Understanding the genomic basis and evolutionary history of lactase persistence, and the dynamics of the associated gut microbiome, in pastoralist populations

了解牧民群体中乳糖酶持久性的基因组基础和进化历史，以及相关肠道微生物组的动态

• 批准号: 2221920
• 负责人: Michael Campbell
• 金额: $ 35万
• 依托单位: University of Southern California
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2221920&HistoricalAwards=false
• 关键词: Understanding; genomic; basis; evolutionary; history

This project addresses fundamental questions about the underlying genetics and evolutionary history of lactase persistence (LP), and the dynamics of the associated gut microbiome, in milk-dependent pastoralist populations. The findings of this study will work synergistically with previously collected archaeological data to advance the understanding of human population history. Moreover, the project will provide a more nuanced understanding of the factors that govern the diversity and relative abundance of host-associated microbiomes. In addition, the research facilitates the training of minority graduate students in the investigators’ research laboratories, enhancing their competitiveness and success in the STEM workforce. To further expand the impact of this research, a small subset of the collected genomic and phenotypic data will be analyzed in the investigators’ undergraduate courses at Howard University, introducing a greater cross-section of students to genetics, evolution, and computational methods through project-based activities. And beyond the classroom, this project will provide new opportunities for faculty with different scientific backgrounds (e.g. biological anthropology and microbiology) to explore research paths that do not traditionally fit into a single discipline. The investigators will collect genomic and phenotypic data in pastoralist populations, an understudied population. These data will be analyzed to: (1) identify novel LP-associated alleles and their possible interactions; (2) infer the evolutionary history of known and novel LP-associated loci; and (3) investigate the influence of host genetics and environment on gut microbial communities. Molecular data have provided some insights into the evolution of LP in humans, but thus far these studies have focused on specific well-studied populations This study provides information on additional populations thereby contributing to the genetic architecture and evolution of this uniquely human trait. With increased access to genome-wide and phenotypic data together with advances in computational methods, researchers are now able to examine new hypotheses about the genetic and microevolutionary factors that have influenced LP, as well as hypotheses about the genetic and environmental variables that have shaped the gut microbiome assemblage in milk-dependent populations. This project is jointly supported by the SBE-BCS Biological Anthropology Program and the SBE Office of Multidisciplinary Activities.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.

该项目解决了关于乳糖酶持久性（LP）的潜在遗传和进化历史的基本问题，以及相关肠道微生物组的动态，在依赖牛奶的牧民群体中。这项研究的发现将与先前收集的考古数据协同工作，以促进对人类人口历史的理解。此外，该项目将提供对控制宿主相关微生物群落多样性和相对丰度的因素的更细致的理解。此外，这项研究促进了少数民族研究生在研究实验室的培训，提高了他们在STEM劳动力中的竞争力和成功。为了进一步扩大这项研究的影响，研究人员将在霍华德大学的本科课程中分析收集的一小部分基因组和表型数据，通过基于项目的活动向更大范围的学生介绍遗传学、进化和计算方法。在课堂之外，该项目将为具有不同科学背景（如生物人类学和微生物学）的教师提供新的机会，以探索传统上不适合单一学科的研究路径。研究人员将收集牧民群体的基因组和表型数据，这是一个研究不足的群体。分析这些数据的目的是：(1)鉴定新的lp相关等位基因及其可能的相互作用；(2)推断已知和新的lp相关位点的进化史；(3)研究寄主遗传和环境对肠道微生物群落的影响。分子数据为人类LP的进化提供了一些见解，但到目前为止，这些研究都集中在特定的研究人群上。这项研究提供了关于其他人群的信息，从而为这一独特人类特征的遗传结构和进化做出了贡献。随着全基因组和表型数据的增加以及计算方法的进步，研究人员现在能够检验关于影响LP的遗传和微进化因素的新假设，以及关于影响牛奶依赖人群肠道微生物组组合的遗传和环境变量的假设。本项目由SBE- bcs生物人类学计划和SBE多学科活动办公室联合资助。该奖项反映了美国国家科学基金会的法定使命，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。