The origins of lactase persistence in Europe

Abstract

Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (-13,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the--13,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia's geographic space. Using data on--13,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the--13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe.

Figure 1. Approximate marginal posterior density estimates of demographic and evolutionary parameters.

ABC was performed using regression adjustment and weighting, following acceptance at the 0.5% tolerance level . The upper and lower 2.5% of each distribution are shaded. For some parameters the estimated 95% credible intervals lie outside the upper prior bound. This is a consequence of the regression adjustment stage of ABC when using rectangular priors . Points in which the parameter value is close to the boundary, but with summary statistics that are distant from those observed, can have their parameter values projected outside the boundary. Parameters estimated are (A) Interdemic bidirectional geneflow, (B) Intrademic bidirectional geneflow, (C) the rate of cultural diffusion of subsistence practices, (D) the selective advantage of a LP allele among dairying farmers, (E) the proportion of individuals in a deme available for sporadic long-distance migration, and the average mobility – in number of demes moved – of (F) hunter-gatherers, (G) non-dairying farmers, and (H) dairying farmers.

Figure 2. Pairwise joint approximate posterior density estimates of demographic and evolutionary parameters showing high degrees of correlation (Spearman's R²>0.024).

Points represent regression adjusted parameter values from simulations accepted at the 0.5% tolerance level. Shading was added using 2D kernel density estimation. Parameter combinations shown are the proportion of individuals in a deme available for sporadic long-distance migration versus the average mobility – in number of demes moved – of (A) dairying farmers, and (B) non-dairying farmers, (C) the selective advantage of a LP allele among dairying farmers versus the average mobility of non-dairying farmers, and (D) the average mobility of dairying farmers versus the average mobility of hunter-gatherers.

Figure 3. Approximate posterior density of region of origin for LP/dairying co-evolution.

Points represent regression-adjusted latitude and longitude coordinates from simulations accepted at the 0.5% tolerance level. Shading was added using 2D kernel density estimation.

Figure 4. Estimates of the date of origin for LP/dairying coevolution and the contribution of people living in the deme of origin for LP/dairying co-evolution, and its eight surrounding demes, to the modern European gene pool.

Although not parameters of the model sensu stricto, estimates were calculated as with all model parameters by using ABC with regression adjustment and weighting, following acceptance at the 0.5% tolerance level . The date of origin for LP/dairying coevolution (A) is given in thousands of years before present, and the contribution of people living in the deme of origin for LP/dairying co-evolution, and its 8 surrounding demes, to the modern European gene pool (B) is given as a percentage. The upper and lower 2.5% of each distribution are shaded.

Figure 5. Contribution of people living in the deme of origin for LP/dairying co-evolution, and its 8 surrounding demes, to the modern European gene pool with and without selection on LP.

Value distributions were taken from 5,000 simulations assuming selection (black line), and 5,000 simulations assuming no selection (red line). Simulation parameter values were sampled at random from the marginal posterior density estimates presented in Figure 1 and were identical for each set of 5,000 simulations, except that in the ‘no selection’ set the selection acting on the LP allele in dairyers parameter was set to zero.