Detection and analysis of ancient segmental duplications in mammalian genomes
Abstract
Although segmental duplications (SDs) represent the hotbeds for genomic rearrangements and emergence of new genes, there is still no easy-to-use tools for identifying SDs. Moreover, while most previous studies focused on recently emerged SDs, detection of ancient SDs remains an open problem. We developed an SDquest algorithm for SD finding and applied it to analyzing SDs in human, gorilla, and mouse genomes. Our results demonstrate that previous studies missed many SDs in these genomes and show that SDs account for at least 6.05% of the human genome (version hg19), a 17% increase as compared to the previous estimate. Moreover, SDquest classified 6.42% of the latest GRCh38 version of the human genome as SDs, a large increase as compared to previous studies. We thus propose to re-evaluate evolution of SDs based on their accurate representation across multiple genomes. Towards this goal, we analyzed complex mosaic structure of SDs and decomposed mosaic SDs into elementary SDs, a prerequisite for follow-up evolutionary analysis. We also introduced the concept of the breakpoint graph of mosaic SDs that revealed SD hotspots and suggested that some SDs may have originated from circular extra-chromosomal DNA (ecDNA), not unlike ecDNA that contributes to accelerated evolution in cancer.
- Received August 7, 2017.
- Accepted April 26, 2018.
- Published by Cold Spring Harbor Laboratory Press
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