Of Mice and Men

More than 200 major genome rearrangements, and over 3,000 mini-rearrangements. That is roughly what it took for humans and mice to evolve from a common ancestor roughly 75 million years ago. It’s a stunning conclusion reached by two Jacobs School researchers who are playing a key role in an international effort to learn lessons from comparing the human and mouse genomes.

In early December, Nature published a near-complete genetic blueprint of the mouse, and with it, the first comparisons with the human genome. The paper was authored by researchers at more than two dozen universities that are members of the Mouse Genome Sequencing Consortium, including two from UCSD: Computer Science and Engineering Professor Pavel Pevzner, and project scientist Glenn Tesler. The two computational biologists also published a companion paper in January’s Genome Research (in collaboration with Michael Kamal and Eric Lander at the Whitehead/MIT Center for Genome Research), offering more detailed insights about the evolution of mammals.

Pevzner and Tesler developed a new algorithm to differentiate macro- and micro-level genome rearrangements. With it, they analyzed the genomes block by block, finding evidence that genome rearrangements occurred more commonly than previously believed, especially those mini-rearrangements. “The human and mouse genome sequences can be viewed as two decks of cards obtained by re-shuffling from a master deck—an ancestral mammalian genome,” said Pevzner. “And in addition to the major rearrangements that shuffle large chunks of the gene pool, our research confirmed another process that shuffles only small chunks.” Added Tesler: “There were over 3,000 rearrangements of the small chunks within the major blocks—a much higher figure than previously thought.”