In his seminal work “On the Origin of Species”, Darwin presented overwhelming evidence for two fundamental phenomena. First, species adapt; and second, new species arise from existing species. A combination of these two processes provides a natural explanation for the origins of the staggering diversity of life. While Darwin explained the first phenomenon – adaptation – through the elegant mechanism of natural selection, he could find no satisfactory explanation to the second phenomenon – speciation – and termed it the “mystery of mysteries”. This “mystery of mysteries” continues to be one of the most important and unsolved problems in biological research over the past 150 years: How do two species evolve from one? The Phadnis Laboratory takes a multi-disciplinary approach combining genetics, genomics and cell biology to address this “mystery of mysteries” and to understand the evolutionary forces that shape the structures of genomes.