She Xinwei, Horvath Julie E, Jiang Zhaoshi, Liu Ge, Furey Terrence S, Christ Laurie, Clark Royden, Graves Tina, Gulden Cassy L, Alkan Can, Bailey Jeff A, Sahinalp Cenk, Rocchi Mariano, Haussler David, Wilson Richard K, Miller Webb, Schwartz Stuart, Eichler Evan E
Department of Genetics, Center for Computational Genomics and the Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA.
Nature. 2004 Aug 19;430(7002):857-64. doi: 10.1038/nature02806.
An understanding of how centromeric transition regions are organized is a critical aspect of chromosome structure and function; however, the sequence context of these regions has been difficult to resolve on the basis of the draft genome sequence. We present a detailed analysis of the structure and assembly of all human pericentromeric regions (5 megabases). Most chromosome arms (35 out of 43) show a gradient of dwindling transcriptional diversity accompanied by an increasing number of interchromosomal duplications in proximity to the centromere. At least 30% of the centromeric transition region structure originates from euchromatic gene-containing segments of DNA that were duplicatively transposed towards pericentromeric regions at a rate of six-seven events per million years during primate evolution. This process has led to the formation of a minimum of 28 new transcripts by exon exaptation and exon shuffling, many of which are primarily expressed in the testis. The distribution of these duplicated segments is nonrandom among pericentromeric regions, suggesting that some regions have served as preferential acceptors of euchromatic DNA.
了解着丝粒过渡区域的组织方式是染色体结构和功能的关键方面；然而，基于基因组草图序列很难解析这些区域的序列背景。我们对所有人类着丝粒周围区域（5兆碱基）的结构和组装进行了详细分析。大多数染色体臂（43条中的35条）显示出转录多样性逐渐减少的梯度，同时在靠近着丝粒的区域染色体间重复数量增加。至少30%的着丝粒过渡区域结构起源于富含常染色质基因的DNA片段，这些片段在灵长类动物进化过程中以每百万年6 - 7次的速率向着丝粒周围区域进行重复转座。这一过程通过外显子捕获和外显子重排导致至少28种新转录本的形成，其中许多主要在睾丸中表达。这些重复片段在着丝粒周围区域的分布并非随机，这表明一些区域是常染色质DNA的优先接受者。
