Reconstructing the evolutionary history of humans and human-associated microbes in South Asia using an integrated genomics approach

研究总结 南亚人占全球人口的近25%，表现出独特而复杂的遗传和 社会结构。南亚人还表现出传染病和非传染性疾病的沉重负担。然而， 缺乏来自南亚血统个人的现代和古代基因组数据，导致 关于该区域遗传和社会文化多样性的起源和演变的零散图景。完毕 在接下来的五年里，Raghavan实验室的一个主要研究项目将利用我们在 古代和现代基因组学解决三个关键主题，以促进我们对遗传学的理解 南亚人及其疾病：(一)过去8000年的区域人口历史，(二) 史前传染病的发生及病原体和传染病的演变 以及(Iii)饮食转变对印度人肠道微生物群组成和健康的影响 人口。因为今天的基因库和疾病图景是长期进化的产物 过程中，我们将联合生成和分析古代和现代人类基因组数据集，以便 实现主题1和主题2，重点是现代人类人口的演变，包括重建 过去的迁徙和混杂事件以及传染病，包括检测和系统发育 分别对人类骨骼材料中的古代病原体进行表征。主题3将另外 受益于我的组织与印度各地土著居民日益增长的网络，以研究 饮食和生存的转变--所谓的传统饮食的西方化--对肠道微生物群的影响。 最终，通过落实南亚背景下的这些互补主题 这项研究计划将有助于我们对进化的全面理解 人类人口健康和疾病的基础机制。重要的是，数据和结果来自 我们的研究将解决基因组学文献中关键的代表性差距，并使精确医学 努力在应用方面更加普遍和多样化，特别是对于一个区域来说，鉴于它是 人口最稠密、散居国外人数最多的地区，极大地加重了全球疾病负担。

Research Summary South Asians account for nearly 25% of the global population, displaying unique and complex genetic and social structures. South Asians also exhibit a high burden of infectious and non-infectious diseases. Yet, the paucity of modern and ancient genomics data deriving from individuals of South Asian ancestry, result in a fragmented picture of the origins and evolution of the genetic and socio-cultural diversity of this region. Over the next five years, one of primary research programs in the Raghavan lab will leverage our expertise in ancient and modern genomics to address three crucial themes to promote our understanding of the genetics of South Asians and their diseases: (i) the regional demographic history over the last ~8,000 years, (ii) the prehistoric occurrence of infectious diseases and the evolution of pathogens and infectious diseases in this region, and (iii) the impact of dietary transitions on the gut microbiome composition and health of Indian populations. Since present-day gene pools and disease landscapes are products of long-acting evolutionary processes, we will jointly generate and analyze ancient and modern human genomic datasets in order to achieve Themes 1 and 2 that focus on the evolution of modern human populations, including reconstructing past migrations and admixture events, and infectious diseases, including the detection and phylogenetic characterization of ancient pathogens in human skeletal materials, respectively. Theme 3 will additionally benefit from my group’s growing networks with Indigenous populations across India to study the impact of dietary and subsistence transitions – so-called ‘westernization’ of traditionalist diets - on the gut microbiome. Ultimately, through the implementation of these complementary themes set within the context of South Asian populations, this research program will contribute towards our overall understanding of the evolutionary mechanisms that underlie health and disease among human populations. Importantly, data and results from our research will address critical representational gaps in the genomics literature and make precision medicine efforts more universal and diverse in their application, especially for a region that, in light of being one of the most populous regions with the largest diaspora, contributes substantially to the global disease burden.