Human NORs, comprising rDNA arrays and functionally conserved distal elements, are located within dynamic chromosomal...

Area of Science:

• Genomics
• Human Genetics
• Molecular Biology

Background:

• Nucleolar organizer regions (NORs) containing ribosomal DNA (rDNA) are on acrocentric chromosome p-arms, but their absence in genome references hinders research.
• A previously identified distal junction (DJ) DNA sequence abuts rDNA arrays, is shared among acrocentrics, and influences nucleolar organization.

Purpose of the Study:

• To sequence the DJ from all human acrocentric chromosomes, including multiple HSA21 versions, to enable their inclusion in genome references.
• To analyze DJ sequence and functional conservation across human acrocentrics and compare with chimpanzee acrocentrics.

Main Methods:

• Sequencing of the DJ region from human acrocentric chromosomes using monochromosomal somatic cell hybrids.
• Comparative sequence analysis of DJ and rDNA arrays in humans and chimpanzees.

Main Results:

• Approximately 3 Mb of novel sequence was obtained for the DJ from all acrocentric chromosomes.
• Remarkable sequence and functional conservation of the DJ was observed among human acrocentrics.
• DJ-like sequences and rDNA arrays are inverted as a unit in chimpanzees compared to humans, indicating a conserved functional locus.

Conclusions:

• Direct evidence for exchanges between heterologous human acrocentric p-arms and extensive structural variation was found.
• The molecular definition of NORs requires reevaluation based on these findings.
• Novel genomic structural variation and a rationale for NOR chromosomal organization were uncovered.