South of the Sahara, the semi-arid Sahel/Savannah belt with its short and unstable rainy season is home to two ecologically different subsistence strategies – nomadic pastoralists and sedentary farmers. The origin of food production systems in this area is still not fully understood. Some scholars hold that a mixed agropastoral economy complemented with hunting, fishing and gathering was developed from ~ 4 kya onwards, and that the divergence between pastoral nomads and sedentary farmers into the modalities that are known today took place only recently. According to other scholars, however, Sahelian pastoralism based on meat and milk consumption from domesticated animals is older than the sedentary farming based on consumption of polysaccharides from domesticated cereals. While each Sahelian population might rely on a specific traditional diet, it is expected that common nutrients are shared by groups of populations with the same mode of subsistence (such as lactose consumption by pastoralists), and this motivates our interest for the evolution of genes involved in the metabolism of exogenous substances to the organism. By comparing genetic and genomic diversity of Sahelian nomadic pastoralists and sedentary farmers, and by using molecular information to predict phenotype, we have evidenced signals of local adaptations to specific environmental and cultural conditions in several genes, such as LCT, NAT2 and TAS2R. Using a series of samples that have been both genotyped for six CYP genes and monitored for the enzymatic activity encoded, we are now applying the same predictive approach to investigate the evolution of these genes in herders and farmers of the African Sahel.