Revisiting the demographic history of Central African populations from a genetic perspective

Africa is the continent of our species’ origin and the deep history of humans is represented by African genetic variation. Through genetic studies, it has become evident that deep African population history is captured by relationships among African hunter-gatherers and that the world’s deepest population divergences occur among these groups. In this review, we look back at a study published by Cavalli-Sforza and colleagues in 1969 entitled “Studies on African Pygmies. I. A pilot investigation of Babinga Pygmies in the Central African Republic (with an analysis of genetic distances)”. The study analyzed 19 classical polymorphisms and found that the deepest divergences in African populations were represented by hunter-gatherer groups such as the southern African San and the central African rainforest hunter-gatherers. We repeated the original analyses from Cavalli-Sforza et al. [1] with about 22 thousand times more genome-wide genetic markers in populations similar to those included in the original study. Our high-resolution analyses gave similar results regarding the relationships of early-diverging African populations compared to the classical polymorphism analyses. This finding, however, does not imply that research has stagnated and that developments in technology and genetic methods over the last fifty years delivered no additional information regarding African history and adaptation. We review how technology and population genetic methods have advanced to give more detailed inferences about population structure, migrations, admixture patterns, timing of admixture, sex-biased admixture, and inferences of selection and adaptive introgression in rainforest hunter-gatherers and other African populations. We also comment on how sequencing of ancient DNA has influenced findings and deliberate on the progress and development of more complex models of African history, including alternatives to tree-models and the inference of possible archaic admixture in African populations. We review the growing complexity of our picture of population history in central Africa and Africa as a whole, emerging from genomic studies and other disciplines investigating human population history and adaptation. While data and knowledge are accumulating, certain populations and areas remain underrepresented in genomic research. Their inclusion, possibly also through ancient DNA studies, together with new methods of analysis and the testing of representative models of deep population history in Africa, will help to build a more complete picture of past population history in Africa. Based on “Cavalli-Sforza LL, Zonta LA, Nuzzo F, Bernini L, de Jong WW, Meera Khan P, Ray AK, Went LN, Siniscalco M, Nijenhuis LE, van Loghem E, Modiano G. Studies on African Pygmies. I. A pilot investigation of Babinga Pygmies in the Central African Republic (with an analysis of genetic distances). Am J Hum Genet. 1969 May;21(3):252-274”.

A Genome Scan for Genes Underlying Adult Body Size Differences between Central African Pygmies and their Non-Pygmy Neighbors

BackgroundCentral African hunter-gatherer Pygmy populations have reduced body size compared with their often much larger agricultural non-Pygmy neighbors, potentially reflecting adaptation to the anatomical and physiological constraints of their lifestyle in tropical rainforests. Earlier studies investigating the genetics of the pygmy phenotype have focused on standing height, one aspect of this complex phenotype that is itself a composite of skeletal components with different growth patterns. Here, we extend the investigations of standing height to the variability and genetic architecture of sitting height and subischial leg length as well as body mass index (BMI) in a sample of 406 unrelated West Central African Pygmies and non-Pygmies.ResultsIn addition to their significantly reduced standing height compared with non-Pygmies, we find Pygmies to have significantly shorter sitting heights and subischial leg lengths as well as higher sitting/standing height ratios than non-Pygmies. However, while male Pygmies had significantly lower BMI compared with male non-Pygmies, the BMI of females were instead similar. Consistent with prior observations with standing height, sitting height and subischial leg length were strongly correlated with inferred levels of non-Pygmy genetic admixture while BMI was instead weakly correlated, likely reflecting the greater contribution of non-genetic factors to the determination of body weight compared with height. Using 196,725 SNPs on the Illumina Cardio-MetaboChip with genotypes on 358 Pygmy and 169 non-Pygmy individuals together with single-and multi-marker association approaches, we identified a single genomic region and seven genes associated with Pygmy/non-Pygmy categorization as well as 9, 10, 9, and 10 genes associated with standing and sitting height, sitting/standing height ratio, and subischial leg length, respectively. Many of the genes identified have putative functions consistent with a role in determining their associated trait as well as the complex Central African pygmy phenotype.ConclusionsThese findings highlight the potential of modestly sized datasets of Pygmies and non-Pygmies to detect biologically meaningful associations with traits contributing to the Central African pygmy phenotype. Moreover, they provide new insights into the phenotypic and genetic bases of the complex pygmy phenotype and offer new opportunities to facilitate our understanding of its complex evolutionary origins.