A substantial proportion of the genome of many species is derived from transposable elements (TEs). Moreover, through various self-copying mechanisms, TEs continue to proliferate in the genomes of most species. TEs have contributed numerous regulatory, transcript and protein innovations and have also been linked to disease. However, notwithstanding their demonstrated impact, many genomic studies still exclude them because their repetitive nature results in various analytical complexities. Fortunately, a growing array of methods and software tools are being developed to cater for them. This Review presents a summary of computational resources for TEs and highlights some of the challenges and remaining gaps to perform comprehensive genomic analyses that do not simply ‘mask’ repeats.
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This work was supported by a grant from the Canadian Institute for Health Research (CIHR-MOP-115090). P.G.-P. is supported by the Programme de bourses de formation de doctorat du Fonds de Recherche Québec Santé (FRSQ-31874). G.B. is supported by the Fonds de Recherche Québec Santé (FRQS-25348). The authors also thank J.M.M. Monlong and the reviewers for very useful comments on the manuscript.
Nature Reviews Genetics thanks E. Lerat, A. Smit and the other, anonymous reviewer(s) for their contribution to the peer review of this work.
The authors declare no competing interests.
- TE annotation
Assembled genomes are annotated to indicate which sequences are derived from transposable elements (TEs). The annotation reveals which families of TEs are present as well as the percentage of TE-derived sequences in a genome.
- Repression mechanisms
Active transposable elements contain promoters that can initiate transcription. They are ‘silenced’ through various repression mechanisms to prevent transcription and further mobilization.
- Polymorphic insertions
Individual transposable element instances that have not been fixed in a species genome and are present in some re-sequenced genomes but absent from others, such as the reference genome. Polymorphic insertions can be either germline or somatic.
- Long interspersed nuclear element 1
(LINE-1; also known as L1). Autonomous class I transposons that encode reverse transcriptase, endonuclease and RNA-binding proteins that effectively mobilize RNA sequences and create novel insertions.
Primate-specific non-autonomous short interspersed nuclear element retrotransposon. Alus are highly abundant in primate genomes and can mobilize through the long interspersed nuclear element (LINE) retrotransposition machinery.
Primate-specific non-autonomous retrotransposons composed of fragments of Alus and retroviral long terminal repeat elements. The SVA name comes from the fact that they are derived from short interspersed nuclear elements, variable number tandem repeats (VNTRs) and Alu elements. They mobilize through long interspersed nuclear element (LINE) mobilization proteins.
- Germline insertions
Transposable element insertions occurring in the parental germ line or during embryogenesis and shared between all cells of an individual.
- Somatic insertions
Transposable element insertions occurring later in life in a specific tissue. These insertions are unique to one or a subset of cells of an individual.
(Also known as co-opted). A transposable element (TE) for which at least part of its sequence has been recruited to perform a specific function for the host, such as providing a TE-encoded protein with physiological functions. The co-opted sequence has been domesticated.
A transposable element modulating the expression of nearby genes by having part of its sequence acting as a regulatory element.
A transposable element modulating cellular processes distant from its genomic location. Trans-regulation is done via its transcript or encoded protein.
DNA transposons initially identified in fungi that are characterized by the use of tyrosine recombinase instead of transposase for transposition.
Recently identified eukaryotic large DNA transposons (also known as Polintons) encoding up to ten proteins, including some that are similar to virus capsid.
- Multi-mapped reads
Sequencing reads that map ambiguously to more than one location on the reference genome. These are common for repetitive regions including transposable elements.
- Long-read sequencing
Can be achieved by directly sequencing long DNA molecules, such as by using Pacific Biosciences or Oxford Nanopore Technologies platforms. Alternatively, linked-read sequencing of 10X Genomics generates synthetic long reads by barcoding long molecules of DNA and sequencing interspersed short fragments each retaining the originating long molecule barcode, effectively linking these short reads into longer contigs.
- Consensus sequence
Nucleotide sequence representing an approximation of the active transposable element (TE) that gave rise to a group of interspersed repeats. They are generated from a multiple alignment of instances from the same TE family that have accumulated mutations over time.
- Miniature inverted repeat TE
(MITE). A recently coined name for non-autonomous short terminal inverted repeat DNA transposons.
- Short interspersed nuclear elements
(SINEs). Non-autonomous elements for which their propagation is dependent on the retrotransposition machinery of long interspersed nuclear elements (LINEs) in the same genome. They contain an internal RNA polymerase III promoter derived from a small RNA gene, usually a tRNA.
- Nested repeats
Transposable elements (TEs) that inserted in or near previous TE insertions. These are very challenging to detect with short reads.
- Terminal inverted repeats
(TIRs). Repeated sequences that are present in the terminal regions of various transposable elements (TEs) are specific for particular TE families. These motifs contain transposase and DNA binding sites that are essential for transposition of the TE.
Dictyostelium intermediate repeat sequence (DIRS) are classified as a superfamily of long terminal repeat transposons in the RepBase database and as a distinct order and superfamily in the 2007 Wicker unified transposable element classification system.
- Target site duplications
(TSDs). Occur at insertion sites of most transposable elements (TEs), where the host genomic sequence is duplicated surrounding the new TE instance. As the two DNA strands are not cleaved at the exact same location, a few bases in between the two cuts will become duplicated during the second strand synthesis closing the insertion site.
Host genomic DNA that is transcribed and inserted elsewhere in the genome through transposable element (TE) retrotransposition events. These duplicated sequences can be found with or without adjacent TE sequences as TE reverse transcription is often prematurely stopped.
A PCR-free, single-molecule real-time (SMRT) sequencing platform from Pacific Biosciences that produces long reads. Reads are 1–60 kb in length, with a median of 10 kb.
Chromatin immunoprecipitation followed by sequencing (ChIP-seq) consists of the capture and sequencing of DNA that is bound by a protein of interest, such as a transcription factor or modified histone.
Rapid amplification of cDNA ends (RACE) is a method to amplify complete RNA molecules. RACE-seq involves sequencing the RNA molecules amplified through the RACE protocol. It is often used to detect novel transcripts.
Cap analysis of gene expression (CAGE) sequencing is a method to identify transcription start sites through sequencing of 5′ RNA transcripts.
- PIWI-interacting RNA
(piRNA). piRNAs are short non-coding RNA molecules that bind to PIWI proteins. They are established as part of transposable element silencing mechanisms in animals.
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Goerner-Potvin, P., Bourque, G. Computational tools to unmask transposable elements. Nat Rev Genet 19, 688–704 (2018). https://doi.org/10.1038/s41576-018-0050-x
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