Which transposable elements are active in the human genome?

Mills, Ryan E.; Bennett, E. Andrew; Iskow, Rebecca C.; Devine, Scott E.

doi:10.1016/j.tig.2007.02.006

Cited by 438 publications

(431 citation statements)

References 92 publications

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“…Seventy (53%) TUs are repeat mosaics, combining exonic repeat classes. Some TUs exhibited complex, higher-order repeats, conceptually analogous to SVA sequences (19). Only 14 TUs were devoid of interspersed repeats.…”

Section: Exons and Promoters Of Many Primate-specific Tus Overlap Inter-mentioning

confidence: 99%

Global discovery of primate-specific genes in the human genome

Tay

Blythe

Lipovich

2009

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

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The genomic basis of primate phenotypic uniqueness remains obscure, despite increasing genome and transcriptome sequence data availability. Although factors such as segmental duplications and positive selection have received much attention as potential drivers of primate phenotypes, single-copy primate-specific genes are poorly characterized. To discover such genes genomewide, we screened a catalog of 38,037 human transcriptional units (TUs), compiled from EST and cDNA sequences in conjunction with the FANTOM3 transcriptome project. We identified 131 TUs from transcribed sequences residing within primate-specific insertions in 9-species sequence alignments and outside of segmental duplications. Exons of 120 (92%) of the TUs contained interspersed repeats, indicating that repeat insertions may have contributed to primate-specific gene genesis. Fifty-nine (46%) primate-specific TUs may encode proteins. Although primate-specific TU transcript lengths were comparable to known human gene mRNA lengths overall, 92 (70%) primate-specific TUs were single-exon. Thirty-two (24%) primate-specific TUs were localized to subtelomeric and pericentromeric regions. Forty (31%) of the TUs were nested in introns of known genes, indicating that primate-specific TUs may arise within older, protein-coding regions. Primate-specific TUs were preferentially expressed in reproductive organs and tissues ( P < 0.011), consistent with the expectation that emergence of new, lineage-specific genes may accompany speciation or reproduction. Of the 33 primate-specific TUs with human Affymetrix microarray probe support, 21 were differentially expressed in human teratozoospermia. In addition to elucidating the likely functional relevance of primate-specific TUs to reproduction, we present a set of primate-specific genes for future functional studies, and we implicate nonduplicated pericentromeric and subtelomeric regions in gene genesis.

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Section: Exons and Promoters Of Many Primate-specific Tus Overlap Inter-mentioning

confidence: 99%

Global discovery of primate-specific genes in the human genome

Tay

Blythe

Lipovich

2009

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

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“…In contrast, the second pattern, first observed in Coprinopsis and Laccaria, is one of massive expansions, often with 10 or more copies frequently coupled with transposons. Strikingly, unlike typical transposon-associated genes, where only a few of the many copies are active in a genome (17), analysis of the TET/JBP domains in the above mushrooms showed that the majority of them are predicted to be catalytically active (12).…”

mentioning

confidence: 83%

“…This high fraction of active transposase domains is reminiscent of the active DNA transposons in the micronucleus of the ciliate Oxytricha trifallax (11). It is notably different from retrotransposons and retroviruslike and DIRS-1-like retrotransposons (22), as well as DNA elements, such as Tigger, where the majority of copies tend to have inactive domains (17). This suggests that the transposases of at least a subset of KDZ elements might have functional consequences for the genomes harboring them, comparable to the O. trifallax elements involved in genome rearrangements during macronuclear maturation (11).…”

Section: Transposase_zisuptonmentioning

confidence: 98%

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.

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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...

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“…Activity of the old AluJ/S subfamilies declined while being replaced by the younger Y subfamily (;100,000 copies) (Shen et al 1991). Subsets of the Y subfamilies are the only known Alu elements currently active in the human genome, with variants of the Y, Ya, and Yb lineages currently dominating activity (Deininger and Batzer 1999;Hedges et al 2004;Mills et al 2007;Belancio et al 2008). There are ;900,000 older subfamily elements in the genome, predominately variants of the Alu S and J (Wang et al 2006), and yet no de novo disease-associated insertions of these older elements have been found (Belancio et al 2008).…”

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confidence: 99%

Diverse cis factors controlling Alu retrotransposition: What causes Alu elements to die?

Comeaux¹,

Roy-Engel²,

Hedges³

et al. 2009

Genome Res.

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The human genome contains nearly 1.1 million Alu elements comprising roughly 11% of its total DNA content. Alu elements use a copy and paste retrotransposition mechanism that can result in de novo disease insertion alleles. There are nearly 900,000 old Alu elements from subfamilies S and J that appear to be almost completely inactive, and about 200,000 from subfamily Y or younger, which include a few thousand copies of the Ya5 subfamily which makes up the majority of current activity. Given the much higher copy number of the older Alu subfamilies, it is not known why all of the active Alu elements belong to the younger subfamilies. We present a systematic analysis evaluating the observed sequence variation in the different sections of an Alu element on retrotransposition. The length of the longest number of uninterrupted adenines in the A-tail, the degree of A-tail heterogeneity, the length of the 3′ unique end after the A-tail and before the RNA polymerase III terminator, and random mutations found in the right monomer all modulate the retrotransposition efficiency. These changes occur over different evolutionary time frames. The combined impact of sequence changes in all of these regions explains why young Alus are currently causing disease through retrotransposition, and the old Alus have lost their ability to retrotranspose. We present a predictive model to evaluate the retrotransposition capability of individual Alu elements and successfully applied it to identify the first putative source element for a disease-causing Alu insertion in a patient with cystic fibrosis.

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Which transposable elements are active in the human genome?

Cited by 438 publications

References 92 publications

Global discovery of primate-specific genes in the human genome

Global discovery of primate-specific genes in the human genome

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

Diverse cis factors controlling Alu retrotransposition: What causes Alu elements to die?

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