Doctoral Dissertation Research: Exploring the Origins of Malaria Using Ancient DNA

人类是由许多生物和文化过程塑造的，包括我们几千年来经历的传染病以及我们对这些事件的反应。鉴于新兴传染病的持续威胁，了解过去人类和病原体相互影响的方式可以为当前的传染病研究提供信息。这个博士论文项目检查的起源和进化的疾病病原体负责最致命的形式的人类疟疾（恶性疟原虫）。这种病原体被认为是通过大猩猩寄生虫向人类的转移而进化的，但这一事件的时间和人类学背景以及疟疾随后的全球传播仍然知之甚少。该项目通过分析古代恶性疟原虫基因组和相关的类人猿寄生虫来追溯疟疾的进化史。该项目还产生可以应用于其他基因组研究项目的新方法和工具，促进学生培训和国际研究合作，并为公共科学教育和推广产生新的资源。该项目是遗传学家和灵长类动物学家国际合作努力的一部分，旨在重建古代恶性疟原虫和相关类人猿寄生虫的基因组。利用基因组分析来估计恶性疟原虫首次作为人类寄生虫出现的时间，联合pi及其同事探索了特定的生态和/或文化因素，特别是农业的采用或多样化，是否可能有利于这种人畜共患病事件。通过比较古代和现代寄生虫基因组，研究人员探索了疟疾全球传播的时间和途径，以了解过去人类流动对病原体传播的影响。该项目预计将为更广泛的科学界提供有价值的、具体的资源，包括古代恶性疟原虫和野生大猩猩疟原虫的全基因组数据。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。

The human species has been shaped by many biological and cultural processes, including the infectious diseases we have experienced over the millennia and our responses to those events. Given the ongoing threat of emerging infectious disease, understanding the ways in which humans and pathogens impacted one another in the past can inform infectious disease research in the present. This doctoral dissertation project examines the origins and evolution of the disease pathogen responsible for the deadliest form of human malaria (P. falciparum). This pathogen is thought to have evolved through the transfer of a gorilla parasite to humans, but the timing and anthropological context for this event and malaria’s subsequent global spread remain poorly understood. The project traces malaria’s evolutionary history through analysis of both ancient P. falciparum genomes and related great ape parasites. The project also generates new methods and tools that can be applied in other genomic research projects, fosters student training and international research collaborations, and generates new resources for public science education and outreach. The project is part of an international collaborative effort of geneticists and primatologists to reconstruct genomes from ancient Plasmodium falciparum and related great ape parasites. Using genomic analyses to estimate when P. falciparum first emerged as a human parasite, the co-PI and colleagues explore whether specific ecological and/or cultural factors, particularly the adoption or diversification of agriculture, may have favored this zoonotic event. Comparing ancient and modern parasite genomes, the investigators explore the timing and route of malaria’s global dissemination to understand the impact of human mobility on pathogen dispersal in the past. This project is anticipated to generate valuable, concrete resources for the broader scientific community, including genome-wide data from ancient Plasmodium falciparum and wild-living gorilla Plasmodium parasites.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.