美國加州大學(xué)圣地亞哥分校的研究人員就人類基因組重組提出了一項新理論。他們研究的結(jié)果發(fā)表在11月9日的《PLoS計算生物學(xué)》（PLoS Computational Biology）雜志上,，研究支持了人類基因組中確實存在重組熱點的理論,。
Max Alekseyev和Pavel Pevzner博士發(fā)展了一種分析復(fù)雜重組（包括易位transpositions）的理論，該理論證實及時易位是一種主要的進(jìn)化力量,，哺乳動物基因組中仍然存在重組熱點,。
二十世紀(jì)七十年代,，Susumo Ohno提出了隨機(jī)缺損模型（RBM，random breakage model）,，之后Nadeau和Taylor在1984年正式將其上升為假說,。這個模型假定重組是隨機(jī)的，并且在哺乳動物基因組中沒有重組熱點,。大部分生物學(xué)家都相信這個模型具有預(yù)測能力,。
然而，到了2003年,，這個模型被Pevzner和Tesler推翻,，他們提出了一種替代的染色體進(jìn)化“脆性缺損模型”（FBM，fragile breakage model）,。FBM推測,，人類基因組是一種由難發(fā)生重組的固化區(qū)域和容易發(fā)生重組的脆性區(qū)域構(gòu)成的鑲嵌體。
近期大部分研究都指出了“存在重組熱點區(qū)域”的理論,，一些研究人員仍然支持RBM模型,。這項新的研究則是重組熱點問題爭議的一個重要進(jìn)展。
原始出處:
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: [email protected]
