Impact of selection and demography on the diffusion of lactase persistence

Abstract

Background: The lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches.

Methodology: We first analyse the distribution of lactase persistence in various continents in relation to geographic variation, pastoralism levels, and the genetic patterns observed for other independent polymorphisms. Then we use computer simulations and a large database of archaeological dates for the introduction of domestication to explore the evolution of these frequencies in Europe according to different demographic scenarios and selection intensities.

Conclusions: Our results show that gene-culture coevolution is a likely hypothesis in Africa as high LCT*P frequencies are preferentially found in pastoral populations. In Europe, we show that population history played an important role in the diffusion of lactase persistence over the continent. Moreover, selection pressure on lactase persistence has been very high in the North-western part of the continent, by contrast to the South-eastern part where genetic drift alone can explain the observed frequencies. This selection pressure increasing with latitude is highly compatible with the calcium assimilation hypothesis while the gene-culture coevolution hypothesis cannot be ruled out if a positively selected lactase gene was carried at the front of the expansion wave during the Neolithic transition in Europe.

Figure 1. Map location of European and Near-Eastern populations used for the computer simulation.

Dots locate the populations used for computer simulation (Note that the Iran sample should be located farther East, outside of the map). When more than one population from the same country were used, the name of the corresponding city is given (see Table 3). Below each population name, the approximate date of domestication and its standard error (years BP) are mentioned. When simulating the Demic Diffusion hypothesis (DD), dotted arrows show the simulated relations between population source and "new founded" populations (regarding initial frequency of LCT*P, see Material and Methods and Supplementary Information). To facilitate reading, the dotted area regroups populations for which we use Greece as the source.

Figure 2. Selection coefficients required to fit the observed estimates of lactase persistence frequencies.

Each graph corresponds to one of the four scenario simulated: DD/gcc; DD/cal; CD/gcc; CD/cal (see Material and Methods). Bars represent the 95% CI of the selection coefficient estimated for the population and the central point is the MLE (Maximum Likelihood Estimate). Populations are ordered from the highest (right) to the lowest (left) latitude: Danish (Dan), Irish (Iri), German from Bremen (Bre), German from Berlin (Ber), English (Eng), Polish (Pol), Czech (Cze), German from Stuttgart (Stu), German from Munchen (Mun), Austrian (Aus), French from Nantes (Nan), Swiss (Swi), Slovenian (Slo), Italian from Brescia (Bre), French from Nice (Nic), Spanish from Santiago de Compostela (Com), Italian from Roma (Rom), Italian from Napoli (Nap), Sardinian (Sas), Spanish from Valencia (Val), Greek (Gre), Sicilian (Sic), Cypriot (Cyp), Lebanese (Leb) and Iranian (Ira).