Alekseyev Max A, Pevzner Pavel A
Department of Computer Science and Engineering, University of California San Diego, San Diego, California, United States of America.
PLoS Comput Biol. 2007 Nov;3(11):e209. doi: 10.1371/journal.pcbi.0030209. Epub 2007 Sep 14.
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.
在一篇具有里程碑意义的论文中，纳多和泰勒[18]提出了染色体进化的随机断裂模型（RBM），该模型假定人类基因组中不存在重排热点。在接下来的二十年里，众多分辨率不断提高的研究使RBM成为染色体进化的实际理论。尽管RBM具有预言性的预测能力，但最近它被佩夫兹纳和特斯勒[4]驳斥，他们引入了脆弱断裂模型（FBM），假定人类基因组是由固体区域（重排倾向低）和脆弱区域（重排热点）组成的镶嵌体。然而，对RBM的反驳引发了一场争论，并导致研究基因组进化的研究人员之间出现了分歧。特别是，目前尚不清楚一些复杂的重排（如转座）是否会造成重排热点的假象。我们通过分析将基因组断裂成多个片段并以新顺序重新拼接在一起的多断点重排，为正在进行的争论做出了贡献。特别是，我们证明：（1）即使转座是哺乳动物进化中的主导力量，支持FBM的论点仍然成立；（2）反对FBM的“基因缺失”论点存在缺陷。
