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

项目摘要 现代人类的非洲起源和该地区巨大的遗传多样性是无可辩驳的。内 非洲南部非洲是世界上现存最古老和最多样化的人口的家园。 这些人口，KhoeSan人，主要居住在南非西北部和整个 纳米比亚和博茨瓦纳。在以前的工作（PMID 27474727）中，我和我的两位导师表明， 这些KhoeSan种群之间的遗传种群结构反映了生态地理边界。在 除了这种独特的KhoeSan血统，南部非洲的人口还受到许多因素的影响， 来自非洲内部（如班图语民族）和非洲外部（特别是欧洲和亚洲）的移民 人口）。因此，在这一地区观察到的多样性模式是独一无二的，没有可比较的区域 在世界其他地方。这些南部非洲的人口继续进一步适应他们的新环境 受到疾病、资源限制和恶劣气候的困扰。积极选择在其中的作用 适应性尚不清楚。 使用最大的全基因组测序数据集之一， 我们的目标是：1）扫描这些数据集的积极选择信号，2）评估 这些信号的功能、生物学和潜在的翻译含义。这个项目将是最大的 也是对非洲大陆自然选择最全面的单一研究。开发的方法 这项研究将为未来在异质混合的非洲种群中进行自然选择的研究提供信息。 此外，研究结果将为了解对环境的适应如何塑造人类提供见解 基因组，反过来，在非洲这个独特的地区的各种表型-这些结果可能是信息给所有人 有非洲血统的人。

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.