Regulated Formation of Extrachromosomal Circular DNA Molecules during Development in Xenopus laevis

Abstract

Extrachromosomal circular DNA molecules of chromosomal origin have been detected in many organisms and are thought to reflect genomic plasticity in eukaryotic cells. Here we report a developmentally regulated formation of extrachromosomal circular DNA that occurs de novo in preblastula Xenopus embryos. This specific DNA population is not detected in the male or female germ cells and is dramatically reduced in later developmental stages and in adult tissues. The activity responsible for the de novo production of extrachromosomal circles is maternally inherited, is stored in the unfertilized egg, and requires genomic DNA as a template. The formation of circular molecules does not require genomic DNA replication but both processes can occur simultaneously in the early development. The production of extrachromosomal circular DNA does not proceed at random since multimers of the tandemly repeated sequence satellite 1 were over-represented in the circle population, while other sequences (such as ribosomal DNA and JCC31 repeated sequence) were not detected. This phenomenon reveals an unexpected plasticity of the embryonic genome which is restricted to the early developmental stage.

ACKNOWLEDGMENTS

We thank P. Brooks for a critical reading of the manuscript.

This study was supported by grants from the CNRS, the Association pour la Recherche sur le Cancer, the Ligue Nationale contre le Cancer, and the Fondation pour la Recherche Médicale. S.C. was supported by postdoctoral fellowships from the European Molecular Biology Organization and the Fondation pour la Recherche Médicale.