Genetics of body size among West Central African Pygmies and their non-Pygmy neighbors

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Adult body size is one of the most visible and most studied aspects of human diversity. However, within-population genetic studies with very large sample sizes have only been able to explain a minority of its heritability. This finding underscores the biological complexity of human body size despite its generally high heritability. ¬Central African hunter-gatherer populations, historically called “Pygmies” in reference to their diminutive body size, and their often much larger agricultural non-Pygmy neighbors provide a powerful framework within which to explore the determinants of human body size. Indeed, Pygmy body size is strongly correlated with levels of non-Pygmy ancestry, suggesting that their body size differences are significantly attributable to genetic factors. The primary objective of this proposal is to identify genes and biological processes contributing to the differing body size of Pygmies and non-Pygmies. A long-term goal is to determine the significance of these genes and processes in the evolution of this difference over the past 50-70,000 years possibly as the outcome of adaption to varying ecological, health, and climatic environments. A major motivation for the proposal is the expectation that the results obtained will provide new opportunities for understanding the evolution of contemporary human body size and its variation worldwide. The underlying hypothesis of this proposal is that a majority of genes and processes contributing to body size determination in Central Africans will be shared with non-Africans and thus our findings will provide new opportunities for more complete investigations of human developmental biology. The immediate goal of this proposal is to collect DNA, RNA, and body measurements for 288 individuals from nine pairs of Pygmy and neighboring non-Pygmy populations. Using the latest genome-wide DNA and RNA sequencing approaches we will: (1) explore patterns in genetic and phenotypic variation in Pygmies and non-Pygmies and their relationship with the cultural and demographic histories of Central Africans; (2) identify genetic factors and biological processes contributing significantly to Central African body size variation; and (3) scrutinise the evidence for natural selection being a driving force in the evolution of Pygmy body size. This program will provide significant advances in our understanding of the genetic bases and evolutionary forces that have shaped contemporary human body size variation worldwide.