Doctoral Dissertation Research: Ancient Genomics and the Molecular Mechanisms of Human Tolerance to Arsenic

博士论文研究：古代基因组学与人类砷耐受的分子机制

• 批准号: 2142160
• 负责人: Anne Stone
• 金额: $ 3.14万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2142160&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Research; Ancient; Genomics

Arsenic causes severe toxicological effects in humans, yet some human populations have evolved to tolerate this element. Today, people in some regions may carry protective mutations in a key enzyme that metabolizes arsenic in the liver. However, several aspects remain unclear about the evolutionary history and genetic basis of arsenic tolerance. This doctoral dissertation research project therefore examines the genetic history, modes of subsistence, and gene regulatory mechanisms in ancient and modern DNA samples from populations exposed to arsenic. The findings can expand our understanding of biocultural processes through which humans are able to adapt to their environment. The project also supports student mentorship and training opportunities for undergraduate and graduate students, opportunities for international research collaborations, and science dissemination through conferences and social media.This project is centered on the understanding of the cultural and biological diversity of ancient and modern populations living in an arsenic rich region. Specifically, three main questions are addressed: (1) what are the genetic history and relationships among ancient and modern populations? (2) how did the transition to agriculture impact diet and oral health? and (3) what role/function do the mutations associated with arsenic tolerance play in the expression of the AS3MT gene? The researcher reconstructs the genetic prehistory of the region using ancient DNA and modern genomic data. In addition, oral microbiome data from ancient dental calculus are used to characterize the prehistoric diet, oral health and environmental exposures among pre-agricultural and agricultural populations. Third, genetic sequences carrying protective mutations are used to assess experimentally whether they alter/regulate the expression of the AS3MT gene in vitro.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

砷对人类造成严重的毒理学影响，但一些人群已经进化到可以耐受这种元素。今天，某些地区的人可能在肝脏中代谢砷的关键酶中携带保护性突变。然而，关于砷耐受性的进化历史和遗传基础，有几个方面仍然不清楚。因此，本博士论文的研究项目探讨了遗传史，生存模式，和基因调控机制在古代和现代的DNA样本暴露于砷。这些发现可以扩大我们对人类能够适应环境的生物文化过程的理解。该项目还为本科生和研究生提供学生导师和培训机会，提供国际研究合作机会，并通过会议和社交媒体传播科学。该项目的核心是了解生活在砷丰富地区的古代和现代人群的文化和生物多样性。具体而言，主要涉及三个问题：（1）古代和现代人群之间的遗传历史和关系是什么？(2)向农业的过渡如何影响饮食和口腔健康？（3）与砷耐受相关的突变在AS 3 MT基因表达中起什么作用？研究人员利用古代DNA和现代基因组数据重建了该地区的遗传史前史。此外，来自古代牙石的口腔微生物组数据被用来描述史前饮食，农业前和农业人口的口腔健康和环境暴露。第三，携带保护性突变的基因序列用于实验评估它们是否改变/调节AS 3 MT基因的体外表达。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。