A comprehensive whole genome sequence scan for positive selection in southern Africa

项目总结 现代人的非洲血统和该地区巨大的基因多样性是无可辩驳的。在 非洲，南部非洲是世界上最古老和最多样化的现存人类群体的家园。 这些种群，科桑人，主要居住在南非西北部和整个 纳米比亚和博茨瓦纳。在之前的工作(PMID 27474727)中，我和我的两位导师展示了细微的尺度 这些科桑种群之间的遗传种群结构反映了生态地理边界。在……里面 除了这种独特的科桑血统之外，南部非洲的人口还由许多 来自非洲境内(例如说班图语的民族)和非洲以外(特别是欧洲和亚洲)的移民 种群)。因此，在该地区观察到的多样性模式是独一无二的，没有可比的地区。 在世界其他地方。这些南部非洲人继续进一步适应他们的新环境 那里饱受疾病、资源限制和恶劣气候的困扰。正向选择在这方面的作用 适应，仍然是未知的。 使用最大的全基因组测序数据集集合之一，包含众多 南部非洲人口，我们的目标是：1)扫描这些数据集，寻找积极选择的信号；2)评估 这些信号的功能、生物学和潜在的翻译含义。这个项目将是世界上最大的 对非洲大陆自然选择的最全面的单一研究。中开发的方法 这项研究将为未来在异种、混合的非洲种群中进行自然选择的扫描提供信息。 此外，这些发现将提供对环境适应如何塑造人类的洞察力 基因组，进而，非洲这一独特地区的各种表型--这些结果可能会为所有人提供信息 具有非洲血统的人口。

PROJECT SUMMARY An African origin for modern humans and the vast genetic diversity in the region is irrefutable. Within Africa, southern Africa is home to the some of the oldest and most diverse extant human populations world-wide. These populations, the KhoeSan, reside predominantly in the north-western parts of South Africa and throughout Namibia and Botswana. In previous work (PMID 27474727), I and two of my mentors showed that fine-scale genetic population structure between these KhoeSan populations reflects ecogeographical boundaries. In addition to this unique KhoeSan ancestry, populations in southern Africa have been shaped by numerous migrations from within Africa (e.g. Bantu-speaking peoples) and outside Africa (notably European and Asian populations). Thus, the patterns of diversity observed in this area is unique with no comparable regions elsewhere in the world. These southern African populations went on to further adapt to their new environment which was plagued by disease, resource limitations and harsh climates. The role of positive selection in this adaption, remains unknown. Using one of the largest whole genome sequencing dataset collections encompassing numerous southern African populations, we aim to: 1) scan these datasets for signals of positive selection and 2) evaluate the functional, biological and potentially translational implications of these signals. This project will be the largest and most comprehensive single study of natural selection on the African continent. The methods developed in this study will inform future scans for natural selection in heterogenous, admixed African populations. Furthermore, the findings will provide insights into how adaptation to the environment has shaped human genomes and in turn, various phenotypes in this unique part of Africa - these results could be informative to all populations with African ancestry.