美国加州大学圣地亚哥分校的研究人员就人类基因组重组提出了一项新理论。他们研究的结果发表在11月9日的《PLoS计算生物学》（PLoS Computational Biology）杂志上，研究支持了人类基因组中确实存在重组热点的理论。
Max Alekseyev和Pavel Pevzner博士发展了一种分析复杂重组（包括易位transpositions）的理论，该理论证实及时易位是一种主要的进化力量，哺乳动物基因组中仍然存在重组热点。
二十世纪七十年代，Susumo Ohno提出了随机缺损模型（RBM，random breakage model），之后Nadeau和Taylor在1984年正式将其上升为假说。这个模型假定重组是随机的，并且在哺乳动物基因组中没有重组热点。大部分生物学家都相信这个模型具有预测能力。
然而，到了2003年，这个模型被Pevzner和Tesler推翻，他们提出了一种替代的染色体进化“脆性缺损模型”（FBM，fragile breakage model）。FBM推测，人类基因组是一种由难发生重组的固化区域和容易发生重组的脆性区域构成的镶嵌体。
近期大部分研究都指出了“存在重组热点区域”的理论，一些研究人员仍然支持RBM模型。这项新的研究则是重组热点问题争议的一个重要进展。
原始出处:
PLoS Computational Biology
Are There Rearrangement Hotspots in the Human Genome?
Max Alekseyev1¤, Pavel A. Pevzner1
1 UCSD, United States of America
In a landmark paper, Nadeau and Taylor (Nadeau J.H. and Taylor B.A. (1984). Proceedings of the National Academy of Sciences 81: 814-818) 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 mapping and sequencing 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 (Pevzner P. and Tesler G. (2003) Proceedings of the National Academy of Sciences 100: 7672-7677) who introduced the Fragile Breakage Model (FBM) postulating that the human genome is a mosaic 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. While multi-break rearrangements were studied in depth for k=2 breaks, the k-break rearrangement distance problem for an arbitrary k remains unsolved. We prove a theorem for computing multi-break rearrangement distance and use it to resolve the ``FBM versus RBM' controversy. In particular, we demonstrate that (i) even if transpositions were a dominant force in mammalian evolution, the arguments in favor of FBM still stand and (ii) the ``gene deletion' argument against FBM is flawed.
Editor: Daniel Huson, Tübingen University, Center for Bioinformatics Tübingen, Tübingen, Germany
Citation: Alekseyev M, Pevzner PA (2007) Are There Rearrangement Hotspots in the Human Genome? PLoS Comput Biol. In press. doi:10.1371/journal.pcbi.0030209.eor
Received: February 14, 2007; Accepted: September 13, 2007
Copyright: © 2007 Alekseyev and Pevzner. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
¤ To whom correspondence should be addressed. E-mail: maxal@cs.ucsd.edu
