The shared evolutionary capacities of plasmids and extrachromosomal DNA

Our understanding of evolutionary genetics is based largely on chromosomes, but many organisms harbour extrachromosomal forms of DNA that exist in multiple copies per cell and segregate unequally on division. These alternative carriers of genetic information possess unique evolutionary capacities. Recent research on high-copy bacterial plasmids has established important principles about their role in gene amplification, increased mutational supply and the balance between selection and segregational drift. In human cancer, many tumours contain molecules known as extrachromosomal DNA (ecDNA) that exhibit strikingly similar dynamics. From an evolutionary perspective, cancer resembles a unicellular organism under strong selective pressure; because asymmetric segregation of ecDNA produces population-level heterogeneity, ecDNA can fulfil a similar evolutionary role to that of plasmids in bacteria. The analogy between plasmids and ecDNA has been noted previously but not explored in depth. Here, we compare their formation, expression, segregation and evolution, elucidate common principles that apply across both, and identify open questions. We propose that both plasmids and ecDNA function as 'contingency loci' that permit rapid adaptation. Despite important differences, we argue that these extrachromosomal genetic elements can be viewed as an example of convergent evolution.