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

成人体型是人类多样性中最明显、研究最多的方面之一。然而，大样本量的群体内遗传研究只能解释其遗传性的一小部分。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，历史上被称为“俾格米人”，因为他们的体型很小，他们的农业非俾格米人邻居通常要大得多，为探索人类体型的决定因素提供了一个强有力的框架。事实上，俾格米人的体型与非俾格米人祖先的水平密切相关，这表明他们的体型差异很大程度上可归因于遗传因素。本提案的主要目的是确定导致俾格米人和非俾格米人不同体型的基因和生物过程。长期目标是确定这些基因和过程在过去5 -7万年中这种差异的演变中的重要性，这些差异可能是适应不同的生态、健康和气候环境的结果。提出这一建议的一个主要动机是期望所获得的结果将为理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。这一提议的基本假设是，中非人决定体型的大多数基因和过程将与非非洲人共享，因此我们的发现将为更完整的人类发育生物学研究提供新的机会。这项提议的直接目标是收集9对俾格米人和邻近的非俾格米人的288个人的DNA、RNA和身体测量数据。使用最新的全基因组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文化和人口历史的关系；(2)确定对中非体型变化有重要影响的遗传因素和生物过程；(3)仔细研究自然选择是侏儒体型进化的驱动力的证据。这个项目将为我们对遗传基础和进化力量的理解提供重大进展，这些力量塑造了当代世界范围内的人体尺寸变化。

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.