Circular DNA intermediates in the generation of large human segmental duplications

Duplications of large genomic segments provide genetic diversity in genome evolution. Despite their importance, how these duplications are generated remains uncertain, particularly for distant duplicated genomic segments.

Here we provide evidence of the participation of circular DNA intermediates in the single generation of some large human segmental duplications. A specific reversion of sequence order from A-B/C-D to B-A/D-C between duplicated segments and the presence of only microhomologies and short indels at the evolutionary breakpoints suggest a circularization of the donor ancestral locus and an accidental replicative interaction with the acceptor locus.

This novel mechanism of random genomic mutation could explain several distant genomic duplications including some of the ones that took place during recent human evolution.