Armengol Lluis, Pujana Miguel Angel, Cheung Joseph, Scherer Stephen W, Estivill Xavier
Program in Genes and Disease, Center for Genomic Regulation (CRG), Barcelona Biomedical Research Park, Passeig Marítim 37-49, 08003 Barcelona, Catalonia, Spain.
Hum Mol Genet. 2003 Sep 1;12(17):2201-8. doi: 10.1093/hmg/ddg223. Epub 2003 Jul 8.
The sequence of the mouse genome allows one to compare the conservation of synteny between the human and mouse genome and exploration of regions that might have been involved in major rearrangements during the evolution of these two species (evolutionary genome rearrangements). Recent segmental duplications (or duplicons) are paralogous DNA sequences with high sequence identity that account for about 3.5-5% of the human genome and have emerged during the past approximately 35 million years of evolution. These regions are susceptible to illegitimate recombination leading to rearrangements that result in genomic disorders or genomic mutations. A catalogue of several hundred segmental duplications potentially leading to genomic rearrangements has been reported. The authors and others have observed that some chromosome regions involved in genomic disorders are shuffled in orientation and order in the mouse genome and that regions flanked by segmental duplications are often polymorphic. We have compared the human and mouse genome sequences and demonstrate here that recent segmental duplications correlate with breaks of synteny between these two species. We also observed that nine primary regions involved in human genomic disorders show changes in the order or the orientation of mouse/human synteny segments, were often flanked by segmental duplications in the human sequence. We found that 53% of all evolutionary rearrangement breakpoints associate with segmental duplications, as compared with 18% expected in a random location of breaks along the chromosome (P<0.0001). Our data suggest that segmental duplications have participated in the recent evolution of the human genome, as driving forces for evolutionary rearrangements, chromosome structure polymorphisms and genomic disorders.
小鼠基因组序列使人们能够比较人类和小鼠基因组之间的同线性保守性，并探索在这两个物种进化过程中可能参与重大重排的区域（进化基因组重排）。近期的节段性重复（或重复子）是具有高序列同一性的旁系同源DNA序列，约占人类基因组的3.5 - 5%，并且是在过去约3500万年的进化过程中出现的。这些区域易发生异常重组，导致重排，进而引发基因组疾病或基因组突变。已经报道了一份可能导致基因组重排的数百个节段性重复的目录。作者和其他人观察到，一些参与基因组疾病的染色体区域在小鼠基因组中的方向和顺序被打乱，并且节段性重复侧翼的区域通常具有多态性。我们比较了人类和小鼠的基因组序列，并在此证明近期的节段性重复与这两个物种之间的同线性断裂相关。我们还观察到，涉及人类基因组疾病的九个主要区域显示小鼠/人类同线性片段的顺序或方向发生了变化，这些区域在人类序列中常常侧翼是节段性重复。我们发现，所有进化重排断点中有53%与节段性重复相关，而在染色体上随机分布的断点预期比例为18%（P<0.0001）。我们的数据表明，节段性重复作为进化重排、染色体结构多态性和基因组疾病的驱动力，参与了人类基因组的近期进化。
