Abstract: Thirty years after Susumu Ohno proposed that vertebrate genomes are degenerate polyploids, the extent to which genome duplication contributed to the evolution of the vertebrate genome, if at all, is still uncertain. Sequence-level studies on model organisms whose genomes show clearer evidence of ancient polyploidy are invaluable because they indicate what the evolutionary products of genome duplication can look like. The greatest mystery is the molecular basis of diploidization, the evolutionary process by which a polyploid genome turns into a diploid one.