Duplication with structural modification through extrachromosomal circular and lariat DNA in the human genome

Duplication plays an important role in creating drastic changes in genome evolution. In addition to well-known tandem duplication, duplication can occur such that a duplicated DNA fragment is inserted at another location in the genome. Here, we report several genomic regions in the human genome that could be best explained by two types of insertion-based duplication mechanisms, where a duplicated DNA fragment was modified structurally and then inserted into the genome. In one process, the DNA fragment is turned into an extrachromosomal circular DNA, cut somewhere in the circle, and reintegrated into another location in the genome. And in the other, the DNA fragment forms a “lariat structure” with a “knot”, the strand is swapped at the knot, and is then reintegrated into the genome. Our results suggest that insertion-based duplication may not be a simple process; it may involve a complicated procedures such as structural modification before reintegration. However, the molecular mechanism has yet to be fully understood.