Prevalence and Dynamics of Ribosomal DNA Micro-heterogeneity Are Linked to Population History in Two Contrasting Yeast Species

James, Stephen A.; West, Claire; Davey, Robert P.; Dicks, Jo; Roberts, Ian N.

doi:10.1038/srep28555

Cited by 4 publications

(2 citation statements)

References 26 publications

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“…The human repeat is ~30% transcribed (ETS, ITS, 18S, 5.8S, 28S) and ~70% non-transcribed (IGS). We found that the regions encoding 18S and 5.8S had virtually no SNVs in either the tumor or normal genomes, suggesting these sequences cannot tolerate mutations, consistent with a previous report in yeasts [ 30 ]. Surprisingly, SNVs were detected in the 28S region, with a similar number in tumor and normal genomes.…”

Section: Resultssupporting

confidence: 91%

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Ribosomal DNA copy number loss and sequence variation in cancer

et al. 2017

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Ribosomal DNA is one of the most variable regions in the human genome with respect to copy number. Despite the importance of rDNA for cellular function, we know virtually nothing about what governs its copy number, stability, and sequence in the mammalian genome due to challenges associated with mapping and analysis. We applied computational and droplet digital PCR approaches to measure rDNA copy number in normal and cancer states in human and mouse genomes. We find that copy number and sequence can change in cancer genomes. Counterintuitively, human cancer genomes show a loss of copies, accompanied by global copy number co-variation. The sequence can also be more variable in the cancer genome. Cancer genomes with lower copies have mutational evidence of mTOR hyperactivity. The PTEN phosphatase is a tumor suppressor that is critical for genome stability and a negative regulator of the mTOR kinase pathway. Surprisingly, but consistent with the human cancer genomes, hematopoietic cancer stem cells from a Pten-/- mouse model for leukemia have lower rDNA copy number than normal tissue, despite increased proliferation, rRNA production, and protein synthesis. Loss of copies occurs early and is associated with hypersensitivity to DNA damage. Therefore, copy loss is a recurrent feature in cancers associated with mTOR activation. Ribosomal DNA copy number may be a simple and useful indicator of whether a cancer will be sensitive to DNA damaging treatments.

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Section: Resultssupporting

confidence: 91%

“…SNVs were binned for each region of the repeat ( Fig 4B ). Previous work in yeast has suggested the most variable region is the non-transcribed portion, because mutations here might have the least functional consequences [ 30 ]. The human repeat is ~30% transcribed (ETS, ITS, 18S, 5.8S, 28S) and ~70% non-transcribed (IGS).…”

Section: Resultsmentioning

confidence: 99%

Ribosomal DNA copy number loss and sequence variation in cancer

et al. 2017

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Evolutionary Dynamics of Copy Number and Meiotic Recombination in Murine 5S rDNA: Possible Involvement of Natural Selection

et al. 2018

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We investigated evolutionary trends of the 5S ribosomal RNA gene in the house mouse, Mus musculus. First, we assessed the 5S cluster and copy numbers in eight laboratory strains by pulsed-field gel electrophoresis. The copy numbers in seven lines were estimated to be around 130-170 copies per cluster, with 63 copies in the remaining strain, implying that the copy number can change drastically and has been maintained under certain evolutionary constraints at ~ 140 copies. Second, we addressed the frequency of meiotic recombination mediated by the 5S cluster by performing a mating experiment with laboratory strains, and found that the 5S cluster did not accelerate recombination events. Third, we surveyed recombination events of the 5S-containing chromosome region in wild mice from the Japanese Islands, where the two subspecies lineages, M. m. castaneus and M. m. musculus, are historically mingled, and found that the influence of the 5S cluster on meiotic recombination was limited. Finally, we examined the nucleotide diversity of six genes in the neighboring regions of the 5S cluster and found reduced genetic diversity in the regions on both sides of the cluster, suggesting the involvement of either positive or background selection in the population-level sequence similarity of the 5S clusters. Therefore, the mouse 5S genes are considered to be evolving toward sequence similarity within a given cluster by certain intrachromosomal mechanisms and toward sharing of a specific 5S cluster within a population by certain selective processes.

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Species clarification of oyster mushrooms in China and their DNA barcoding

Liu

et al. 2017

Mycol Progress

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Prevalence and Dynamics of Ribosomal DNA Micro-heterogeneity Are Linked to Population History in Two Contrasting Yeast Species

Cited by 4 publications

References 26 publications

Ribosomal DNA copy number loss and sequence variation in cancer

Ribosomal DNA copy number loss and sequence variation in cancer

Evolutionary Dynamics of Copy Number and Meiotic Recombination in Murine 5S rDNA: Possible Involvement of Natural Selection

Species clarification of oyster mushrooms in China and their DNA barcoding

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