Human NORs, comprising rDNA arrays and functionally conserved distal elements, are located within dynamic chromosomal regions
- Marjolein van Sluis3,
- Michael Ó Gailín3,
- Joseph G.W. McCarter1,3,
- Hazel Mangan,
- Alice Grob2 and
- Brian McStay
- Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland
- Corresponding author: brian.mcstay{at}nuigalway.ie
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↵3 These authors contributed equally to this work.
Abstract
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.
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Footnotes
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.331892.119.
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Freely available online through the Genes & Development Open Access option.
- Received August 19, 2019.
- Accepted October 23, 2019.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.