Human ribosomal RNA gene arrays display a broad range of palindromic structures

Caburet, Sandrine; Conti, Chiara; Schurra, Catherine; Lebofsky, Ronald; Edelstein, Stuart J.; Bensimon, Aaron

doi:10.1101/gr.3970105

Cited by 133 publications

(143 citation statements)

References 45 publications

(58 reference statements)

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“…The low-confidence polymorphisms occur in areas of low-sequence quality, and thus, we believe that most of them are unlikely to be real, but we have included them for completeness. We found no evidence for any rearranged rDNA units, such as those found recently in humans (Caburet et al 2005) in any of the five species.…”

Section: Resultsmentioning

confidence: 52%

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Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

Ganley¹,

Kobayashi²

2007

Genome Res.

328

268

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Repeat families within genomes are often maintained with similar sequences. Traditionally, this has been explained by concerted evolution, where repeats in an array evolve "in concert" with the same sequence via continual turnover of repeats by recombination. Another form of evolution, birth-and-death evolution, can also explain this pattern, although in this case selection is the critical force maintaining the repeats. The level of intragenomic variation is the key difference between these two forms of evolution. The prohibitive size and repetitive nature of large repeat arrays have made determination of the absolute level of intragenomic repeat variability difficult, thus there is little evidence to support concerted evolution over birth-and-death evolution for many large repeat arrays. Here we use whole-genome shotgun sequence data from the genome projects of five fungal species to reveal absolute levels of sequence variation within the ribosomal RNA gene repeats (rDNA). The level of sequence variation is remarkably low. Furthermore, the polymorphisms that are detected are not functionally constrained and seem to exist beneath the level of selection. These results suggest the rDNA is evolving via concerted evolution. Comparisons with a repeat array undergoing birth-and-death evolution provide a clear contrast in the level of repeat array variation between these two forms of evolution, confirming that the rDNA indeed does evolve via concerted evolution. These low levels of intra-genomic variation are consistent with a model of concerted evolution in which homogenization is very rapid and efficiently maintains highly similar repeat arrays.[Supplemental material is available online at www.genome.org.]Repetitive elements are an abundant feature of genomes (Britten and Kohne 1968) and play critical roles in cell biology, genome structure, and adaptive evolution (Andersson et al. 1998;Shapiro and von Sternberg 2005). In many cases, repeats from a repeat family are highly similar to one another within a genome, a pattern that persists through evolutionary time even though sequence differences are apparent between species (Brown et al. 1972). Thus, the repeats seem to be maintained as a coherent family. This pattern is contrary to the expectations of conventional evolution, where repeats are expected to evolve independently ( Fig. 1) and diverge with time. This unusual mode of evolution, where repeats within a genome are more similar to each other than they are to "orthologous" repeats in a related species, is defined as concerted evolution (Zimmer et al. 1980). The molecular process responsible for concerted evolution is known as homogenization (Dover 1982), and although not fully elucidated, is thought to involve continual turnover of repeat copies by unequal recombination (e.g., Smith 1973;Szostak and Wu 1980;Kobayashi et al. 1998). However, recent studies have shown that several repeat families previously thought to evolve by concerted evolution actually evolve via a different evolutionary process known as birth-...

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Section: Resultsmentioning

confidence: 52%

“…comm.). Finally, variation in the structural arrangement of repeat units has been detected within some species (Caburet et al 2005), but we do not yet know how widespread this phenomenon is.…”

Section: Discussionmentioning

confidence: 99%

Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

Ganley¹,

Kobayashi²

2007

Genome Res.

328

268

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“…The associations are expected due to the close physical linkage between the components of the 45S rDNA array. Nevertheless, abnormally rearranged rDNA loci might contribute to variability in dosage between rDNA components [18][19][20] and might account for the weaker association between the 18S and the 35S components (5.8S and 28S). In terms of the range of our computational rDNA dosage measurements, our results are consistent with previous experimental estimates of 45S dosage measured by the cumulative physical size of the rDNA clusters 21,22 .…”

Section: Resultsmentioning

confidence: 99%

Ribosomal DNA copy number is coupled with gene expression variation and mitochondrial abundance in humans

et al. 2014

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Ribosomes are essential intracellular machines composed of proteins and RNA molecules. The DNA sequences (rDNA) encoding ribosomal RNAs (rRNAs) are tandemly repeated and give origin to the nucleolus. Here we develop a computational method for estimating rDNA dosage (copy number) and mitochondrial DNA abundance using whole-genome short-read DNA sequencing. We estimate these attributes across hundreds of human genomes and their association with global gene expression. The analyses uncover abundant variation in rDNA dosage that is coupled with the expression of hundreds of functionally coherent gene sets. These include associations with genes coding for chromatin components that target the nucleolus, including CTCF and HP1b. Finally, the data show an inverse association between rDNA dosage and mitochondrial DNA abundance that is manifested across genotypes. Our findings uncover a novel and cryptic source of hypervariable genomic diversity with global regulatory consequences (ribosomal eQTL) in humans. The variation provides a mechanism for cellular homeostasis and for rapid and reversible adaptation.

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“…IRs might not be accurately represented in the current human genome sequences, since DNA IR sequences are well known to be unstable upon cloning in Escherichia coli. DNA IRs may also exist as a form of genetic polymorphism among individuals (7). Further mapping of the epicenters of large palindromes should determine genomic and genetic attributes that lead to initial palindrome formation in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Intrastrand Annealing Leads to the Formation of a Large DNA Palindrome and Determines the Boundaries of Genomic Amplification in Human Cancer

Tanaka

Cao

Bergstrom

et al. 2007

Molecular and Cellular Biology

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Amplification of large chromosomal regions (gene amplification) is a common somatic alteration in human cancer cells and often is associated with advanced disease. A critical event initiating gene amplification is a DNA double-strand break (DSB), which is immediately followed by the formation of a large DNA palindrome. Large DNA palindromes are frequent and nonrandomly distributed in the genomes of cancer cells and facilitate a further increase in copy number. Although the importance of the formation of large DNA palindromes as a very early event in gene amplification is widely recognized, it is not known how a DSB is resolved to form a large DNA palindrome and whether any local DNA structure determines the location of large DNA palindromes. We show here that intrastrand annealing following a DNA double-strand break leads to the formation of large DNA palindromes and that DNA inverted repeats in the genome determine the efficiency of this event. Furthermore, in human Colo320DM cancer cells, a DNA inverted repeat in the genome marks the border between amplified and nonamplified DNA. Therefore, an early step of gene amplification is a regulated process that is facilitated by DNA inverted repeats in the genome.

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Human ribosomal RNA gene arrays display a broad range of palindromic structures

Cited by 133 publications

References 45 publications

Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

Highly efficient concerted evolution in the ribosomal DNA repeats: Total rDNA repeat variation revealed by whole-genome shotgun sequence data

Ribosomal DNA copy number is coupled with gene expression variation and mitochondrial abundance in humans

Intrastrand Annealing Leads to the Formation of a Large DNA Palindrome and Determines the Boundaries of Genomic Amplification in Human Cancer

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