The generation, maintenance, and function of extrachromosomal DNA in a divergent eukaryote

Extrachromosomal DNA (ecDNA) is DNA that exists and functions separately from the main genome. In the malaria parasite, ecDNA is circular, unlike the linear chromosomes. Some ecDNAs encode instructions that confer new abilities such as resistance to a drug.

They mutate over time, conferring newfound functions, and can eventually rejoin the main chromosome. This project will study this DNA form in a single cell organism to better understand how it arises and changes to confer new abilities. The Broader Impact of the work includes intrinsic biological discoveries in a group of organisms that cause a range of diseases such as malaria.

Additional activities seek to improve scientific and technical literacy by building virtual reality (VR) skills in the future workforce.

This research will generate a comprehensive framework to study extrachromosomal ecDNA (ecDNA). The generation, maintenance, and replication of these molecules vary across different organisms, making the integration of information from diverse contexts challenging. Studies in this proposal bring together a range of cutting-edge microscopy, molecular genomics, and computational techniques to study the complete lifecycle of ecDNA in the Plasmodium protozoan.

Research activities will take advantage of exceptional aspects of Plasmodium biology to gain key insights into the purpose and lifecycle of ecDNA. Studies will specifically evaluate: 1) the connection between chromosomal genes and ecDNA, 2) the propensity for ecDNA diversity, 3) the contribution of cellular pathways and sequences to ecDNA generation and stability, and 4) the clustering of ecDNA within the nucleus.

Results from the project will contribute to knowledge about ecDNA structure and frequency and how genome characteristics directly impact adaptive potential. Novel approaches and concepts will inspire new insight into ecDNA biology across diverse organisms.

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.