Extrachromosomal Circular DNA: A Mobile Genetic Element Shaping Host Biology.

Abstract

DNA carries genetic information, ensuring the stable transmission of genetic material through generations. However, DNA sequences can be constantly rewritten, allowing evolution and adaptation to occur at both the cellular and species levels. To facilitate this dynamic process, the genome is enriched with mobile genetic elements that can move within DNA sequences. While transposable elements are the classic example of mobile DNA, we propose that extrachromosomal circular DNA (ecDNA) represents another class of mobile genetic elements. This class can also introduce a new layer of genome dynamics, significantly shaping host biology. This review traces the historical discoveries and conceptual evolution of ecDNA, categorizing its diverse forms across organisms and highlighting its life cycle from biogenesis to maintenance and clearance. We discuss ecDNA's pivotal roles in physiological processes, including development, stress adaptation, and species evolution, and emphasize its pathological significance in cancer progression, drug resistance, and viral infections. Finally, we explore therapeutic strategies targeting ecDNA biology, offering a framework for translational advances in oncology and antiviral treatment. Together, these insights position ecDNA as a critical force in shaping genome dynamics and as a promising target for future biomedical interventions.