DNA Circles as Vehicles for Genes to Evade Chromosomal Discipline

In this Perspective article, we follow the journey of a gene that breaks free from its stringent chromosomal transmission dynamics to become an independently multiplying agent on so-called extrachromosomal circular DNA (ecDNA/eccDNA). We discuss how the release of a gene from its chromosomal anchor can affect its dosage, regulatory context, and potential evolutionary trajectory before examining the phenotypic implications for unicellular and multicellular eukaryotes that transmit genes on circular DNA. We also briefly explore the fundamental difference between circularized genes in flowering plants (angiosperms) and mammals (primarily cancer) concerning somatic and germline inheritance.