Did circular DNA shape the evolution of mammalian genomes?

Extrachromosomal circular DNA of chromosomal origin (eccDNA) can rapidly shape the evolution and adaptation of mitotically dividing cells such as tumor cells. However, whether eccDNA has a permanent impact on genome evolution through the germline is largely unexplored. Here, we propose that a large fraction of the syntenic changes that are found between mammalian species are caused by germline transposition of eccDNA. We have previously shown the existence of eccDNA in mammalian meiotic cells. By reanalysis of available synteny maps, we now find that up to 6% of mammalian genomes might have rearranged via a circular DNA intermediate. Hence, eccDNA in the germline is expected to have large effects on evolution of gene order. Highlights Extrachromosomal circular DNA (eccDNA) is present in mammalian germline cells showing that eccDNAs are not excluded, repressed or eliminated during meiosis Large eccDNA reinsertions into the genome can change gene synteny in a recognizable pattern based on its circular junction and integration breakpoint. By reanalyzing synteny maps form 8 mammalian species, we show that 6% of genome of the ungulates cow and sheep can be explained by eccDNA insertions. We propose that reinsertion of large eccDNA that are fixed in germline cells may have contributed to speciation barriers and evolution of new species