Copy number variation of ribosomal DNA and Pokey transposons in natural populations of Daphnia

While nuclear small subunit ribosomal DNA (nSSU rDNA) is the most commonly-used gene marker in studying phylogeny, ecology, abundance, and biodiversity of microbial eukaryotes, mitochondrial small subunit ribosomal DNA (mtSSU rDNA) provides an alternative. Recently, both copy number variation and sequence variation of nSSU rDNA have been demonstrated for diverse organisms, which can contribute to misinterpretation of microbiome data. Given this, we explore patterns for mtSSU rDNA among 13 selected ciliates (representing five classes), a major component of microbial eukaryotes, estimating copy number and sequence variation and comparing to that of nSSU rDNA. Our study reveals: (1) mtSSU rDNA copy number variation is substantially lower than that for nSSU rDNA; (2) mtSSU rDNA copy number ranges from 1.0 × 104 to 8.1 × 105; (3) a most common sequence of mtSSU rDNA is also found in each cell; (4) the sequence variation of mtSSU rDNA are mainly indels in poly A/T regions, and only half of species have sequence variation, which is fewer than that for nSSU rDNA; and (5) the polymorphisms between haplotypes of mtSSU rDNA would not influence the phylogenetic topology. Together, these data provide more insights into mtSSU rDNA as a powerful marker especially for microbial ecology studies.

Download Full-text

Ribosomal DNA and Stellate gene copy number variation on the Y chromosome of Drosophila melanogaster.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.86.6.1944 ◽

1989 ◽

Vol 86 (6) ◽

pp. 1944-1948 ◽

Cited By ~ 51

Author(s):

E. M. Lyckegaard ◽

A. G. Clark

Keyword(s):

Drosophila Melanogaster ◽

Copy Number Variation ◽

Y Chromosome ◽

Ribosomal Dna ◽

Copy Number ◽

Gene Copy Number ◽

Gene Copy ◽

Gene Copy Number Variation ◽

Number Variation

Download Full-text

Concerted copy number variation balances ribosomal DNA dosage in human and mouse genomes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1416878112 ◽

2015 ◽

Vol 112 (8) ◽

pp. 2485-2490 ◽

Cited By ~ 89

Author(s):

John G. Gibbons ◽

Alan T. Branco ◽

Susana A. Godinho ◽

Shoukai Yu ◽

Bernardo Lemos

Keyword(s):

Ribosomal Dna ◽

Copy Number ◽

Sequence Similarity ◽

Natural Populations ◽

45S Rdna ◽

Rdna Array ◽

Number Variation ◽

Dosage Balance ◽

5S And 45S Rdna ◽

Cellular Components

Tandemly repeated ribosomal DNA (rDNA) arrays are among the most evolutionary dynamic loci of eukaryotic genomes. The loci code for essential cellular components, yet exhibit extensive copy number (CN) variation within and between species. CN might be partly determined by the requirement of dosage balance between the 5S and 45S rDNA arrays. The arrays are nonhomologous, physically unlinked in mammals, and encode functionally interdependent RNA components of the ribosome. Here we show that the 5S and 45S rDNA arrays exhibit concerted CN variation (cCNV). Despite 5S and 45S rDNA elements residing on different chromosomes and lacking sequence similarity, cCNV between these loci is strong, evolutionarily conserved in humans and mice, and manifested across individual genotypes in natural populations and pedigrees. Finally, we observe that bisphenol A induces rapid and parallel modulation of 5S and 45S rDNA CN. Our observations reveal a novel mode of genome variation, indicate that natural selection contributed to the evolution and conservation of cCNV, and support the hypothesis that 5S CN is partly determined by the requirement of dosage balance with the 45S rDNA array. We suggest that human disease variation might be traced to disrupted rDNA dosage balance in the genome.

Download Full-text

Divergence patterns of genic copy number variation in natural populations of the house mouse (Mus musculus domesticus) reveal three conserved genes with major population-specific expansions

Genome Research ◽

10.1101/gr.187187.114 ◽

2015 ◽

Vol 25 (8) ◽

pp. 1114-1124 ◽

Cited By ~ 46

Author(s):

Željka Pezer ◽

Bettina Harr ◽

Meike Teschke ◽

Hiba Babiker ◽

Diethard Tautz

Keyword(s):

Copy Number Variation ◽

House Mouse ◽

Mus Musculus ◽

Copy Number ◽

Natural Populations ◽

Mus Musculus Domesticus ◽

Conserved Genes ◽

Number Variation

Download Full-text

Copy numbers of 45S and 5S ribosomal DNA arrays lack meaningful correlation in humans

10.1101/2020.07.06.189753 ◽

2020 ◽

Author(s):

Ashley N. Hall ◽

Tychele N. Turner ◽

Christine Queitsch

Keyword(s):

Copy Number Variation ◽

Ribosomal Dna ◽

Copy Number ◽

1000 Genomes Project ◽

High Coverage ◽

1000 Genomes ◽

Copy Numbers ◽

Number Variation ◽

Rdna Copy ◽

Rdna Copy Number

AbstractThe ribosomal DNA genes are tandemly arrayed in most eukaryotes and exhibit vast copy number variation. There is growing interest in integrating this variation into genotype-phenotype associations. Here, we explored a possible association of rDNA copy number variation with autism spectrum disorder and found no difference between probands and unaffected siblings. However, rDNA copy number estimates from whole genome sequencing are error-prone, so we sought to use pulsed-field gel electrophoresis, a classic gold-standard method, to validate rDNA copy number genotypes. The electrophoresis approach is not readily applicable to the human 45S arrays due to their size and location on five separate chromosomes; however, it should accurately resolve copy numbers for the shorter 5S arrays that reside on a single chromosome. Previous studies reported tightly correlated, concerted copy number variation between the 45S and 5S arrays, which should enable the validation of 45S copy number estimates with CHEF-gel-verified 5S copy numbers. Here, we show that the previously reported strong concerted copy number variation is likely an artifact of variable data quality in the earlier published 1000 Genomes Project sequences. We failed to detect a meaningful correlation between 45S and 5S copy numbers in the large, high-coverage Simons Simplex Collection dataset as well as in the recent high-coverage 1000 Genomes Project sequences. Our findings illustrate the challenge of genotyping repetitive DNA regions accurately and call into question the accuracy of recently published studies of rDNA copy number variation in cancers and aging that relied on diverse publicly available resources for sequence data.

Download Full-text

Gene copy number variation in natural populations of Plasmodium falciparum in Eastern Africa

BMC Genomics ◽

10.1186/s12864-018-4689-7 ◽

2018 ◽

Vol 19 (1) ◽

Cited By ~ 6

Author(s):

Joan Simam ◽

Martin Rono ◽

Joyce Ngoi ◽

Mary Nyonda ◽

Sachel Mok ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Copy Number Variation ◽

Copy Number ◽

Natural Populations ◽

Gene Copy Number ◽

Eastern Africa ◽

Gene Copy ◽

Gene Copy Number Variation ◽

Number Variation

Download Full-text

Genetic context and proliferation determine contrasting patterns of copy number amplification and loss for 5S and 45S ribosomal DNA arrays in cancer

10.1101/154120 ◽

2017 ◽

Cited By ~ 1

Author(s):

Meng Wang ◽

Bernardo Lemos

Keyword(s):

Copy Number Variation ◽

Ribosomal Dna ◽

Copy Number ◽

5S Rdna ◽

45S Rdna ◽

Rdna Array ◽

Number Variation ◽

Proliferating Cell ◽

Rdna Copy ◽

Rdna Copy Number

AbstractThe multicopy 45S ribosomal DNA (45S rDNA) array gives origin to the nucleolus, the first discovered nuclear organelle, site of Poll I 45S rRNA transcription and key regulator of cellular metabolism, DNA repair response, genome stability, and global epigenetic states. The multicopy 5S ribosomal DNA array (5S rDNA) is located on a separate chromosome, encodes the 5S rRNA transcribed by Pol III, and exhibits concerted copy number variation (cCNV) with the 45S rDNA array in human blood. Here we combined genomic data from >700 tumors and normal tissues to provide a portrait of ribosomal DNA variation in human tissues and cancers of diverse mutational signatures. We show that most cancers undergo coupled 5S rDNA array amplification and 45S rDNA loss, with abundant inter-individual variation in rDNA copy number of both arrays, and concerted modulation of 5S-45S copy number in some but not all tissues. Analysis of genetic context revealed associations between the presence of specific somatic alterations, such as P53 mutations in stomach and lung adenocarcinomas, and coupled 5S gain / 45S loss. Finally, we show that increased proliferation rates along cancer lineages can partially explain contrasting copy number changes in the 5S and 45S rDNA arrays. We suggest that 5S rDNA amplification facilitates increased ribosomal synthesis in cancer, whereas 45S rDNA loss emerges as a byproduct of transcription-replication conflict in highly proliferating tumor cells. Our results highlight the tissue- specificity of concerted copy number variation and uncover contrasting changes in 5S and 45S rDNA copy number along rapidly proliferating cell lineages.Lay SummaryThe 45S and 5S ribosomal DNA (rDNA) arrays contain hundreds of rDNA copies, with substantial variability across individuals and species. Although physically unlinked, both arrays exhibit concerted copy number variation. However, whether concerted copy number is universally observed across all tissues is unknown. It also remains unknown if rDNA copy number may vary in tissues and cancer lineages. Here we showed that most cancers undergo coupled 5S rDNA array amplification and 45S rDNA loss, and concerted 5S-45S copy number variation in some but not all tissues. The coupled 5S amplification and 45S loss is associated with the presence of certain somatic genetic variations, as well as increased cancerous cell proliferation rate. Our research highlights the tissue- specificity of concerted copy number variation and uncover contrasting changes in rDNA copy number along rapidly proliferating cell lineages. Our observations raise the prospects of using 5S and 45S ribosomal DNA states as indicators of cancer status and targets in new strategies for cancer therapy.

Download Full-text

Repetitive DNA Profiles Reveal Evidence of Rapid Genome Evolution and Reflect Species Boundaries in Ground Beetles

Systematic Biology ◽

10.1093/sysbio/syaa030 ◽

2020 ◽

Vol 69 (6) ◽

pp. 1137-1148 ◽

Cited By ~ 2

Author(s):

John S Sproul ◽

Lindsey M Barton ◽

David R Maddison

Keyword(s):

Copy Number Variation ◽

Comparative Study ◽

Genome Evolution ◽

Ribosomal Dna ◽

Species Delimitation ◽

Copy Number ◽

Species Boundaries ◽

Genome Architecture ◽

Genomic Architecture ◽

Number Variation

Abstract Genome architecture is a complex, multidimensional property of an organism defined by the content and spatial organization of the genome’s component parts. Comparative study of entire genome architecture in model organisms is shedding light on mechanisms underlying genome regulation, evolution, and diversification, but such studies require costly analytical approaches which make extensive comparative study impractical for most groups. However, lower-cost methods that measure a single architectural component (e.g., distribution of one class of repeats) have potential as a new data source for evolutionary studies insofar as that measure correlates with more complex biological phenomena, and for which it could serve as part of an explanatory framework. We investigated copy number variation (CNV) profiles in ribosomal DNA (rDNA) as a simple measure reflecting the distribution of rDNA subcomponents across the genome. We find that signatures present in rDNA CNV profiles strongly correlate with species boundaries in the breve species group of Bembidion, and vary across broader taxonomic sampling in Bembidion subgenus Plataphus. Profiles of several species show evidence of re-patterning of rDNA-like sequences throughout the genome, revealing evidence of rapid genome evolution (including among sister pairs) not evident from analysis of traditional data sources such as multigene data sets. Major re-patterning of rDNA-like sequences has occurred frequently within the evolutionary history of Plataphus. We confirm that CNV profiles represent an aspect of genomic architecture (i.e., the linear distribution of rDNA components across the genome) via fluorescence in-situ hybridization. In at least one species, novel rDNA-like elements are spread throughout all chromosomes. We discuss the potential of copy number profiles of rDNA, or other repeats, as a low-cost tool for incorporating signal of genomic architecture variation in studies of species delimitation and genome evolution. [Bembidion; Carabidae; copy number variation profiles; rapid genome evolution; ribosomal DNA; species delimitation.]

Download Full-text

A new method for determining ribosomal DNA copy number shows differences between Saccharomyces cerevisiae populations

10.1101/2021.01.21.427686 ◽

2021 ◽

Author(s):

Diksha Sharma ◽

Sylvie Hermann-Le Denmat ◽

Nicholas J. Matzke ◽

Katherine Hannan ◽

Ross D. Hannan ◽

...

Keyword(s):

Saccharomyces Cerevisiae ◽

Copy Number Variation ◽

Ribosomal Dna ◽

Copy Number ◽

Whole Genome Sequence ◽

Whole Genome ◽

Copy Numbers ◽

Number Variation ◽

Rdna Copy ◽

Rdna Copy Number

AbstractRibosomal DNA genes (rDNA) encode the major ribosomal RNAs (rRNA) and in eukaryotic genomes are typically present as one or more arrays of tandem repeats. Species have characteristic rDNA copy numbers, ranging from tens to thousands of copies, with the number thought to be redundant for rRNA production. However, the tandem rDNA repeats are prone to recombination-mediated changes in copy number, resulting in substantial intra-species copy number variation. There is growing evidence that these copy number differences can have phenotypic consequences. However, we lack a comprehensive understanding of what determines rDNA copy number, how it evolves, and what the consequences are, in part because of difficulties in quantifying copy number. Here, we developed a genomic sequence read approach that estimates rDNA copy number from the modal coverage of the rDNA and whole genome to help overcome limitations in quantifying copy number with existing mean coverage-based approaches. We validated our method using strains of the yeast Saccharomyces cerevisiae with previously-determined rDNA copy numbers, and then applied our pipeline to investigate rDNA copy number in a global sample of 788 yeast isolates. We found that wild yeast have a mean copy number of 92, consistent with what is reported for other fungi but much lower than in laboratory strains. We also show that different populations have different rDNA copy numbers. These differences can partially be explained by phylogeny, but other factors such as environment are also likely to contribute to population differences in copy number. Our results demonstrate the utility of the modal coverage method, and highlight the high level of rDNA copy number variation within and between populations.Author summaryThe ribosomal RNA gene repeats (rDNA) form large tandem repeat arrays in most eukaryote genomes. Their tandem arrangement makes the rDNA prone to copy number variation, and there is increasing evidence that this copy number variation has phenotypic consequences. However, difficulties in measuring rDNA copy number hamper investigation into rDNA copy number dynamics and their significance. Here we developed a novel bioinformatics method for measuring rDNA copy number from whole genome sequence data that is based on the modal sequence read coverage. We established parameters for optimal performance of the method and validated it using yeast strains of known rDNA copy numbers. We then applied the method to a dataset of almost 800 global yeast isolates and demonstrate that yeast populations have different rDNA copy numbers that partially correlate with phylogeny. Our work provides a simple and accurate method for determining rDNA copy number that leverages the growing number of whole genome datasets, and highlights the dynamic nature of rDNA copy number.

Download Full-text