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

de Souza FS, Franchini LF, Rubinstein M - Mol. Biol. Evol. (2013)

Bottom Line: TEs have been particularly effective in colonizing mammalian genomes, and such heavy TE load is expected to have conditioned genome evolution.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.Finally, we suggest experimental approaches that may help attributing higher-order functions to candidate exapted TEs.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina. fsouza.ingebi@gmail.com

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.

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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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mst045-F3: 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.

Mentions: As evolutionary time goes by, new TF-binding motifs are expected to appear in promoters or enhancers by random mutation. These new motifs can be eventually lost from the population, become fixed by genetic drift or, in case they have a large positive effect on fitness, might be kept by natural selection (Lynch 2007). New motifs may also replace pre-existent ones (turnover) by stabilizing selection, without significantly changing the expression of the gene (Ludwig 2002). In this context, TEs might contribute to the birth of new transcriptional regulatory elements using two alternative routes (fig. 3):-


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

de Souza FS, Franchini LF, Rubinstein M - Mol. Biol. Evol. (2013)

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.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3649676&req=5

mst045-F3: 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.
Mentions: As evolutionary time goes by, new TF-binding motifs are expected to appear in promoters or enhancers by random mutation. These new motifs can be eventually lost from the population, become fixed by genetic drift or, in case they have a large positive effect on fitness, might be kept by natural selection (Lynch 2007). New motifs may also replace pre-existent ones (turnover) by stabilizing selection, without significantly changing the expression of the gene (Ludwig 2002). In this context, TEs might contribute to the birth of new transcriptional regulatory elements using two alternative routes (fig. 3):-

Bottom Line: TEs have been particularly effective in colonizing mammalian genomes, and such heavy TE load is expected to have conditioned genome evolution.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.Finally, we suggest experimental approaches that may help attributing higher-order functions to candidate exapted TEs.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina. fsouza.ingebi@gmail.com

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.

Show MeSH