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Ten Things You Should Know About Transposable Elements

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Ten Things You Should Know About Transposable Elements Ten things you should know about transposable elements The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. Citation Bourque, Guillaume et al. "Ten things you should know about transposable elements." Genome Biology 19 (November 2018): 199 © 2018 The Author(s) As Published https://doi.org/10.1186/s13059-018-1577-z Publisher BioMed Central Version Final published version Citable link http://hdl.handle.net/1721.1/119454 Terms of Use Creative Commons Attribution Detailed Terms http://creativecommons.org/licenses/by/4.0/ Bourque et al. Genome Biology (2018) 19:199 https://doi.org/10.1186/s13059-018-1577-z REVIEW Open Access Ten things you should know about transposable elements Guillaume Bourque1,2* , Kathleen H. Burns3, Mary Gehring4, Vera Gorbunova5, Andrei Seluanov5, Molly Hammell6, Michaël Imbeault7, Zsuzsanna Izsvák8, Henry L. Levin9, Todd S. Macfarlan9, Dixie L. Mager10 and Cédric Feschotte11* by an integrase much like retroviruses [2]. For non-LTR Abstract retrotransposons, which include both long and short in- Transposable elements (TEs) are major components terspersed nuclear elements (LINEs and SINEs), chromo- of eukaryotic genomes. However, the extent of their somal integration is coupled to the reverse transcription impact on genome evolution, function, and disease through a process referred to as target-primed reverse remain a matter of intense interrogation. The rise of transcription [3]. Class 2 elements, also known as DNA genomics and large-scale functional assays has shed transposons, are mobilized via a DNA intermediate, either new light on the multi-faceted activities of TEs and directly through a ‘cut-and-paste’ mechanism [4, 5]or,in implies that they should no longer be marginalized. the case of Helitrons,a‘peel-and-paste’ replicative mech- Here, we introduce the fundamental properties of TEs anism involving a circular DNA intermediate [6]. For de- and their complex interactions with their cellular tailed reviews on individual TE types and transposition environment, which are crucial to understanding mechanisms, we refer the reader to the monograph edited their impact and manifold consequences for organismal by Craig et al. [7]. biology. While we draw examples primarily from Each TE subclass is further divided into subgroups (or mammalian systems, the core concepts outlined superfamilies) that are typically found across a wide here are relevant to a broad range of organisms. range of organisms, but share a common genetic organization and a monophyletic origin. For example, Ty3/gypsy and Ty1/copia elements are two major super- Transposable elements come in many different families of LTR retrotransposons that occur in virtually forms and shapes all major groups of eukaryotes [8]. Similarly, Tc1/mari- Transposable elements (TEs) are DNA sequences that ner, hAT (hobo-Ac-Tam3), and MULEs (Mutator-like el- have the ability to change their position within a genome. ements) are three superfamilies of DNA transposons As a result of their deep evolutionary origins and continu- that are widespread across the eukaryotic tree [9]. At the ous diversification, TEs come in a bewildering variety of most detailed level of TE classification, elements are forms and shapes (Fig. 1). TEs can be divided into two grouped into families or subfamilies, which can be de- major classes based on their mechanism of transposition, fined as a closely related group of elements that can be and each class can be subdivided into subclasses based on traced as descendants of a single ancestral unit [10]. This the mechanism of chromosomal integration. Class 1 ele- ancestral copy can be inferred as a consensus sequence, ments, also known as retrotransposons, mobilize through which is representative of the entire (sub)family [11, 12]. ‘ ’ a copy-and-paste mechanism whereby a RNA intermedi- Thus, in principle, every TE sequence in a genome can ate is reverse-transcribed into a cDNA copy that is inte- be affiliated to a (sub)family, superfamily, subclass, and grated elsewhere in the genome [1]. For long terminal class (Fig. 1). However, much like the taxonomy of spe- repeat (LTR) retrotransposons, integration occurs by cies, the classification of TEs is in constant flux, per- means of a cleavage and strand-transfer reaction catalyzed petually subject to revision due to the discovery of completely novel TE types, the introduction of new * Correspondence: [email protected]; [email protected] levels of granularity in the classification, and ongoing de- 1Department of Human Genetics, McGill University, Montréal, Québec H3A 0G1, Canada velopment of methods and criteria to detect and classify 11Department of Molecular Biology and Genetics, Cornell University, Ithaca, TEs [13, 14]. NY 14850, USA Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Bourque et al. Genome Biology (2018) 19:199 Page 2 of 12 Transposition intermediate RT RNA DNA Class CLASS 1 CLASS 2 Retrotransposons DNA transposons Integration intermediate and mechanism TPRT circDNA?dsDNA circDNA dsDNA circDNA? dsDNA? EN YR IN HUH TP YR IN Subclass Maverick/ Non-LTR DIRS LTR Helitron Cut and paste Crypton Polinton Phylogeny LINE SINE PLE Ty1/copia Ty3/gypsy ERV hAT Tc1/mariner Superfamily Phylogeny LINE-1 Alu Penelope Ty1 Ty3 HERV-H Ac/Ds Tc1 Family R2 B2 Athena copia gypsy HERV-K hobo mos1 Fig. 1 Classification of eukaryotic transposable elements. Schematic and examples showing the key features and relationships between TE classes, subclasses, superfamilies, and families. Blue circles represent TE-encoded enzymes. circDNA circular DNA intermediate, DIRS Dictyostelium repetitive sequence, dsDNA linear double-stranded DNA intermediate, EN endonuclease, IN integrase, PLEs Penelope-like elements, HUH, Rep/Helicase protein with HUH endonuclease activity, RT reverse transcriptase, TP transposase, TPRT target primed reverse transcription, YR tyrosine recombinase (for other abbreviations, see text) TEs are not randomly distributed in the genome rapidly removed from the population. Insertions that The genome may be viewed as an ecosystem inhabited have little or no effects on genome function and host by diverse communities of TEs, which seek to propagate fitness may reach fixation according to the efficiency of and multiply through sophisticated interactions with selection and drift at purging these insertions from the each other and with other components of the cell [15]. population, which vary greatly among species [21]. Se- These interactions encompass processes familiar to ecol- lective forces can explain why some elements are more ogists, such as parasitism, cooperation, and competition likely to be retained in certain genomic locations than [16]. Thus, it is perhaps not surprising that TEs are others [22, 23]. For instance, de novo insertions of the rarely, if ever, randomly distributed in the genome. TEs human LINE 1 (L1) retrotransposon readily occur exhibit various levels of preference for insertion within within (and disrupt) gene exons [24], but very few if certain features or compartments of the genome (Fig. 2). any L1 elements have been fixed within the coding re- These are often guided by opposite selective forces, a gion of human genes [25]. Similarly, no LTR retrotrans- balancing act of facilitating future propagation while poson is known to exhibit insertion preference with mitigating deleterious effects on host cell function. At regard to which DNA strand is transcribed, and yet the most extreme end of the site-selection spectrum, these elements are strongly depleted in the sense orien- many elements have evolved mechanisms to target spe- tation within human introns—most likely due to their cific loci where their insertions are less detrimental to propensity to interfere with gene splicing and polyade- the host but favorable for their propagation [17]. For in- nylation when inserted in sense orientation [11, 26]. stance, several retrotransposons in species as diverse as Perhaps because of some of these shared properties, the slime mold and budding and fission yeast have evolved evolutionary trajectories of TE accumulation in mam- independently, but convergently, the capacity to target mals were found to be conserved across species in spite the upstream regions of genes transcribed by RNA poly- of clade specific differences in TE content. [27]. Thus, merase III, where they do not appear to affect host gene the success and diversity of TEs in a genome are shaped expression but retain the ability to be transcribed them- both by properties intrinsic to the elements as well as selves [17–20]. evolutionary forces acting at the level of the host spe- Natural selection and genetic drift are also powerful cies. A solid comprehension of how these forces act to- forces shaping the distribution and accumulation of gether is paramount to understanding the impact of TEs [21]. Insertions that are strongly deleterious are TEs on organismal biology. Bourque et al. Genome Biology (2018) 19:199 Page 3 of 12 Requires specialized tools Different forms and shapes 10 1 Modifies regulatory Not randomly 2 networks 9 distributed or Creates genes TEs Source of 8 3 and RNAs TEs mutations Genome Immune response or Genome Not just transposition 7 4 rearrangements 6 5 Affects germline and soma Expression vs repression Fig. 2 Ten things you should know about transposable elements (TEs). Examples of how TEs can impact genomes in direct and indirect ways. Blue boxes represent TEs, gray boxes represent canonical exons, and the black box represents a sequencing read.
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