The last common ancestor of humans and rodents lived more than 80 million years ago, and billions of changes in their respective DNA sequences have occurred over this vast timespan. Yet, intriguingly, there are a few hundred stretches of DNA in our genome that are still identical to the corresponding sequences in mice and rats. Generally, sequence conservation between distantly related species is an indication that the function the DNA serves is vitally important and highly sensitive to mutations. For example, most DNA sequences that encode proteins show at least moderate conservation in evolution. However, more than two-thirds of the “ultraconserved” sequences shared by humans and rodents are outside of protein-coding genes, raising the question of what led to their extreme level of conservation.