DNA Elimination in Ciliates: Transposon Domestication and Genome Surveillance

Chalker, Douglas L.; Yao, Meng-Chao

doi:10.1146/annurev-genet-110410-132432

Cited by 128 publications

(136 citation statements)

References 100 publications

Supporting

Mentioning

133

Contrasting

Unclassified

Order By: Relevance

“…It remains possible that under conditions of physiological stress, a role for this common yet poorly understood polyploid genome alteration may be uncovered. Nevertheless, coupled with studies of programmed DNA elimination in the polyploid macronucleus of ciliates (Chalker and Yao, 2011), under-replication and amplification all represent examples of 'genome flexibility' exhibited by polyploid cells. Further study of such flexibility may lead to novel functions of endoreplication in development.…”

Section: Consequences Of Defective Endoreplication During Developmentmentioning

confidence: 99%

Endoreplication and polyploidy: insights into development and disease

2013

View full text Add to dashboard Cite

SummaryPolyploid cells have genomes that contain multiples of the typical diploid chromosome number and are found in many different organisms. Studies in a variety of animal and plant developmental systems have revealed evolutionarily conserved mechanisms that control the generation of polyploidy and have recently begun to provide clues to its physiological function. These studies demonstrate that cellular polyploidy plays important roles during normal development and also contributes to human disease, particularly cancer.Key words: Cancer, Endocycle, Endomitosis, Endoreplication, Genome instability IntroductionPolyploid cells, which contain multiples of the diploid genome equivalent, have been studied for many years, nearly as long as chromosomes themselves have been studied. Now, over a century after the discovery of polyploidy, we know much about the molecular mechanisms that generate cellular polyploidy, but comparably little regarding the physiological function of the polyploid state. This discrepancy exists despite the frequent occurrence of polyploid cells in most multicellular organisms, as well as in human cancers. An important aspect of deciphering the roles for polyploidy lies in understanding the regulation of endoreplication, a cell cycle variation that generates a polyploid genome by repeated rounds of DNA replication in the absence of cell division. Recent advances show that, although some differences exist in the diverse endoreplication programs found from protists to humans, core principles can be applied. New work in genetic model organisms has identified cases in which programmed endoreplication plays key roles in development. Furthermore, recent evidence indicates that endoreplication can confer genome instability, a major cancer-enabling property. In this Primer (see Box), we review such recent discoveries, focusing on work carried out in the past 3 years, and refer the reader to other comprehensive reviews on this topic Lee et al., 2009). From these new insights emerge unifying themes regarding endoreplication that hold promise of elucidating the advantages, as well as the potential disadvantages, of polyploidy. Endoreplication and developmentEndoreplication is typically studied in the context of endopolyploidy, which refers to the presence of polyploid cells in an otherwise diploid organism. Diverse levels of polyploidy occur throughout nature (Table 1). Although polyploidy is well appreciated in plants , many different animal tissues, including the skin, gut, placenta, liver, brain and blood have polyploid cells (Table 1) (Laird et al., 1980;Corash et al., 1989;Fox et al., 2010; Hedgecock and White, 1985;Melaragno et al., 1993;Sherman, 1972;Unhavaithaya and Orr-Weaver, 2012;Zanet et al., 2010). Interestingly, endoreplication is not limited to multi-cellular organisms, with examples described in ciliated protozoa (Yin et al., 2010) and even bacteria (Mendell et al., 2008).Two primary forms of endoreplication have been described: endocycling and endomitosis (Fig. 1). Endocycles are compos...

show abstract

Section: Consequences Of Defective Endoreplication During Developmentmentioning

confidence: 99%

Endoreplication and polyploidy: insights into development and disease

2013

View full text Add to dashboard Cite

show abstract

“…One intriguing aspect is in the government of genome integrity. For example, noncoding RNA plays key roles in the silencing of transposons in many organisms (van Wolfswinkel and Ketting, 2010) and the elimination of foreign DNAs in bacteria (Bhaya et al, 2011) and ciliated protozoa (Chalker and Yao, 2011;Chalker et al, 2013;Yao et al, 2014). This property affects genome structures both within an organism and through evolution.…”

Section: Introductionmentioning

confidence: 99%

“…These small RNAs are bound by the piwi-related Tetrahymena argonaute proteins Twi1p and Twi11p (Mochizuki et al, 2002;Couvillion et al, 2009;Noto et al, 2015) and are thought to guide heterochromatin targeting through homology recognition, though the targeting mechanism is still unknown. The targeted regions are modified with silencing marks, including specific histone modifications and chromodomain proteins (Taverna et al, 2002;Liu et al, 2004Liu et al, , 2007Yao and Chao, 2005), leading to their excision using a domesticated piggyBac transposase, Tpb2p (Cheng et al, 2010;Chalker and Yao, 2011). Remarkably, injections of dsRNAs into developing cells causes efficient deletion of the corresponding macronuclear DNA from the progeny (Yao et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Dynamic distributions of long double-stranded RNA in Tetrahymena during nuclear development and genome rearrangements

Woo

Chao

Yao

2016

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

Bi-directional non-coding transcripts and their ∼29-nt small RNA products are known to guide DNA deletion in Tetrahymena, leading to the removal of one-third of the genome from developing somatic nuclei. Using an antibody specific for long double-stranded RNAs (dsRNAs), we determined the dynamic subcellular distributions of these RNAs. Conjugation-specific dsRNAs were found and show sequential appearances in parental germline, parental somatic nuclei and finally in new somatic nuclei of progeny. The dsRNAs in germline nuclei and new somatic nuclei are likely transcribed from the sequences destined for deletion; however, the dsRNAs in parental somatic nuclei are unexpected, and PCR analyses suggested that they were transcribed in this nucleus. Deficiency in the RNA interference (RNAi) pathway led to abnormal aggregations of dsRNA in both the parental and new somatic nuclei, whereas accumulation of dsRNAs in the germline nuclei was only seen in the Dicer-like gene mutant. In addition, RNAi mutants displayed an early loss of dsRNAs from developing somatic nuclei. Thus, long dsRNAs are made in multiple nuclear compartments and some are linked to small RNA production whereas others might participate in their regulations.

show abstract

“…Some of these strategies, such as transcriptional silencing by chromatin modifications (e.g., histone methylation, DNA methylation) and posttranscriptional silencing using components of the RNAi machinery, are widespread across eukaryotes (5). In contrast, processes such as DNA elimination in the macronuclei of ciliates show a restricted phyletic distribution (6). Transposons have, in turn, evolved a variety of adaptations that help them survive in host genomes (7).…”

mentioning

confidence: 99%

Lineage-specific expansions of TET/JBP genes and a new class of DNA transposons shape fungal genomic and epigenetic landscapes

Iyer

Zhang

Souza

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

TET/JBP dioxygenases oxidize methylpyrimidines in nucleic acids and are implicated in generation of epigenetic marks and potential intermediates for DNA demethylation. We show that TET/JBP genes are lineage-specifically expanded in all major clades of basidiomycete fungi, with the majority of copies predicted to encode catalytically active proteins. This pattern differs starkly from the situation in most other organisms that possess just a single or a few copies of the TET/JBP family. In most basidiomycetes, TET/ JBP genes are frequently linked to a unique class of transposons, KDZ (Kyakuja, Dileera, and Zisupton) and appear to have dispersed across chromosomes along with them. Several of these elements typically encode additional proteins, including a divergent version of the HMG domain. Analysis of their transposases shows that they contain a previously uncharacterized version of the RNase H fold with multiple distinctive Zn-chelating motifs and a unique insert, which are predicted to play roles in structural stabilization and target sequence recognition, respectively. We reconstruct the complex evolutionary history of TET/JBPs and associated transposons as involving multiple rounds of expansion with concomitant lineage sorting and loss, along with several capture events of TET/ JBP genes by different transposon clades. On a few occasions, these TET/JBP genes were also laterally transferred to certain Ascomycota, Glomeromycota, Viridiplantae, and Amoebozoa. One such is an inactive version, calnexin-independence factor 1 (Cif1), from Schizosaccharomyces pombe, which has been implicated in inducing an epigenetically transmitted prion state. We argue that this unique transposon-TET/JBP association is likely to play important roles in speciation during evolution and epigenetic regulation. methylcytosine | fungal evolution | DNA modification | genomic association I ntragenomic conflicts with diverse mobile elements have played a critical role in shaping cellular genomes (1). In eukaryotes, genomic rearrangements mediated by transposons in germ-line cells promote reproductive isolation of organisms and, accordingly, are implicated in speciation events (2, 3). The mobility of transposons has the potential to disrupt genes by insertion as well as to create new genes or to resurrect inactive ones. Indeed, genomic analyses have revealed that transposons are an important source for both regulatory elements and new DNA-binding domains in transcription factors and chromatin proteins across the tree of life (1, 4). Organisms show a diverse array of strategies to counter mobile elements, supporting the idea of a constant arms race between them and genomes. Some of these strategies, such as transcriptional silencing by chromatin modifications (e.g., histone methylation, DNA methylation) and posttranscriptional silencing using components of the RNAi machinery, are widespread across eukaryotes (5). In contrast, processes such as DNA elimination in the macronuclei of ciliates show a restricted phyletic distribution (6). Transpos...

show abstract

DNA Elimination in Ciliates: Transposon Domestication and Genome Surveillance

Cited by 128 publications

References 100 publications

Endoreplication and polyploidy: insights into development and disease

Endoreplication and polyploidy: insights into development and disease

Dynamic distributions of long double-stranded RNA in Tetrahymena during nuclear development and genome rearrangements

Lineage-specific expansions of TET/JBP genes and a new class of DNA transposons shape fungal genomic and epigenetic landscapes

Contact Info

Product

Resources

About