title: Herders of Indian and European cattle share their predominant allele for lactase persistence.
abstract: Milk consumption and lactose digestion after weaning are exclusively human traits made possible by the continued production of the enzyme lactase in adulthood. Multiple independent mutations in a 100-bp region--part of an enhancer--approximately 14-kb upstream of the LCT gene are associated with this trait in Europeans and pastoralists from Saudi Arabia and Africa. However, a single mutation of purported western Eurasian origin accounts for much of observed lactase persistence outside Africa. Given the high levels of present-day milk consumption in India, together with archaeological and genetic evidence for the independent domestication of cattle in the Indus valley roughly 7,000 years ago, we sought to determine whether lactase persistence has evolved independently in the subcontinent. Here, we present the results of the first comprehensive survey of the LCT enhancer region in south Asia. Having genotyped 2,284 DNA samples from across the Indian subcontinent, we find that the previously described west Eurasian -13910 C>T mutation accounts for nearly all the genetic variation we observed in the 400- to 700-bp LCT regulatory region that we sequenced. Geography is a significant predictor of -13910*T allele frequency, and consistent with other genomic loci, its distribution in India follows a general northwest to southeast declining pattern, although frequencies among certain neighboring populations vary substantially. We confirm that the mutation is identical by descent to the European allele and is associated with the same>1 Mb extended haplotype in both populations.
authors.affiliation: Department of Biological Anthropology, Leverhulme Centre for Human Evolutionary Studies, University of Cambridge, Cambridge, United Kingdom. ireneg@uchicago.edu
authors.forename: Irene
authors.initials: I
authors.lastname: Gallego Romero
authors.forename: Chandana
authors.initials: C
authors.lastname: Basu Mallick
authors.forename: Anke
authors.initials: A
authors.lastname: Liebert
authors.forename: Federica
authors.initials: F
authors.lastname: Crivellaro
authors.forename: Gyaneshwer
authors.initials: G
authors.lastname: Chaubey
authors.forename: Yuval
authors.initials: Y
authors.lastname: Itan
authors.forename: Mait
authors.initials: M
authors.lastname: Metspalu
authors.forename: Muthukrishnan
authors.initials: M
authors.lastname: Eaaswarkhanth
authors.forename: Ramasamy
authors.initials: R
authors.lastname: Pitchappan
authors.forename: Richard
authors.initials: R
authors.lastname: Villems
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.forename: Lalji
authors.initials: L
authors.lastname: Singh
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
authors.forename: Mark G
authors.initials: MG
authors.lastname: Thomas
authors.forename: Dallas M
authors.initials: DM
authors.lastname: Swallow
authors.forename: Marta
authors.initials: M
authors.lastname: Mirazón Lahr
authors.forename: Toomas
authors.initials: T
authors.lastname: Kivisild
mesh_terms: D000822:Animal Husbandry; D000818:Animals; D002417:Cattle; D019143:Evolution, Molecular; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D007194:India; D043322:Lactase / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D044465:White People / Q000235:genetics*
chemical_list: D043322:Lactase