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

成年人的身体大小是人类多样性中最明显和研究最多的方面之一。然而，具有非常大样本量的群体内遗传研究只能解释其遗传力的一小部分。这一发现强调了人体尺寸的生物学复杂性，尽管它通常具有很高的遗传性。中非的狩猎采集者群体，历史上被称为“俾格米人”，因为他们身材矮小，他们的邻居通常是更大的农业非俾格米人，这为探索人类体型的决定因素提供了一个强大的框架。事实上，俾格米人的身体大小与非俾格米人的祖先水平密切相关，这表明他们的身体大小差异明显归因于遗传因素。这项建议的主要目的是查明造成俾格米人和非俾格米人体型不同的基因和生物过程。长期目标是确定这些基因和过程在过去50- 70，000年这种差异的进化中的重要性，这可能是适应不同生态，健康和气候环境的结果。该提案的一个主要动机是期望所获得的结果将为了解当代人体尺寸的演变及其在世界范围内的变化提供新的机会。这项提议的基本假设是，中非人中有助于体型决定的大多数基因和过程将与非非洲人共享，因此我们的研究结果将为人类发育生物学的更完整研究提供新的机会。这项计划的近期目标是收集来自9对俾格米人和邻近非俾格米人种群的288个个体的DNA、RNA和身体测量数据。利用最新的全基因组DNA和RNA测序方法，我们将：（1）探索俾格米人和非俾格米人的遗传和表型变异模式及其与中非人文化和人口历史的关系;（2）确定对中非人体型变异有重大影响的遗传因素和生物过程;以及（3）仔细研究自然选择是侏儒体型进化的驱动力的证据。该计划将为我们对全球范围内塑造当代人类体型变化的遗传基础和进化力量的理解提供重大进展。

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.