Alain Froment

Origins and Genetic Diversity of Pygmy Hunter-Gatherers from Western Central Africa

Central Africa is currently peopled by numerous sedentary agriculturalist populations neighboring the largest group of mobile hunter-gatherers, the Pygmies [1-3]. Although archeological remains attest to Homo sapiens presence in the Congo Basin for at least 30,000 years, the demographic history of these groups, including divergence and admixture, remains widely unknown [4-6]. Moreover, it is still debated whether common history or convergent adaptation to a forest environment resulted in the short stature characterizing the pygmies [2, 7]. We genotyped 604 individuals at 28 autosomal tetranucleotide microsatellite loci in 12 nonpygmy and 9 neighboring pygmy populations. We found a high level of genetic heterogeneity among Western Central African pygmies, as well as evidence of heterogeneous levels of asymmetrical gene flow from nonpygmies to pygmies, consistent with the variable sociocultural barriers against intermarriages. Using approximate Bayesian computation (ABC) methods [8], we compared several historical scenarios. The most likely points toward a unique ancestral pygmy population that diversified approximately 2800 years ago, contemporarily with the Neolithic expansion of nonpygmy agriculturalists [9, 10]. Our results show that recent isolation, genetic drift, and heterogeneous admixture enabled a rapid and substantial genetic differentiation among Western Central African pygmies. Such an admixture pattern is consistent with the various sociocultural behaviors related to intermariages between pygmies and nonpygmies.

Inferring the demographic history of African farmers and pygmy hunter-gatherers using a multilocus resequencing data set.

The transition from hunting and gathering to farming involved a major cultural innovation that has spread rapidly over most of the globe in the last ten millennia. In sub-Saharan Africa, hunter–gatherers have begun to shift toward an agriculture-based lifestyle over the last 5,000 years. Only a few populations still base their mode of subsistence on hunting and gathering. The Pygmies are considered to be the largest group of mobile hunter–gatherers of Africa. They dwell in equatorial rainforests and are characterized by their short mean stature. However, little is known about the chronology of the demographic events—size changes, population splits, and gene flow—ultimately giving rise to contemporary Pygmy (Western and Eastern) groups and neighboring agricultural populations. We studied the branching history of Pygmy hunter–gatherers and agricultural populations from Africa and estimated separation times and gene flow between these populations. We resequenced 24 independent noncoding regions across the genome, corresponding to a total of ∼33 kb per individual, in 236 samples from seven Pygmy and five agricultural populations dispersed over the African continent. We used simulation-based inference to identify the historical model best fitting our data. The model identified included the early divergence of the ancestors of Pygmy hunter–gatherers and farming populations ∼60,000 years ago, followed by a split of the Pygmies ancestors into the Western and Eastern Pygmy groups ∼20,000 years ago. Our findings increase knowledge of the history of the peopling of the African continent in a region lacking archaeological data. An appreciation of the demographic and adaptive history of African populations with different modes of subsistence should improve our understanding of the influence of human lifestyles on genome diversity.

Variation in Rural African Gut Microbiota Is Strongly Correlated with Colonization by Entamoeba and Subsistence.

The human gut microbiota is impacted by host nutrition and health status and therefore represents a potentially adaptive phenotype influenced by metabolic and immune constraints. Previous studies contrasting rural populations in developing countries to urban industrialized ones have shown that industrialization is strongly correlated with patterns in human gut microbiota; however, we know little about the relative contribution of factors such as climate, diet, medicine, hygiene practices, host genetics, and parasitism. Here, we focus on fine-scale comparisons of African rural populations in order to (i) contrast the gut microbiota of populations inhabiting similar environments but having different traditional subsistence modes and either shared or distinct genetic ancestry, and (ii) examine the relationship between gut parasites and bacterial communities. Characterizing the fecal microbiota of Pygmy hunter-gatherers as well as Bantu individuals from both farming and fishing populations in Southwest Cameroon, we found that the gut parasite Entamoeba is significantly correlated with microbiome composition and diversity. We show that across populations, colonization by this protozoa can be predicted with 79% accuracy based on the composition of an individuals gut microbiota, and that several of the taxa most important for distinguishing Entamoeba absence or presence are signature taxa for autoimmune disorders. We also found gut communities to vary significantly with subsistence mode, notably with some taxa previously shown to be enriched in other hunter-gatherers groups (in Tanzania and Peru) also discriminating hunter-gatherers from neighboring farming or fishing populations in Cameroon.

Climate-associated anthropometric variation between populations of the Niger bend

A large set of measurements were taken on 512 women and 425 men belonging to ten populations of the Niger bend area, some of which live in the Sahelian, the other in the Sudanian climatic zones about 200 km apart. The two zones differ chiefly by a two-fold higher annual rainfall in the Sudanian zone. The pattern of differences in body weight, skinfold and limb circumferences suggests that the Sahelians allot proportionally more food and/or less physical work to women than the Sudanians . In one or both sexes, Sahelians have significantly longer lower limbs and forearms, larger hands and ears, a narrower face, and a higher and narrower nose. Sexual dimorphism of the shoulder-hip-width proportions is lower in the Sahelians , resulting from the Sahelian males, but not females, having wider hips, whereas Sahelians of both sexes have narrower shoulders. Multivariate analysis using D2 distances shows Sahelian and Sudanian populations forming two separate clusters, with the exception of the Dogon . In the male sex, nose width and sitting height account for the total multivariate interpopulational variation; nose width alone separates the two zonal groups, again with the Dogon as an exception. The position of the Dogon near to Sudanian populations while living in the Sahelian zone is explained by their migration from the Sudanian zone a few centuries ago. Adaptative genetic response to climate is proposed as a partial explanation of the evidence presented.

Trends in DNA Methylation with Age Replicate Across Diverse Human Populations

Aging is associated with widespread changes in genome-wide patterns of DNA methylation. Thousands of CpG sites whose tissue-specific methylation levels are strongly correlated with chronological age have been previously identified. However, the majority of these studies have focused primarily on cosmopolitan populations living in the developed world; it is not known if age-related patterns of DNA methylation at these loci are similar across a broad range of human genetic and ecological diversity. We investigated genome-wide methylation patterns using saliva- and whole blood-derived DNA from two traditionally hunting and gathering African populations: the Baka of the western Central African rain forest and the ≠Khomani San of the South African Kalahari Desert. We identified hundreds of CpG sites whose methylation levels are significantly associated with age, thousands that are significant in a meta-analysis, and replicate trends previously reported in populations of non-African descent. We confirmed that an age-associated site in the promoter of the gene ELOVL2 shows a remarkably congruent relationship with aging in humans, despite extensive genetic and environmental variation across populations. We also demonstrate that genotype state at methylation quantitative trait loci (meQTLs) can affect methylation trends at some age-associated CpG sites. Our study explores the relationship between CpG methylation and chronological age in populations of African hunter-gatherers, who rely on different diets across diverse ecologies. While many age-related CpG sites replicate across populations, we show that considering common genetic variation at meQTLs further improves our ability to detect previously identified age associations.

Variation in rural African gut microbiomes is strongly shaped by parasitism and diet

The human gut microbiota is impacted by host nutrition and health status and therefore represents a potentially adaptive phenotype influenced by metabolic and immune constraints. Previous studies contrasting rural populations in developing countries to urban industrialized ones have shown that industrialization is strongly correlated with patterns in human gut microbiota; however, we know little about the relative contribution of factors such as climate, diet, medicine, hygiene practices, host genetics, and parasitism. Here, we focus on fine-scale comparisons of African rural populations in order to (i) contrast the gut microbiota of populations inhabiting similar environments but having different traditional subsistence modes and either shared or distinct genetic ancestry, and (ii) examine the relationship between gut parasites and bacterial communities. Characterizing the fecal microbiota of Pygmy hunter-gatherers as well as Bantu individuals from both farming and fishing populations in Southwest Cameroon, we found that the gut parasite Entamoeba is significantly correlated with microbiome composition and diversity. We show that across populations, colonization by this protozoa can be predicted with 79% accuracy based on the composition of an individuals gut microbiota, and that several of the taxa most important for distinguishing Entamoeba absence or presence are signature taxa for autoimmune disorders. We also found gut communities to vary significantly with subsistence mode, notably with some taxa previously shown to be enriched in other hunter-gatherers groups (in Tanzania and Peru) also discriminating hunter-gatherers from neighboring farming or fishing populations in Cameroon. Author Summary The community of microorganisms inhabiting the gastrointestinal tract plays a critical role in determining human health. It’s been hypothesized that the industrialized lifestyle, marked by a diet rich in processed foods, higher use of antibiotics, increased hygiene, and exposure to various chemicals, has altered microbiota in ways that are harmful. Studies have addressed this by comparing rural and industrialized populations, and have found that they systematically vary in their gut microbiome composition. Nevertheless, the relative influence of host genetics, diet, climate, medication, hygiene practices, and parasitism is still not clear. In addition, microbial variation between nearby human populations has not been explored in depth. Moreover, The World Health Organization estimates that 24% of the world’s population, concentrated in developing countries, is infected with gut parasites. Despite this, and evidence for direct interactions between the immune system and both gut parasites and bacteria, we know relatively little about the relationship between gut helminths, protozoa, and bacteria. In our study, we aimed to address some of this complexity. To do so, we characterized the gut microbial communities and parasites from Pygmy hunter-gatherer and Bantu farming and fishing populations from seven locations in the rainforest of Southwest Cameroon. We found that both subsistence mode and the presence of the gut protozoa, Entamoeba, were significantly correlated with microbiome composition. These findings support previous studies demonstrating diet is an important determinant of gut microbiota, and further show that this pattern holds true at a local scale, in traditional societies inhabiting a similar environment. Additionally, we show a significant relationship between a common human parasite (Entamoeba) and gut bacterial community composition, suggesting potential important interactions between the immune system, gut bacteria, and gut parasites, highlighting the need for more hierarchical cross population studies that include parasitism as potential factor influencing gut microbiota dynamics.The human gut microbiome is influenced by its hosts nutrition and health status, and represents an interesting adaptive phenotype under the influence of metabolic and immune constraints. Previous studies contrasting rural populations in developing countries to urban industrialized ones have shown that geography is an important factor associated with the gut microbiome; however, studies have yet to disentangle the effects of factors such as climate, diet, host genetics, hygiene and parasitism. Here, we focus on fine-scale comparisons of African rural populations in order to (i) contrast the gut microbiomes of populations that inhabit similar environments but have different traditional subsistence modes and (ii) evaluate the effect of parasitism on microbiome composition and structure. We sampled rural Pygmy hunter-gatherers as well as Bantu individuals from both farming and fishing populations in Southwest Cameroon and found that the presence of Entamoeba is strongly correlated with microbial composition and diversity. Using a random forest classifier model, we show that an individuals infection status can be predicted with 79% accuracy based on his/her gut microbiome composition. We identified multiple taxa that differ significantly in frequency between infected and uninfected individuals, and found that alpha diversity is significantly higher in infected individuals, while beta-diversity is reduced. Subsistence mode was another factor significantly associated with microbial composition, notably with some taxa previously shown to differ between Hadza East African hunter-gatherers and Italians also discriminating Pygmy hunter-gatherers from neighboring farming or fishing populations in Cameroon. In conclusion, these results provide evidence for a strong relationship between human gut parasites and the microbiome, and highlight how sensitive this microbial ecosystem is to subtle changes in host nutrition.

Variations in the thickness of the cranial vault in a deformed skull from pre-Hispanic Ancón (Peru)

A medical tomodensitometric study (TDM) was performed on a dry skull from the necropolis of Ancón in Peru. The skull, housed at the Muséum national d’histoire naturelle in Paris, displays an anteroposterior, brachycephalic, oblique, asymmetric, and bilobar deformation. TDM permitted 3-D reconstructions of the skull, endocranium, and vault thickness. The external surface displayed deformation and asymmetry in the bone structures and the endocranium demonstrated deformation and asymmetry in the brain lobes and superficial structures. The TDM demonstration of abnormal variations and pronounced asymmetry in the thickness of the vault strongly suggested that the deformation was ante mortem. The 3-D TDM reconstructions also helped to reconstruct the device used to deform the head.RésuméUne étude tomodensitométrique (TDM) médicale a été réalisée sur un crâne sec de la nécropole d’Ancón au Pérou. Le crâne est conservé au Muséum national d’histoire naturelle à Paris. Il présente une déformation antéropostérieure, brachycéphale, oblique, asymétrique et bilobée. La TDM a permis la réalisation de reconstructions 3D du crâne, de l’endocrâne et de l’épaisseur de voûte. La surface externe montrait la déformation et l’asymétrie des structures osseuses. L’endocrâne montrait la déformation et l’asymétrie des lobes cérébraux, et les structures superficielles. La mise en évidence par TDM de variations anormales et d’une asymétrie marquée de l’épaisseur de voûte suggérait fortement que la déformation était ante mortem. De plus, les reconstructions 3D ont pu aider à la reconstitution de l’appareil déformateur.