Genome Rearrangements
with Son Pham

In the late 1980s, Jeffrey Palmer and his colleagues discovered a remarkable and novel pattern of evolutionary change in plant organelles. They compared the mitochondrial genomes of cabbage and turnip, which are very closely related (many genes are 99% identical). To their surprise, these molecules, which are almost identical in gene sequences, differ dramatically in two order. This discovery and many other studies in the last decades convincingly proved that genome rearrangements represent a common mode of molecular evolution.

Every study of genome rearrangements involves solving a combinatorial "puzzle" to find a series of rearrangements that transform one genome into another. We are trying to reconstruct rearrangements and to reveal the ancestral mammalian genome achitecture.

Rearrangements are genomic "earthquakes" that change the chromosomal architectures. The fundamental question in molecular evolution is whether there exist "chromosomal faults" (rearrangement hotspots) where rearrangements are happening over and over again. The random breakage model (RBM) postulates that rearrangements are "random," and thus there are no rearrangement hotspots in mammalian genomes. RBM was proposed by Susumo Ohno in 1970 and later was formalized by Nadeau and Taylor in 1984. It was embraced by biologists from the very beginning due to its prophetic prediction power, and only in 2003 was refuted by Pevzner and Tesler, who suggested an alternative fragile breakage model (FBM) of chromosome evolution. We analyze implications of FBM and search for the currently active fragile regions in the human genome.