Whats, hows and whys of programmed DNA elimination in<i>Tetrahymena</i>

Noto, Tomoko; Mochizuki, Kazufumi

doi:10.1098/rsob.170172

Cited by 52 publications

(50 citation statements)

References 87 publications

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“…However, we have not identified any transposases or their signatures in Ascaris that might generate the DNA breaks. In ciliates, programmed DNA rearrangements involves the elimination of short internal sequences followed by re-ligation of the boundaries (IES) and many chromosomal break sites (CBS) that lead to new chromosomes and loss of sequences [17][18][19][20][21]. While there is some understanding of the breaks at IESs, the mechanism for the CBS is unknown.…”

Section: Dna Breaksmentioning

confidence: 99%

“…This form of DNA elimination occurs in some parasitic nematodes (ascarids), copepods, ratfish, hagfish, and lampreys [4,[8][9][10][11][12][13][14][15][16]. Programmed DNA rearrangements also occur in ciliates distinguishing the germline from somatic nuclei [17][18][19][20][21]. However, aspects of DNA elimination in metazoa appears mechanistically distinct from that described in ciliates.…”

Section: Introductionmentioning

confidence: 99%

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Comprehensive Chromosome End Remodeling During Programmed DNA Elimination

Wang

Veronezi

Zagoskin

et al. 2020

Preprint

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Germline and somatic genomes are typically the same in a multicellular organism. However, in some organisms including the parasitic nematode Ascaris, programmed DNA elimination leads to a reduced somatic genome compared to germline cells. Previous work on the parasitic nematode Ascaris demonstrated that programmed DNA elimination encompasses high fidelity chromosomal breaks at specific genome locations and loss of specific genome sequences including a major tandem repeat of 120 bp and ~1,000 germline-expressed genes. However, the precise chromosomal locations of the 120 bp repeats, the breaks regions, and the eliminated genes remained unknown. Here, we used PacBio longread sequencing and chromosome conformation capture (Hi-C) to obtain fully assembled chromosomes of Ascaris germline and somatic genomes, enabling a complete chromosomal view of DNA elimination.Surprisingly, we found that all 24 germline chromosomes undergo comprehensive chromosome end remodeling with DNA breaks in their subtelomeric regions and loss of distal sequences including the telomeres at both chromosome ends. All new Ascaris somatic chromosome ends are recapped by de novo telomere healing. We provide an ultrastructural analysis of DNA elimination and show that Ascaris eliminated DNA is incorporated into many double membrane-bound structures, similar to micronuclei, during telophase of a DNA elimination mitosis. These micronuclei undergo dynamic changes including loss of active histone marks and localize to the cytoplasm following daughter nuclei formation and cytokinesis where they form autophagosomes. Comparative analysis of nematode chromosomes suggests that germline chromosome fusions occurred forming Ascaris sex chromosomes that become independent chromosomes following DNA elimination breaks in somatic cells. These studies provide the first chromosomal view and define novel features and functions of metazoan programmed DNA elimination.

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Section: Dna Breaksmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comprehensive Chromosome End Remodeling During Programmed DNA Elimination

Wang

Veronezi

Zagoskin

et al. 2020

Preprint

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“…The eukaryote Tetrahymenia thermophila has an "RNAi-mediated process that directly alters DNA sequence organization" (Mochizuki & Gorovsky 2004). Approximately 12,000 DNA sequences, comprising 46 mega-bases, are deleted (Noto & Mochizuki 2017). DNA fragments removed from Paramecium tetraurelia chromosomes by a dsRNA-guided mechanism are ligated together to form an extrachromosomal element that is transcribed and processed into more dsRNAs (Rechavi & Lev 2017).…”

Section: Deletionmentioning

confidence: 99%

Biosafety considerations of open air genetic engineering. An analysis of the New Zealand Environmental Protection Authority’s reasons for not classifying organisms treated with double-stranded RNA as genetically modified or new organisms

Heinemann

2019

Preprint

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The New Zealand Environmental Protection Authority (EPA) issued a Decision that makes the use of externally applied double-stranded (ds)RNA molecules on eukaryotic cells or organisms technically out of scope of legislation on new organisms, because in its view the treatment does not create new or genetically modified organisms. The Decision rests on the EPA’s conclusion that dsRNA is not heritable and therefore treatments using dsRNA do not modify genes or other genetic material. I found from an independent review of the literature on the topic that each of the major scientific justifications relied upon by the EPA to conclude that exposures to exogenous sources of dsRNA were out of legislative scope was based on either an inaccurate interpretation or failure to consult the research literature on all types of eukaryotes. The Decision also has not taken into account the unique eukaryotic biodiversity of the country. The safe use of RNA-based technology holds promise for addressing complex and persistent challenges in public health, agriculture and conservation. However, the EPA removed regulatory oversight that could prevent the accidental release of viral genes or genomes by failing to restrict the source or means of modifying the dsRNA.

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“…It is conceivable that DNA-splicing-controlled phenotypes in Paramecium have evolved via selection of heritable alternative DNA splicing variants, consistent with previously proposed models of epigenetic evolution (Coyne et al 2012; Allen and Nowacki 2017) . Although cryptic IES excision is thus far the only characterized mechanism of PDE-dependent phenotypic diversification, in principle other sources of somatic variability such as inefficient IES excision could contribute to the emergence of genetic novelties (Catania et al 2013; Catania and Schmitz 2015) and adaptive phenotypic plasticity (Noto and Mochizuki 2017; Noto and Mochizuki 2018) .…”

Section: Introductionmentioning

confidence: 99%

Enhanced plasticity of programmed DNA elimination boosts adaptive potential in suboptimal environments

Vitali

Hagen

Catania

2018

Preprint

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19The impact of ecological changes on the development of new somatic genomes has 20 thus far been neglected. This oversight yields an incomplete understanding of the 21 mechanisms that underlie environmental adaptation and can be tackled leveraging the 22 biological properties of ciliates. When Paramecium reproduces sexually, its polyploid 23 somatic genome regenerates from the germline genome via a developmental process, 24 Programmed DNA elimination (PDE), that involves the removal of thousands of ORF-25 interrupting germline sequences. Here, we demonstrate that exposure to sub-optimal 26 temperatures impacts PDE efficiency, prompting the emergence of hundreds of 27 alternative DNA splicing variants that dually embody cryptic (germline) variation and 28 de novo induced (somatic) mutations. In contrast to trivial biological errors, many of 29 these alternative DNA isoforms display a patterned genomic topography, are 30 epigenetically controlled, inherited trans-somatically, and under purifying selection. 31Developmental thermoplasticity in Paramecium is a likely source of evolutionary 32 innovation. 33 34 Developmental plasticity-the environmentally induced phenotypic variance 35 associated with alternative developmental trajectories-has been proposed to fuel 36 adaptive evolution by initiating phenotypic changes (West-Eberhard 2005; Uller et al. 37 2018). Exploring the molecular mechanisms that underlie developmental plasticity can 38 reveal a direct link between environmental changes and phenotypic differentiation, 39 shedding light on how variation can surface from a single genotype in a stressful 40 environment. This knowledge has important consequences for current understanding 41 of evolutionary processes and human health (Lea et al. 2017b; Lea et al. 2017a). 42 Previous studies in flies, plants, fungi, and vertebrates suggest that 43 environmental changes that alter the molecular chaperone Hsp90's buffering capacity 44 during development can unlock cryptic genetic variation and boost phenotypic 45 diversification (Rutherford and Lindquist 1998; Queitsch et al. 2002; Yeyati et al. 46 2007; Jarosz and Lindquist 2010; Rohner et al. 2013). These observations 47 substantiate an evolutionary model where cryptic developmental variation, which is 48 revealed in response to environmental stress, might become genetically assimilated 49 (Waddington 1953). An alternative mechanism that links genetic and phenotypic 50 variation via environmental stress has also been proposed. Recent studies in flies 51 suggest that environmental stress, rather than exposing cryptic variation, may induce 52 de novo mutations, DNA deletions and transposon insertions (Fanti et al. 2017), 53 which can result from the disruption of a class of germline-specific small RNAs known 54 as Piwi-interacting RNAs (Specchia et al. 2010; Gangaraju et al. 2011). Following 55 stress-induced epigenetic changes, transposon activation or DNA deletions would 56 generate somatic changes, which might ultimately become heritable via de novo 57 germline ...

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Whats, hows and whys of programmed DNA elimination inTetrahymena

Cited by 52 publications

References 87 publications

Comprehensive Chromosome End Remodeling During Programmed DNA Elimination

Comprehensive Chromosome End Remodeling During Programmed DNA Elimination

Biosafety considerations of open air genetic engineering. An analysis of the New Zealand Environmental Protection Authority’s reasons for not classifying organisms treated with double-stranded RNA as genetically modified or new organisms

Enhanced plasticity of programmed DNA elimination boosts adaptive potential in suboptimal environments

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