Hominid Dental Metagenomes for Pathogen Evolution Research

龋齿和牙周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。这个项目的重点是这些病原体的进化史，研究口腔病原体的基因组在灵长类物种的比较样本中有何不同，以及在人类内部，它们如何受到饮食习惯、地理空间和时间变化的影响。通过这种比较研究和对从古人类种群中恢复的口腔病原体基因组的研究，该项目推进了对数千年来人类病原体进化的认识，并进一步深入了解宿主行为和病原体进化之间的关系。该项目得益于团队科学方法，这种方法涉及密切合作，以及对正在研究的古人类后代社区的学术归属。项目结果通过公开演讲传达给这些社区，重点是口腔疾病的影响，并结合微生物组研究。该项目还通过侧重于古代微生物组数据分析的在线讲习班促进研究人员的专业发展，通过在开放获取期刊上发表文章和通过公共储存库共享数据来支持开放科学，并通过学生培训和指导活动促进妇女更广泛地参与STEM。从狩猎采集者向农业生活方式的转变以及工业化的到来被认为增加了人类口腔疾病的患病率。然而，这些转变在基因组水平上影响口腔病原体的方式，特别是在它们的多样性和毒力方面，还没有完全表征。此外，口腔病原体多样性的更广泛的灵长类比较背景还没有被很好地理解。在这个项目中，研究人员从牙结石重建口腔病原体基因组，牙结石是一种钙化形式的牙菌斑。众所周知，牙结石保存了数千年的生物分子，并提供了关于宿主、口腔细菌和饮食的丰富信息。微积分样本来自非人灵长类动物(黑猩猩、大猩猩和猩猩)的博物馆标本，以及来自非洲和美洲大陆的古人类种群。在这两个大陆，样本是从相同的地理位置但从不同的饮食策略(狩猎-采集与农业)相关的时间段提取的。研究人员使用最先进的古代DNA协议、元基因组测序和靶向浓缩策略，为这些样本中发现的口腔病原体生成高质量的基因组数据。这些基因组数据为影响不同宿主物种的口腔病原体菌株之间的进化关系提供了细微的了解，以及口腔病原体菌株多样性和基因组结构如何随着时间和空间的变化而变化。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.