Transposable elements: genome innovation, chromosome diversity, and centromere conflict

Chromosome Res https://doi.org/10.1007/s10577-017-9569-5 REVIEW Transposable elements: genome innovation, chromosome diversity, and centromere conflict Savannah J. Klein & Rachel J. O’Neill Received: 10 October 2017 / Revised: 5 December 2017 / Accepted: 12 December 2017 # The Author(s) 2018. This article is an open access publication Abstract Although it was nearly 70 years ago when transposable elements (TEs) were first discovered Bjumping^ from one genomic location to another, TEs are now recognized as contributors to genomic innovations as well as genome instability across a wide variety of species. In this review, we illustrate the ways in which active TEs, specifically retroelements, can create novel chromosome rearrangements and impact gene expression, leading to disease in some cases and speciesspecific diversity in others. We explore the ways in which eukaryotic genomes have evolved defense mechanisms to temper TE activity and the ways in which TEs continue to influence genome structure despite being rendered transpositionally inactive. Finally, we focus on the role of TEs in the establishment, maintenance, and stabilization of critical, yet rapidly evolving, chromosome features: eukaryotic centromeres. Across centromeres, specific types of TEs participate in genomic conflict, a balancing act wherein they are actively inserting into centromeric domains yet are harnessed for the recruitment of centromeric histones and potentially new centromere formation. Keywords Centromeric retroelement . Satellite . Transposable element . TE . Genome defense . Chromosome evolution . Conflict Responsible Editor: Beth A. Sullivan S. J. Klein : R. J. O’Neill (*) Institute for Systems Genomics and Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA e-mail: Abbreviations TE transposable element LTR long terminal repeat LINE long interspersed nuclear element SINE short interspersed nuclear element SVA SINE-VNTR-Alu VNTR variable number tandem repeat HERV human endogenous retrovirus UTR untranslated region ORF open reading frame RNP ribonuclear protein EN endonuclease RT reverse transcriptase TPRT target primed reverse transcription TSD target site duplication piRNA piwi interacting RNA CENP centromere protein H3 histone 3 Ddm1 decrease in DNA methylation 1 dsRNA double-stranded RNA RNAi RNA interference siRNA short interfering RNA RISC RNA-induced silencing complex FCMD Fukuyama muscular dystrophy NAHR non-allelic homologous recombination IR inverted repeat DSB double strand break TIR terminal inverted repeat miSAT minor satellite ENC evolutionary new centromere HOR higher order array CR centromeric retroelement S. J. Klein, R. J. O’Neill CRR LAVA KERV Tal1 crasiRNAs KRAB KZFP ES TRIM28 HAC centromeric retroelement of rice LINE-ALU-VNTR-ALU like kangaroo endogenous retrovirus transposon of Arabidopsis lyrata 1 centromere repeat-associated short interacting RNAs Krüppel-associated box KRAB-zinc finger protein embryonic stem tripartite motif containing 28 human artificial chromosome Introduction Transposable elements (TE) are segments of DNA that can move, or transpose, within the genome. The existence of elements capable of intragenomic mobility was first discovered in maize by American scientist Barbara McClintock in the 1940s and described in her seminal 1950 paper (McClintock 1950). Originally dismissed as an obscure observation, McClintock’s work was eventually recognized as groundbreaking, challenging the view of the genome as a static unit of heritability, and leading to the emergence of the concept of the Bdynamic genome.^ Following McClintock’s discovery, TEs were viewed merely as Bjunk DNA^ and Bselfish DNA parasites,^ simple sequences that multiply within the genome yet provide no apparent beneficial contribution to its host (Doolittle and Sapienza 1980; Orgel and Crick 1980). However, genome-scale studies over the past several decades have shown that TEs play a key role in genome function, chromosome evolution, speciation, and diversity. The Human Genome Project revealed just how abundant TEs are in humans, making up approximately 45% of the overall human genome content (Cordaux and Batzer 2009; Lander et al. 2001). TEs can be divided into two major classes based on transposition mechanism: DNA transposons, which move via a Bcut-and-paste^ mechanism and RNA transposons, also referred to as retrotransposons or retroelements, which move via a Bcopy-and-paste^ mechanism. Retroelements can then be further subdivided into long terminal repeat elements (LTRs), including retroviruses, and non-LTR elements. While there is no evidence for DNA transposon activity in humans in the past 50 million years (Lander et al. 2001), some retroelements are still active today, including members of the non-LTR class of retroelements, namely long interspersed nuclear elements (LINEs), short interspersed nuclear elements (SINEs), SINE-VNTR-Alu elements (SVAs) (Mills et al. 2007), and potentially members of the LTR-class of endogenous retroviruses (HERVs). LINEs are considered the only autonomous nonLTR TE in humans since these TEs encode all of the components required for transposition, while SINEs and SVAs are considered non-autonomous as these elements require the presence of another active TE to mobilize (Dewannieux et al. 2003). Within the LINE and SINE retroelement classes in humans, two distinct families stand out: LINE1 and Alu, respectively. LINE1s, the only remaining mobile LINE family in humans, constitutes ~ 17–20% of the human genome (Lander et al. 2001). Alus, the active and mobile SINE family in humans, constitutes a smaller portion of the human genome (~ 11%) by nucleotide count, yet are more abundant in copy number than LINE1s due to their 20-fold smaller element size (Cordaux and Batzer 2009; Quentin 1992; Roy-Engel et al. 2002). In contrast to LINE1 and Alu, SVAs only make up ~ 0.2% of the human genome (Cordaux and Batzer 2009; Wang et al. 2005). A caveat to the observation that mobile TEs in humans are restricted to LINE1s, Alus, and SVAs was recently discovered when members of the human endogenous retrovirus family HERV-Ks, also known as HML2s (~ 1% of the human genome (Subramanian et al. 2011)), were found to contain full, intact open reading frames and were identified in polymorphic sites in the human population, implicating recent, if not retained, mobility (Belshaw et al. 2005; Belshaw et al. 2004; Dewannieux et al. 2006; Hughes and Coffin 2004). With rare exceptions, TEs are found in the genomes of nearly all eukaryotic species. However, the TE composition within the genome and the types of active elements are highly variable among species (see Huang et al. 2012 and Sotero-Caio et al. 2017 for reviews). This review focuses on the impact of TEs on chromosome function and evolution, with an emphasis on the human genome and the retroelements that retain the capacity to mobilize. Furthermore, this review examines the contri (...truncated)