Hominid Dental Metagenomes for Pathogen Evolution Research

蛀牙和牙周病是当今世界两大口腔健康问题，都是由口腔内的机会性细菌病原体引起的。该项目侧重于这些病原体的进化史，研究在灵长类物种的比较样本中口腔病原体基因组的差异，以及在人类中，它们如何受到饮食习惯、地理空间和时间变化的影响。通过这项比较研究和从古代人群中恢复的口腔病原体基因组的研究，该项目推进了数千年来人类病原体进化的知识，并进一步深入了解宿主行为与病原体进化之间的关系。该项目受益于团队科学方法，该方法涉及密切合作，以及学术归属，用于研究古代人口的后裔社区。通过以微生物组研究为背景，着重于口腔疾病影响的公开讲座，将项目发现传达给这些社区。该项目还通过关注古代微生物组数据分析的在线研讨会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存储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。从狩猎采集者到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，特别是在其多样性和毒性方面，尚未得到充分表征。此外，更广泛的灵长类动物口腔病原体多样性的比较背景还没有得到很好的理解。在这个项目中，研究人员从牙结石（一种钙化的牙菌斑）中重建口腔病原体基因组。众所周知，牙石可以保存数千年的生物分子，并提供有关宿主、口腔细菌和饮食的丰富信息。微积分样本来自博物馆的非人类灵长类动物（黑猩猩、大猩猩和猩猩）标本，以及来自非洲和美洲大陆的古代人类种群。在这两个大洲，样本是从相同的地理位置采集的，但来自与不同饮食策略相关的时期（狩猎采集者与农业）。研究人员使用最先进的古代DNA协议、宏基因组测序和目标富集策略，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。这些基因组数据提供了对影响不同宿主物种的口腔病原体菌株之间进化关系的细致理解，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变化。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。

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.