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PLoS Comput Biol. 2007 Nov;3(11):e209. Epub 2007 Sep 14.

Are there rearrangement hotspots in the human genome?

Author information

  • 1Department of Computer Science and Engineering, University of California San Diego, San Diego, California, United States of America. maxal@cs.ucsd.edu

Abstract

In a landmark paper, Nadeau and Taylor [18] formulated the random breakage model (RBM) of chromosome evolution that postulates that there are no rearrangement hotspots in the human genome. In the next two decades, numerous studies with progressively increasing levels of resolution made RBM the de facto theory of chromosome evolution. Despite the fact that RBM had prophetic prediction power, it was recently refuted by Pevzner and Tesler [4], who introduced the fragile breakage model (FBM), postulating that the human genome is a mosaic of solid regions (with low propensity for rearrangements) and fragile regions (rearrangement hotspots). However, the rebuttal of RBM caused a controversy and led to a split among researchers studying genome evolution. In particular, it remains unclear whether some complex rearrangements (e.g., transpositions) can create an appearance of rearrangement hotspots. We contribute to the ongoing debate by analyzing multi-break rearrangements that break a genome into multiple fragments and further glue them together in a new order. In particular, we demonstrate that (1) even if transpositions were a dominant force in mammalian evolution, the arguments in favor of FBM still stand, and (2) the "gene deletion" argument against FBM is flawed.

PMID:
17997591
[PubMed - indexed for MEDLINE]
PMCID:
PMC2065889
Free PMC Article

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