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

研究综述 南亚人占全球人口的近25%，显示出独特而复杂的遗传和 社会结构。南亚人也表现出传染性和非传染性疾病的高负担。然而 缺乏来自南亚血统个体的现代和古代基因组学数据，导致 这是该地区遗传和社会文化多样性的起源和演变的支离破碎的画面。超过 在接下来的五年里，Raghavan实验室的主要研究项目之一将利用我们的专业知识， 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， 南亚人和他们的疾病：（i）过去8,000年的区域人口历史，（ii） 史前传染病的发生和病原体的演变以及传染病在此 地区，以及（iii）饮食转变对印度人肠道微生物组组成和健康的影响 人口。由于当今的基因库和疾病景观是长期进化的产物， 我们将共同生成和分析古代和现代人类基因组数据集， 实现主题1和2，重点是现代人类的进化，包括重建 过去的迁移和混合事件，以及传染病，包括检测和系统发育 分别表征人类骨骼材料中的古代病原体。主题3还将 我受益于我的小组与印度各地土著居民日益增长的网络， 饮食和生计的转变--所谓的传统饮食的“西化”--对肠道微生物的影响。 最后，通过落实这些在南亚区域背景下确定的互补主题， 人口，这项研究计划将有助于我们对进化的整体理解， 人类健康和疾病的基础机制。重要的是，数据和结果 我们的研究将解决基因组学文献中的关键代表性空白， 特别是对一个区域来说，鉴于它是世界上最不发达国家之一， 人口最多的地区和最大的散居地，大大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.