, and this, together with high frequencies, is evidence of positive selection, but also means that -13910*T might be an associated marker, rather than being causal of lactase persistence itself. Doubt about function was increased when it was shown that the original SNP did not account for lactase persistence in most African populations. However, the recent discovery that there are several other SNPs associated with lactase persistence in close proximity (within 100 bp), and that they all reside in a piece of sequence that has enhancer function in vitro, does suggest that they may each be functional, and their occurrence on different haplotype backgrounds shows that several independent mutations led to lactase persistence. Here we provide access to a database of worldwide distributions of lactase persistence and of the C-13910*T allele, as well as reviewing lactase molecular and population genetics and the role of selection in determining present day distributions of the lactase persistence phenotype.
authors.affiliation: Department of Genetics Evolution and Environment, University College London, London, UK.
authors.forename: Catherine J E
authors.initials: CJ
authors.lastname: Ingram
authors.forename: Charlotte A
authors.initials: CA
authors.lastname: Mulcare
authors.forename: Yuval
authors.initials: Y
authors.lastname: Itan
authors.forename: Mark G
authors.initials: MG
authors.lastname: Thomas
authors.forename: Dallas M
authors.initials: DM
authors.lastname: Swallow
mesh_terms: D000349:Africa; D000483:Alleles; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics; D004063:Digestion / Q000235:genetics; D019143:Evolution, Molecular; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D043322:Lactase / Q000235:genetics* / Q000378:metabolism*; D007785:Lactose / Q000378:metabolism*; D007787:Lactose Intolerance / Q000201:enzymology / Q000235:genetics; D007789:Lactose Tolerance Test; D064151:Minichromosome Maintenance Complex Component 6; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide
chemical_list: D018797:Cell Cycle Proteins; D043322:Lactase; C103258:MCM6 protein, human; D064151:Minichromosome Maintenance Complex Component 6; D007785:Lactose