Circum-Saharan Prehistory through the Lens of mtDNA Diversity.

African history has been significantly influenced by the Sahara, which has represented a barrier for migrations of all living beings, including humans. Major exceptions were the gene flow events that took place between North African and sub-Saharan populations during the so-called African Humid Periods, especially in the Early Holocene (11.5 to 5.5 thousand years ago), and more recently in connection with trans-Saharan commercial routes. In this study, we describe mitochondrial DNA (mtDNA) diversity of human populations from both sides of the Sahara Desert, i.e., both from North Africa and the Sahel/Savannah belt. The final dataset of 7213 mtDNA sequences from 134 African populations encompasses 470 newly collected and 6743 previously published samples, which were analyzed using descriptive methods and Bayesian statistics. We completely sequenced 26 mtDNAs from sub-Saharan samples belonging to the Eurasian haplogroup N1. Analyses of these N1 mitogenomes revealed their possible routes to the Sahel, mostly via Bab el-Mandab. Our results indicate that maternal gene flow must have been important in this circum-Saharan space, not only within North Africa and the Sahel/Savannah belt but also between these two regions.

Demographic history was a formative mechanism of the genetic structure for the taste receptor TAS2R16 in human populations inhabiting Africa's Sahel/Savannah Belt.

OBJECTIVES: Mode of subsistence is an important factor influencing dietary habits and the genetic structure of various populations through differential intensity of gene flow and selection pressures. Previous studies suggest that in Africa Taste 2 Receptor Member 16 (TAS2R16), which encodes the 7-transmembrane receptor protein for bitterness, might also be under positive selection pressure. METHODS: However, since sampling coverage of populations was limited, we created a new TAS2R16 population dataset from across the African Sahel/Savannah belt representing various local populations of differing subsistence modes, linguistic affiliations, and geographic provenience. We sequenced the TAS2R16 exon gene and analyzed 2250 haplotypes among 19 populations. RESULTS: We found no evidence for selection as a driving force of genetic variation at this locus; instead, we discovered a highly significant correlation between TAS2R16 genetic and geographical distances based on provenience of the sampled populations, strongly suggesting that genetic drift most likely prevailed over positive selection at this specific locus. We also found significant correlations with other independent loci, mainly in sedentary farmers. DISCUSSION: Our results do not support the notion that the genetic diversity of TAS2R16 in Sahelian populations was shaped by selective pressures. This could result from several alternative and not mutually exclusive mechanisms, of which the possibility that, due to the pleiotropic nature of TAS2R16, selective pressures on other traits could counterbalance those acting on bitter taste perception, or that the change of diet in the Neolithic generally relaxed selective pressure on this gene.

Safety of the Geneva Cocktail, a Cytochrome P450 and P-Glycoprotein Phenotyping Cocktail, in Healthy Volunteers from Three Different Geographic Origins.

INTRODUCTION AND OBJECTIVE: Cytochrome P450 enzymes are the major drug-metabolizing enzymes in humans and the importance of drug transport proteins, in particular P-glycoprotein, in the variability of drug response has also been highlighted. Activity of cytochrome P450 enzymes and P-glycoprotein can vary widely between individuals and genotyping and/or phenotyping can help assess their activity. Several phenotyping cocktails have been developed. The Geneva cocktail is composed of a specific probe for six different cytochrome P450 enzymes and one for P-glycoprotein and was used in the context of a research aiming at exploring genotypes and phenotypes in distinct human populations (NCT02789527). The aim of the present study is to solely report the safety results of the Geneva cocktail in the healthy volunteers of these populations. MATERIALS AND METHODS: The Geneva cocktail is composed of caffeine, bupropion, flurbiprofen, omeprazole, dextromethorphan, midazolam, and fexofenadine. The volunteers fasted and avoided drinking caffeine-containing beverages or food and grapefruit juice overnight before receiving the cocktail orally. They provided blood spots for the probes' concentrations at 2, 3, and 6 h after ingestion and were asked about adverse events. RESULTS: A total of 265 healthy adult volunteers were included from Ethiopia, Oman, and the Czech Republic. The mean plasma concentrations at the 2-h sampling time of each probe drug in the total sample were: 1663 ng/mL for caffeine, 8 ng/mL for bupropion, 789 ng/mL for flurbiprofen, 6 ng/mL for dextromethorphan, 2 ng/mL for midazolam, 35 ng/mL for fexofenadine, and 103 ng/mL for omeprazole. Four adverse events were observed representing an occurrence of 1.5%. All these events were categorized as mild to moderate, non-serious, and resolved spontaneously. A causal link with the cocktail cannot be excluded because of the temporal relationship but is at most evaluated as possible according to the World Health Organization-Uppsala Monitoring Centre causal assessment system. CONCLUSIONS: In this research, healthy volunteers from three different human populations were phenotyped with the Geneva cocktail. Four adverse events were observed, confirming the safety of this cocktail that is given at lower than clinically relevant doses and therefore results in concentrations lower than those reported to cause adverse events.

Internal diversification of non-Sub-Saharan haplogroups in Sahelian populations and the spread of pastoralism beyond the Sahara.

BACKGROUND: Today, African pastoralists are found mainly in the Sahel/Savannah belt spanning 6,000 km from west to east, flanked by the Sahara to the north and tropical rainforests to the south. The most significant group among them are the Fulani who not only keep cattle breeds of possible West Eurasian ancestry, but form themselves a gene pool containing some paternally and maternally-transmitted West Eurasian haplogroups. MATERIALS AND METHODS: We generated complete sequences for 33 mitogenomes belonging to haplogroups H1 and U5 (23 and 10, respectively), and genotyped 16 STRs in 65 Y chromosomes belonging to haplogroup R1b-V88. RESULTS: We show that age estimates of the maternal lineage H1cb1, occurring almost exclusively in the Fulani, point to the time when the first cattle herders settled the Sahel/Savannah belt. Similar age estimates were obtained for paternal lineage R1b-V88, which occurs today in the Fulani but also in other, mostly pastoral populations. Maternal clade U5b1b1b, reported earlier in the Berbers, shows a shallower age, suggesting another possibly independent input into the Sahelian pastoralist gene pool. CONCLUSIONS: Despite the fact that animal domestication originated in the Near East ∼ 10 ka, and that it was from there that animals such as sheep, goats as well as cattle were introduced into Northeast Africa soon thereafter, contemporary cattle keepers in the Sahel/Savannah belt show uniparental genetic affinities that suggest the possibility of an ancient contact with an additional ancestral population of western Mediterranean ancestry.

Genetic Structure of the Western and Eastern African Sahel/Savannah Belt and the Role of Nomadic Pastoralists as Inferred from the Variation of D-Loop Mitochondrial DNA Sequences.

The objective of this study was to provide deeper knowledge of the maternal genetic structure and demographic history of the human populations of the Sahel/Savannah belt, the extensive region lying between the Sahara and tropical rainforests, spanning from the Atlantic Ocean to the Red Sea coast. The study aimed to confirm or disconfirm archaeological and linguistic data indicating that the region's populations underwent diversification as a result of the spread of agropastoral food-producing subsistence lifestyles, over time dividing the region into separate areas of nomadic pastoralism, on the one hand, and sedentary farming, on the other. To perform both descriptive and coalescence analyses from the Sahel/Savannah belt's entire region, including western and eastern rather than just central populations studied previously, we generated a new mitochondrial DNA (mtDNA) data set not only having almost 2,000 samples (875 of which were newly collected) but also encompassing whole mtDNA D-loop segment rather than only the previously studied hypervariable segment 1. While comparing our analyses with previous results from the Lake Chad Basin (central Sahel/Savannah Belt), we found similar intrapopulation diversity measures (i.e., lower values in pastoralists than in farmers). However, the new data set pointed to significant differences in mating strategies between western and eastern pastoralists: our results suggest higher gene flow between the Arabic pastoralists and neighboring farmers in the eastern part than between the Fulani pastoralists and their sedentary neighbors in the western part of the Sahel/Savannah belt. The findings are discussed in light of archaeological and linguistic data, allowing us to postulate that the genetic differentiation of Fulani pastoralists from the common western African agropastoral gene pool occurred at around the same time as the arrival of the Arabic pastoralists to eastern Africa. However, it seems that while the process of divergence of the Fulani pastoralists in the west was accompanied by a loss of Fulani females to other populations, the Arab pastoralists' immigration to the Sahel/Savannah belt conversely resulted in some gain of local females into this Arab population.