Genomic and genetic definition of a functional human centromere
Genomic and genetic definition of a functional human centromere
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DOI：
10.1126/science.1065042
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发表时间：
2001-10-05
期刊：
影响因子：
56.9
通讯作者：
Willard, HF
中科院分区：
文献类型：
--
作者：
Schueler, MG;Higgins, AW;Willard, HF
人类染色体着丝粒的定义需要对这些区域有完整的基因组理解。为此，我们报告了物理作图、遗传和功能方法的集成，以及选定区域的测序，以确定人类X染色体的着丝粒，并探索负责染色体分离的序列的进化。X短臂上的表达序列与染色体特异的α卫星阵列DXZ1之间的过渡区跨度约为450kb，卫星丰富。在这个卫星区域和典型的DXZ1重复序列之间的交界处，发散的重复单元提供了不相等交叉的直接证据，作为这些阵列的均质力。有丝分裂稳定的染色体重排的缺失分析和人类人工染色体检测的结果表明，DXZ1 DNA足以满足着丝粒功能。进化研究表明，存在于X染色体着丝粒周围的白色α卫星DNA似乎是祖先灵长类着丝粒的后代，目前基于DXZ1序列的功能着丝粒是该卫星DNA最近协同进化的产物。
The definition of centromeres of human chromosomes requires a complete genomic understanding of these regions. Toward this end, we report integration of physical mapping, genetic, and functional approaches, together with sequencing of selected regions, to define the centromere of the human X chromosome and to explore the evolution of sequences responsible for chromosome segregation. The transitional region between expressed sequences on the short arm of the X and the chromosome-specific alpha satellite array DXZ1 spans about 450 kilobases and is satellite-rich. At the junction between this satellite region and canonical DXZ1 repeats, diverged repeat units provide direct evidence of unequal crossover as the homogenizing force of these arrays. Results from deletion analysis of mitotically stable chromosome rearrangements and from a human artificial chromosome assay demonstrate that DXZ1 DNA is sufficient for centromere function. Evolutionary studies indicate that, white alpha satellite DNA present throughout the pericentromeric region of the X chromosome appears to be a descendant of an ancestral primate centromere, the current functional centromere based on DXZ1 sequences is the product of the much more recent concerted evolution of this satellite DNA.