rDNA magnification is a unique feature of germline stem cells

Proc Natl Acad Sci U S A. 2023 Nov 21;120(47):e2314440120. doi: 10.1073/pnas.2314440120. Epub 2023 Nov 15.

Abstract

Ribosomal DNA (rDNA) encodes ribosomal RNA and exists as tandem repeats of hundreds of copies in the eukaryotic genome to meet the high demand of ribosome biogenesis. Tandemly repeated DNA elements are inherently unstable; thus, mechanisms must exist to maintain rDNA copy number (CN), in particular in the germline that continues through generations. A phenomenon called rDNA magnification was discovered over 50 y ago in Drosophila as a process that recovers the rDNA CN on chromosomes that harbor minimal CN. Our recent studies indicated that rDNA magnification is the mechanism to maintain rDNA CN under physiological conditions to counteract spontaneous CN loss that occurs during aging. Our previous studies that explored the mechanism of rDNA magnification implied that asymmetric division of germline stem cells (GSCs) may be particularly suited to achieve rDNA magnification. However, it remains elusive whether GSCs are the unique cell type that undergoes rDNA magnification or differentiating germ cells are also capable of magnification. In this study, we provide empirical evidence that suggests that rDNA magnification operates uniquely in GSCs, but not in differentiating germ cells. We further provide computer simulation that suggests that rDNA magnification is only achievable through asymmetric GSC divisions. We propose that despite known plasticity and transcriptomic similarity between GSCs and differentiating germ cells, GSCs' unique ability to divide asymmetrically serves a critical role of maintaining rDNA CN through generations, supporting germline immortality.

Keywords: Drosophila germline; germline immortality; rDNA copy number maintenance; ribosomal DNA.

MeSH terms

  • Animals
  • Computer Simulation
  • DNA, Ribosomal / genetics
  • DNA, Ribosomal / metabolism
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Drosophila* / genetics
  • Drosophila* / metabolism
  • Germ Cells / metabolism
  • Stem Cells / metabolism

Substances

  • DNA, Ribosomal
  • Drosophila Proteins