The increasing availability of high-quality genome assemblies raised interest in the characterization of genomic architecture. Major architectural elements, such as common repeats and segmental duplications (SDs), increase genome plasticity that stimulates further evolution by changing the genomic structure and inventing new genes. Optimal computation of SDs within a genome requires quadratic-time local alignment algorithms that are impractical due to the size of most genomes. Additionally, to perform evolutionary analysis, one needs to characterize SDs in multiple genomes and find relations between those SDs and unique (non-duplicated) segments in other genomes. A na ̈ıve approach consisting of multiple sequence alignment would make the optimal solution to this problem even more impractical. Thus there is a need for fast and accurate algorithms to characterize SD structure in multiple genome assemblies to better understand the evolutionary forces that shaped the genomes of today. Here we introduce a new approach, BISER, to quickly detect SDs in multiple genomes and identify elementary SDs and core duplicons that drive the formation of such SDs. BISER improves earlier tools by (i) scaling the detection of SDs with low homology (75%) to multiple genomes while introducing further 10–34× speed-ups over the existing tools, and by (ii) characterizing elementary SDs and detecting core duplicons to help trace the evolutionary history of duplications to as far as 300 million years. / Graduate