Human nucleolar organizer regions (NORs), containing ribosomal gene (rDNA) arrays, are located on the p-arms of acrocentric chromosomes (HSA13-15, 21, and 22). Absence of these p-arms from genome references has hampered research on nucleolar formation. Previously, we assembled a distal junction (DJ) DNA sequence contig that abuts rDNA arrays on their telomeric side, revealing that it is shared among the acrocentrics and impacts nucleolar organization. To facilitate inclusion into genome references, we describe sequencing the DJ from all acrocentrics, including three versions of HSA21, ∼3 Mb of novel sequence. This was achieved by exploiting monochromosomal somatic cell hybrids containing single human acrocentric chromosomes with NORs that retain functional potential. Analyses revealed remarkable DJ sequence and functional conservation among human acrocentrics. Exploring chimpanzee acrocentrics, we show that "DJ-like" sequences and abutting rDNA arrays are inverted as a unit in comparison to humans. Thus, rDNA arrays and linked DJs represent a conserved functional locus. We provide direct evidence for exchanges between heterologous human acrocentric p-arms, and uncover extensive structural variation between chromosomes and among individuals. These findings lead us to revaluate the molecular definition of NORs, identify novel genomic structural variation, and provide a rationale for the distinctive chromosomal organization of NORs.

中文翻译：

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包含rDNA阵列和功能保守的远端元件的人NOR位于动态染色体区域内。

包含核糖体基因（rDNA）阵列的人核仁组织区（NORs）位于acrocentric染色体（HSA13-15、21和22）的p臂上。基因组参考文献中缺少这些p臂阻碍了对核仁形成的研究。以前，我们组装了一个远端连接（DJ）DNA序列重叠群，在其端粒侧邻接rDNA阵列，揭示了它在顶体中共享并影响核仁组织。为了便于将其纳入基因组参考中，我们描述了对来自所有杂居中心的DJ进行测序的方法，包括三种版本的HSA21，〜3 Mb的新序列。这是通过利用含有单个人acrocentric染色体且具有保留功能潜力的NOR的单染色体体细胞杂交体来实现的。分析表明，在人类杂肢中心中，DJ序列显着且功能保守。探索黑猩猩的近端中心动物，我们发现与人类相比，“ DJ样”序列和邻接的rDNA阵列被倒置为一个单位。因此，rDNA阵列和链接的DJ代表保守的功能基因座。我们提供异种人类acrocentric p臂之间的交换的直接证据，并揭示染色体之间和个体之间广泛的结构变异。这些发现使我们重新评估NOR的分子定义，鉴定新的基因组结构变异，并为NOR的独特染色体组织提供了理论依据。rDNA阵列和链接的DJ代表保守的功能基因座。我们提供异种人类acrocentric p臂之间的交换的直接证据，并揭示染色体之间和个体之间广泛的结构变异。这些发现使我们重新评估NOR的分子定义，鉴定新的基因组结构变异，并为NOR的独特染色体组织提供了理论依据。rDNA阵列和链接的DJ代表保守的功能基因座。我们提供异种人类acrocentric p臂之间的交换的直接证据，并揭示染色体之间和个体之间广泛的结构变异。这些发现使我们重新评估NOR的分子定义，鉴定新的基因组结构变异，并为NOR的独特染色体组织提供了理论依据。