Adaptation to milk drinking and evolution of lactase persistence in pastoralist goat herders in central-northern Chile

Milk contains lactose as source of energy, which is digested by intestinal lactase, an enzyme that declines after weaning. The genetic trait of lactase persistence (LP) evolved together with the development of milking and pastoralism in the Old World as an adaptation to milk consumption in adults. The spread of this trait is one of the best examples of positive natural selection in humans. However, the specific mechanisms conferring selective advantages to LP are unknown. Milk drinking was introduced in the last 500 years to South America. To better understand the relationship between milk drinking, LP, growth, reproduction, and survival, this thesis explores the nature and extent of this dietary adaptation in the pastoralist communities of central–northern Chile, a population of mixed Amerindian and European ancestry, thus with persistent and non–persistent individuals. Data collected during 10 months of fieldwork consisted of questionnaires about reproduction and diet, DNA samples, and measurements of stature and weight of 450 participants. The lactase gene enhancer region was sequenced in all samples, and the European 13,910*T was the only LP–associated variant found. Phenotypes of 41 participants were established using hydrogen breath tests, showing strong association of this variant with phenotype. The frequency of LP in this population (0.38) is similar to that of non–pastoralist admixed populations of South America. To evaluate the effects of population structure, DNA analysis was used to study ancestry and relatedness. Controlling for these and other variables, the associations of LP and milk consumption with fertility, mortality, height and weight were assessed. We found no effect of LP on fertility, but a significant effect of LP on BMI and of BMI on fertility. These results suggest additional studies to evaluate the relationship between LP, BMI and fertility as an hypothesis of one of the possible routes to the positive selection for lactase persistence