Hominid Dental Metagenomes for Pathogen Evolution Research

用于病原体进化研究的原始牙齿宏基因组

• 批准号: 2045308
• 负责人: Cecil Lewis
• 金额: $ 42.22万
• 依托单位: University of Oklahoma Norman Campus
• 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: 2021-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2045308&HistoricalAwards=false
• 关键词: Hominid; Dental; Metagenomes; Pathogen; Evolution

Dental cavities and periodontal disease, both major oral health problems in today’s world, are caused by opportunistic bacterial pathogens found in the mouth. This project focuses on the evolutionary history of these pathogens, examining how the genomes of oral pathogens differ across a comparative sample of primate species, and, within humans, how they are impacted by changes in dietary practices, geographic space, and time. Through this comparative research and the study of oral pathogen genomes recovered from ancient human populations, this project advances knowledge about pathogen evolution in humans over thousands of years and provides further insight into the relationships between host behavior and pathogen evolution. The project benefits from a team-science approach that involves close collaboration, as well as academic attribution, for descendent communities of the ancient human populations being studied. Project findings are communicated to these communities through public talks focusing on the impact of oral disease, contextualized by microbiome research. The project also contributes to the professional development of researchers through online workshops focusing on ancient microbiome data analysis, supports open science by publication in open-access journals and sharing data through public repositories, and promotes the broader participation of women in STEM through student training and mentoring activities.The transition from a hunter-gatherer to an agricultural lifestyle, as well as the advent of industrialization, are thought to have increased the prevalence of oral disease in humans. However, the way that these transitions affected oral pathogens at a genomic level, especially in terms of their diversity and virulence, have not been fully characterized. Additionally, the broader primate comparative context of oral pathogen diversity is not well understood. In this project, the investigators reconstruct oral pathogen genomes from dental calculus, a calcified form of dental plaque. Dental calculus is known to preserve biomolecules for thousands of years and provides a wealth of information regarding the host, oral bacteria, and diet. Calculus samples are collected from museum specimens of nonhuman primates (chimpanzees, gorillas, and orangutans), and from ancient human populations from the continents of Africa and the Americas. From both continents, samples are retrieved from the same geographic location but from time periods associated with different dietary strategies (hunter-gatherer versus agriculture). The investigators use state-of-the-art ancient DNA protocols, metagenomic sequencing, and target enrichment strategies to generate high-quality genome data for oral pathogens found in these samples. These genome data provide a nuanced understanding of the evolutionary relationships between oral pathogen strains affecting different host species, and how oral pathogen strain diversity and genomic architecture have changed over time and space.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.

牙齿腔和牙周疾病都是当今世界的主要口腔健康问题，都是由口腔中发现的机会性细菌病原体引起的。该项目着重于这些病原体的进化史，研究了在灵长类动物的比较样本中口腔病原体的基因组如何不同，在人类中，它们如何受到饮食实践，地理空间和时间的变化的影响。通过这项比较研究和对从古代人群中恢复的口腔病原体基因组的研究，该项目在数千年的时间内提高了有关人类病原体进化的知识，并进一步深入了解了宿主行为与病原体演变之间的关系。该项目受益于团队科学的方法，该方法涉及与正在研究的古代人口的后代社区进行密切合作以及学术属性。通过关注口腔疾病影响的公开谈判将项目发现传达给这些社区，这是通过微生物组研究的背景方式传达的。该项目还通过关注古代微生物组数据分析的在线研讨会来为研究人员的专业发展做出了贡献人类疾病。但是，这些过渡影响基因组水平的口腔病原体的方式，尤其是在其多样性和病毒方面，尚未得到充分表征。此外，口腔病原体多样性的更广泛的灵长类动物比较背景尚不清楚。在这个项目中，研究人员从牙科牙菌斑的牙齿结石中重建口腔病原体基因组。已知牙科微积分可以保留数千年的生物分子，并提供有关宿主，口服细菌和饮食的大量信息。微积分样品是从非人类灵长类动物（黑猩猩，大猩猩和猩猩）的博物馆标本中收集的，以及来自非洲和美洲延续的古代人口。从这两个大洲都从相同的地理位置中检索样品，但从与不同的饮食策略（猎人 - 采集者与农业）相关的时间段。研究人员使用最先进的古代DNA方案，元基因组测序和靶富集策略来生成这些样品中发现的口腔病原体的高质量基因组数据。这些基因组数据提供了对影响不同宿主物种的口腔病原体菌株之间的进化关系的细微理解，以及口腔病原体菌株多样性和基因组结构如何随时间和空间发生变化。该奖项反映了NSF的法定任务，并被认为是通过使用基金会的智力和更广泛的影响来审查Criteria通过评估来通过评估来获得支持的珍贵的。