| Organization, evolution and function of alpha satellite DNA at human centromeres (2005) | |||||||||||||
Abstract | |||||||||||||
| The centromere is a specialized locus responsible for ensuring proper chromosome segregation at mitosis and meiosis. Human centromeres are comprised of large arrays of a primate-specific repeat known as alpha satellite DNA. Understanding the organization and evolution of alpha satellite is essential to delineate the requirements for centromere function. The basic unit of alpha satellite is an ~ 171 bp monomer, and monomers may be organized in one of two types of structure. Higher-order alpha satellite is made up of monomers arranged in homogeneous multimeric higher-order repeat units. In contrast, more divergent monomeric alpha satellite lacks any higher-order periodicity. We have analyzed the alpha satellite in the human genome assembly (Build 34, July 2003), and found regions of both higher-order and monomeric alpha satellite. Although previously identified at all human centromeres, higher-order alpha satellite has only been included in the assemblies of eleven chromosomes. Monomeric alpha satellite typically lies at the edges of larger higher-order arrays, and has been included in all but three chromosome assemblies. The organization of alpha satellite in the human genome is a product of concerted evolutionary processes. We have analyzed the relationships between alpha satellite monomers from multiple chromosomes to discern the exchange mechanisms that have shaped the arrangement of alpha satellite in the genome. Like higher-order alpha satellite described previously, monomeric alpha satellite has a higher frequency of intrachromosomal exchange than interchromosomal exchange. However, comparing orthologous regions of human and chimpanzee alpha satellite, we find that monomeric alpha satellite is more conserved than higher-order alpha satellite. In addition to varying in sequence organization and evolutionary history, monomeric and higher-order alpha satellites also differ in their functionality. Using extended chromosome methods to achieve greater resolution, we have found that antibodies to centromeric proteins only colocalize with higher-order and not monomeric alpha satellite. We have also created artificial chromosomes with de novo centromeres from D17Z1 and DXZ1 higher-order alpha satellites, while other studies have shown that monomeric alpha satellite lacks this functional capacity. This work elucidates the genomic and functional differences between higher-order and monomeric alpha satellite to further define the complex human centromere. | |||||||||||||
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Cited publications (69) | |||||||||||||