Rearrangement Hotspots
by BradfordA PLOS Computational Biology paper entitled Are There Rearrangement Hotspots in the Human Genome? is authored by Max A. Alekseyev and Pavel A. Pevzner. It addresses an issue important to our understanding of genomic dynamics and how we view causes of change. Recent controversy about rearrangement hotspots and different models are discusssed. The random breakage model (RBM) is contrasted with the fragile breakage model (FBM). The former argues that no rearrangement hotspots exist in the human genome while the latter argues that the human genome is a mosaic with regions having low propensity for rearrangements existing along with fragile regions or rearrangement hotspots. The summary of the paper follows:
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. However, the rebuttal of RBM caused a controversy, and in 2004, Sankoff and Trinh gave a rebuttal of the rebuttal of RBM. This led to a split among researchers studying chromosome evolution: while most recent studies support the existence of rearrangement hotspots, others feel that further analysis is needed to resolve the validity of RBM. In this paper, we develop a theory for analyzing complex rearrangements (including transpositions) and demonstrate that even if transpositions were a dominant evolutionary force, there are still rearrangement hotspots in mammalian genomes.
The authors note a very intriguing question namely, if FBM replaces RBM then why do certain regions break while others do not? It is an open question at this point.
