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Review
. 2013 Jun;30(6):1239-51.
doi: 10.1093/molbev/mst045. Epub 2013 Mar 13.

Exaptation of transposable elements into novel cis-regulatory elements: is the evidence always strong?

Flávio S J de Souza  1 , Lucía F Franchini, Marcelo Rubinstein
Affiliations
Review

Exaptation of transposable elements into novel cis-regulatory elements: is the evidence always strong?

Flávio S J de Souza et al. Mol Biol Evol. 2013 Jun.

Abstract

Transposable elements (TEs) are mobile genetic sequences that can jump around the genome from one location to another, behaving as genomic parasites. TEs have been particularly effective in colonizing mammalian genomes, and such heavy TE load is expected to have conditioned genome evolution. Indeed, studies conducted both at the gene and genome levels have uncovered TE insertions that seem to have been co-opted--or exapted--by providing transcription factor binding sites (TFBSs) that serve as promoters and enhancers, leading to the hypothesis that TE exaptation is a major factor in the evolution of gene regulation. Here, we critically review the evidence for exaptation of TE-derived sequences as TFBSs, promoters, enhancers, and silencers/insulators both at the gene and genome levels. We classify the functional impact attributed to TE insertions into four categories of increasing complexity and argue that so far very few studies have conclusively demonstrated exaptation of TEs as transcriptional regulatory regions. We also contend that many genome-wide studies dealing with TE exaptation in recent lineages of mammals are still inconclusive and that the hypothesis of rapid transcriptional regulatory rewiring mediated by TE mobilization must be taken with caution. Finally, we suggest experimental approaches that may help attributing higher-order functions to candidate exapted TEs.

Keywords: enhancer; exaptation; gene expression; mobile element.

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Figures

F<sc>ig</sc>. 1.
Fig. 1.
Scheme of vertebrate phylogenetic tree showing well-characterized transposable elements (TE)-exaptation events into enhancers and insulators. Different TE exaptation events are indicated with different colors. Circles indicate the branch where the corresponding TE subfamily originated and/or diversified before exaptation, whereas filled circles indicate the branch where a particular TE instance was exaptated as a regulatory element. References for TE origins are LF-SINE, Bejerano et al. (2006); AmnSINE, Sasaki et al. (2008); MIR/CORE-SINE, Gilbert and Labuda (1999, 2000); mammalian apparent LTR (MaLR), Smit (1993); ERV9, Costas and Naveira (2000); and B2 SINE, Churakov et al. (2010). Other references can be found in table 1. Branches not drawn to scale.
F<sc>ig</sc>. 2.
Fig. 2.
Scheme of a mouse embryo at approximately 11 days of gestation showing the expression patterns driven by well-characterized, TE-derived enhancers. Expression territories of each gene and some anatomical features are indicated. See text and table 1 for references and details.
F<sc>ig</sc>. 3.
Fig. 3.
Scheme of the evolution of new TFBS in the vicinity of genes. Primitively, a hypothetical gene (pink oval) is controlled by a set of three TFBS (blue circle, green pentagon, and yellow square). 1) New sites may appear in the vicinity by random mutation, possibly leading to turnover of previously present TFBS (green pentagon) or a new TFBS appearing (violet square). 2) Alternatively, the insertion of a TE nearby initially has no influence on transcription, but random mutation leads to TFBS turnover and/or new TFBS. Some sites might be just a few mutations from acquiring functionality (presites). 3) In some instances, a TE carrying functional TFBS may insert near a promoter, leading to an immediate change in transcription. TE-derived TFBS may eventually cause turnover of primitive TFBS.
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