scholarly journals Transgenerational dynamics of rDNA copy number in Drosophila male germline stem cells

2017 ◽  
Author(s):  
Kevin L. Lu ◽  
Jonathan O. Nelson ◽  
Natalie Warsinger-Pepe ◽  
Yukiko M. Yamashita
Keyword(s):  
Copy Number ◽  
Replicative Senescence ◽  
Yeast Cells ◽  
Rrna Genes ◽  
Germline Stem Cell ◽  
Genetic Elements ◽  
Male Germline ◽  
Rdna Loci ◽  
Rdna Copy ◽  
Rdna Copy Number

AbstractrDNA loci, composed of hundreds of tandemly duplicated arrays of rRNA genes, are known to be among the most unstable genetic elements due to their repetitive nature. rDNA instability underlies aging (replicative senescence) in yeast cells, however, its contribution to the aging of multicellular organisms is poorly understood. In this study, we investigate the dynamics of rDNA loci during aging in the Drosophila male germline stem cell (GSC) lineage, and show that rDNA copy number decreases during aging. Our study further reveals that this age-dependent decrease in rDNA copy number is heritable from generation to generation, yet GSCs in animals that inherit reduced rDNA copy number are capable of recovering normal rDNA copy number. Based on these findings, we propose that rDNA loci are dynamic genetic elements, where rDNA copy number changes dynamically yet is maintained through a recovery mechanism in the germline.

scholarly journals Transgenerational dynamics of rDNA copy number in Drosophila male germline stem cells

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Kevin L Lu ◽  
Jonathan O Nelson ◽  
George J Watase ◽  
Natalie Warsinger-Pepe ◽  
Yukiko M Yamashita
Keyword(s):  
Copy Number ◽  
Replicative Senescence ◽  
Yeast Cells ◽  
Rrna Genes ◽  
Germline Stem Cell ◽  
Genetic Elements ◽  
Male Germline ◽  
Rdna Loci ◽  
Rdna Copy ◽  
Rdna Copy Number

rDNA loci, composed of hundreds of tandemly duplicated arrays of rRNA genes, are known to be among the most unstable genetic elements due to their repetitive nature. rDNA instability underlies aging (replicative senescence) in yeast cells, however, its contribution to the aging of multicellular organisms is poorly understood. In this study, we investigate the dynamics of rDNA loci during aging in the Drosophila male germline stem cell (GSC) lineage, and show that rDNA copy number decreases during aging. Our study further reveals that this age-dependent decrease in rDNA copy number is heritable from generation to generation, yet GSCs in young animals that inherited reduced rDNA copy number are capable of recovering normal rDNA copy number. Based on these findings, we propose that rDNA loci are dynamic genetic elements, where rDNA copy number changes dynamically yet is maintained through a recovery mechanism in the germline.

scholarly journals Gene dosage compensation of rRNA transcript levels in Arabidopsis thaliana lines with reduced ribosomal gene copy number

2021 ◽  
Author(s):  
Francesca B Lopez ◽  
Antoine Fort ◽  
Luca Tadini ◽  
Aline V Probst ◽  
Marcus McHale ◽  
...  
Keyword(s):  
Arabidopsis Thaliana ◽  
Genome Editing ◽  
Dosage Compensation ◽  
Copy Number ◽  
Gene Dosage ◽  
Rrna Genes ◽  
Gene Copy ◽  
Transcript Levels ◽  
Rdna Copy ◽  
Rdna Copy Number

Abstract The 45S rRNA genes (rDNA) are amongst the largest repetitive elements in eukaryotic genomes. rDNA consists of tandem arrays of rRNA genes, many of which are transcriptionally silenced. Silent rDNA repeats may act as ‘back-up’ copies for ribosome biogenesis and have nuclear organization roles. Through Cas9-mediated genome editing in the Arabidopsis thaliana female gametophyte we reduced 45S rDNA copy number to a plateau of ∼10%. Two independent lines had rDNA copy numbers reduced by up to 90% at the T7 generation, named Low Copy Number (LCN) lines. Despite drastic reduction of rDNA copies, rRNA transcriptional rates and steady-state levels remained the same as wild type plants. Gene dosage compensation of rRNA transcript levels was associated with reduction of silencing histone marks at rDNA loci and altered Nucleolar Organiser Region 2 organization. While overall genome integrity of LCN lines appears unaffected, a chromosome segmental duplication occurred in one of the lines. Transcriptome analysis of LCN seedlings identified several shared dysregulated genes and pathways in both independent lines. Cas9 genome editing of rRNA repeats to generate LCN lines provides a powerful technique to elucidate rDNA dosage compensation mechanisms and impacts of low rDNA copy number on genome stability, development, and cellular processes.

scholarly journals The retrotransposon R2 maintains Drosophila ribosomal DNA repeats

2021 ◽  
Author(s):  
Jonathan O Nelson ◽  
Alyssa Slicko ◽  
Yukiko M Yamashita
Keyword(s):  
Ribosomal Dna ◽  
Copy Number ◽  
Double Strand Breaks ◽  
Copy Number Loss ◽  
Dna Repeats ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Male Germline ◽  
Rdna Loci ◽  
Rdna Copy

Ribosomal RNAs (rRNAs) account for 80-90% of all transcripts in eukaryotic cells. To meet this demand, the ribosomal DNA (rDNA) gene that codes for rRNA is tandemly repeated hundreds of times, comprising rDNA loci on eukaryotic chromosomes. This repetitiveness imposes a challenge to maintaining sufficient copy number due to spontaneous intra-chromatid recombination between repetitive units causing copy number loss. The progressive shrinking of rDNA loci from generation to generation could lead to extinction of the lineage, yet the mechanism(s) to counteract spontaneous copy number loss remained unclear. Here, we show that the rDNA-specific retrotransposon R2 is essential for rDNA copy number (CN) maintenance in the Drosophila male germline, despite the perceived disruptive nature of transposable elements. Depletion of R2 led to defective rDNA CN maintenance in multiple contexts, causing a decline in fecundity over generations and eventual extinction of the lineage. Our data suggests that DNA double strand breaks generated by R2 is the initiating event of rDNA CN expansion, stimulating the repair processes proposed to underlie rDNA CN expansion. This study reveals that retrotransposons can provide a benefit to their hosts, contrary to their reputation as genomic parasitic, which may contribute to their widespread success throughout taxa.

scholarly journals Author response: Transgenerational dynamics of rDNA copy number in Drosophila male germline stem cells

2017 ◽  
Author(s):  
Kevin L Lu ◽  
Jonathan O Nelson ◽  
George J Watase ◽  
Natalie Warsinger-Pepe ◽  
Yukiko M Yamashita
Keyword(s):  
Stem Cells ◽  
Copy Number ◽  
Author Response ◽  
Germline Stem Cells ◽  
Male Germline ◽  
Male Germline Stem Cells ◽  
Rdna Copy ◽  
Rdna Copy Number

The correlation between rDNA copy number and genome size in eukaryotes

Genome ◽  
2003 ◽  
Vol 46 (1) ◽  
pp. 48-50 ◽  
Author(s):  
Cheryl D Prokopowich ◽  
T Ryan Gregory ◽  
Teresa J Crease
Keyword(s):  
Genome Size ◽  
Copy Number ◽  
Positive Relationship ◽  
Convincing Evidence ◽  
Rrna Genes ◽  
Strong Positive Relationship ◽  
C Value ◽  
Two Parameters ◽  
Rdna Copy ◽  
Rdna Copy Number

Both rDNA gene multiplicity and genome size vary widely among eukaryotes. For some time, there has been debate regarding any possible relationship between these two parameters. The present study uses data on genome size and rDNA copy number for 162 species of plants and animals to test the association between genome size and rDNA copy number, and provides the first convincing evidence of a strong positive relationship between the two within and among these two groups of organisms. No simple explanations exist for this relationship, but it is nevertheless of clear relevance from both practical and theoretical perspectives.Key words: rRNA genes, C value, genome size.

scholarly journals Transcription of ribosomal genes can cause nondisjunction

2006 ◽  
Vol 173 (6) ◽  
pp. 893-903 ◽  
Author(s):  
Felix Machín ◽  
Jordi Torres-Rosell ◽  
Giacomo De Piccoli ◽  
Jesús A. Carballo ◽  
Rita S. Cha ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Copy Number ◽  
Ribosomal Genes ◽  
Rrna Genes ◽  
Normal Length ◽  
Very High ◽  
Rdna Copy ◽  
Rdna Copy Number ◽  
Genetic Rearrangements ◽  
Chromosome Nondisjunction

Mitotic disjunction of the repetitive ribosomal DNA (rDNA) involves specialized segregation mechanisms dependent on the conserved phosphatase Cdc14. The reason behind this requirement is unknown. We show that rDNA segregation requires Cdc14 partly because of its physical length but most importantly because a fraction of ribosomal RNA (rRNA) genes are transcribed at very high rates. We show that cells cannot segregate rDNA without Cdc14 unless they undergo genetic rearrangements that reduce rDNA copy number. We then demonstrate that cells with normal length rDNA arrays can segregate rDNA in the absence of Cdc14 as long as rRNA genes are not transcribed. In addition, our study uncovers an unexpected role for the replication barrier protein Fob1 in rDNA segregation that is independent of Cdc14. These findings demonstrate that highly transcribed loci can cause chromosome nondisjunction.

scholarly journals Age-dependent ribosomal DNA variations and their effect on cellular function in mammalian cells

2020 ◽  
Author(s):  
Eriko Watada ◽  
Sihan Li ◽  
Yutaro Hori ◽  
Katsunori Fujiki ◽  
Katsuhiko Shirahige ◽  
...  
Keyword(s):  
Ribosomal Rna ◽  
Copy Number ◽  
Mammalian Cells ◽  
Bone Marrow Cells ◽  
Budding Yeast ◽  
Rdna Repeat ◽  
Age Dependent ◽  
Old Mice ◽  
Rdna Copy ◽  
Rdna Copy Number

AbstractThe ribosomal RNA gene, which consists of tandem repetitive arrays (rDNA repeat), is one of the most unstable regions in the genome. The rDNA repeat in the budding yeast is known to become unstable as the cell ages. However, it is unclear how the rDNA repeat changes in ageing mammalian cells. Using quantitative analyses, we identified age-dependent alterations in rDNA copy number and levels of methylation in mice. The degree of methylation and copy number of rDNA from bone marrow cells of 2-year-old mice were increased by comparison to 4-week-old mice in two mouse strains, BALB/cA and C57BL/6. Moreover, the level of pre-rRNA transcripts was reduced in older BALB/cA mice. We also identified many sequence variations among the repeats with two mutations being unique to old mice. These sequences were conserved in budding yeast and equivalent mutations shortened the yeast chronological lifespan. Our findings suggest that rDNA is also fragile in mammalian cells and alterations within this region have a profound effect on cellular function.Author SummaryThe ribosomal RNA gene (rDNA) is one of the most unstable regions in the genome due to its tandem repetitive structure. rDNA copy number in the budding yeast increases and becomes unstable as the cell ages. It is speculated that the rDNA produces an “aging signal” inducing senescence and death. However, it is unclear how the rDNA repeat changes during the aging process in mammalian cells. In this study, we attempted to identify the age-dependent alteration of rDNA in mice. Using quantitative single cell analysis, we show that rDNA copy number increases in old mice bone marrow cells. By contrast, the level of ribosomal RNA production was reduced because of increased levels of DNA methylation that represses transcription. We also identified many sequence variations in the rDNA. Among them, three mutations were unique to old mice and two of them were found in the conserved region in budding yeast. We then established a yeast strain with the old mouse-specific mutations and found this shortened the lifespan of the cells. These findings suggest that rDNA is also fragile in mammalian cells and alteration to this region of the genome affects cellular senescence.

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