Circular DNA intermediates in the generation of large human segmental duplications
Javier U. Chicote,
Marcos López-Sánchez,
Tomàs Marquès-Bonet,
José Callizo,
Luis A. Pérez-Jurado,
Antonio García-España
Affiliations
Javier U. Chicote
Research Unit, Hospital Universitari de Tarragona Joan XXIII, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili
Marcos López-Sánchez
Genetics Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Tomàs Marquès-Bonet
Institut de Biologia Evolutiva (CSIC-UPF), Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
José Callizo
Department of Ophthalmology, Hospital Universitari de Tarragona Joan XXIII, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili
Luis A. Pérez-Jurado
Genetics Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra
Antonio García-España
Research Unit, Hospital Universitari de Tarragona Joan XXIII, Institut d’Investigació Sanitària Pere Virgili, Universitat Rovira i Virgili
Abstract Background 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. Results 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. Conclusions 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.
