The Birth of Introns

Eukaryotic genes are composed of exons and introns. Introns are non-coding sequences that separate the coding exons, and are spliced out of the pre-messenger RNA after transcription. This modular structure of eukaryotic genes allows alternative splicing, by which single genes can encode multiple isoforms of proteins, hence widening the diversity of the proteome. Introns also have important roles in genetic regulation; for instance as sites of enhancers, and by encoding microRNAs.

Intron position is often conserved between orthologous eukaryotic genes showing that spliceosomal introns originated early in eukaryotic evolution. However, it has been difficult to explain the mechanisms of intron loss, and especially, gain that have maintained a high number of introns in present day eukaryotic genomes. Current models suggest that introns should be being lost faster than they are gained. However, studies in organisms such as the urochordate, Oikopleura dioca, and the green alga, Micromonas pusilla, have shown extensive recent intron gains. Interestingly, the study of the Micromonas genome discovered a form of intronic repeat sequence that ‘extended nearly to donor and acceptor sites, and lacked known TE (transposable element) characteristics’. These sequences were termed ‘Introner elements’. A new study, forthcoming in Current Biology, has discovered and characterised something similar in various fungal clades.

Burgt et al. found numerous introns with near-identical sequences in the Dothidiomycete fungus Cladosporium fulvum. They then widened their analysis to search for similar introns in the ‘intronomes’ of 23 other species of fungi, and found large sets of near-identical introns in 6 different species. Phylogenetic analyses of these ‘introner-like elements’ (ILEs) showed that they could be grouped into related clusters, and that in turn the clusters were related to each other, indicating that all the ILE clusters were derived from a single ancestral element.

Analysis of the molecular structure of the Introner-like elements showed that they contained all the distinguishing features of normal spliceosomal introns, such as splice acceptor and donor sites, and branch point sequences. ILEs were longer than normal introns, and were found to fold into more stable secondary structures. Burgt et al. suggest that these predicted stable secondary structures are likely to have important functions, as they observed compensatory mutations that conserve secondary structure between related ILEs.

Analysing intron gain in the 6 species of fungi in which they found ILEs, Burgt et al find that ILEs account for the majority of recent gains. In closely related sister species that diverged within the last 22,000 years ILEs account for 90% of intron gains, but this figure rapidly drops off for older divergences. This leads Burgt et al. to consider that most intron gains are due to ILE multiplication, with rapid degeneration meaning that ILE identification becomes progressively more difficult.

Introner-like elements therefore appear to be mobile elements that can in some way transpose to new sites leading to intron gain. Just what mechanism is employed in this process is far from clear. Many different mechanisms for intron gain have been proposed but as yet there is little experimental evidence demonstrating that they occur in vivo. These include Intron transposition, in which an intron transposes to a new position in a transcript, which is then reverse transcribed and recombined into the original gene; Transposon insertion in which a transposon becomes a spliceable intron; Intronisation in which exons are converted into intron by accumulated mutation; and other ideas based on genetic duplications and errors during repair processes. Burgt et al think that the most likely mechanism for ILEs is a process by which introns are reverse spliced directly into the genome and then reverse transcribed. It will be interesting to see whether ILE transposition can be observed in vivo and figure out just what mechanism of intron generation is employed.

Interestingly, introner-like elements differ from the introner elements found in Micromonas in important ways. Introner elements were found within introns rather than being the whole intron, and lacked the interesting secondary structures observed in ILEs. Along with the author’s inability to find ILEs in other clades, this suggests that ILEs may not be a very widespread mechanism of intron multiplication. However Burgt et al. disagree, and reckon that ILEs could potentially be an ancestral mechanism for intron gain.

van der Burgt, A., Severing, E., de Wit, P., & Collemare, J. (2012). Birth of New Spliceosomal Introns in Fungi by Multiplication of Introner-like Elements Current Biology DOI: 10.1016/j.cub.2012.05.011

One response to “The Birth of Introns

  1. Very interesting webpage. Two things however have surprised me:
    At first, Introners are far to be only located in introns. This is easy to verify. Look at the positions of the three introners in ORFs at http://genome.jgi-psf.org/cgi-bin/browserLoad/?db=MicpuC3&position=scaffold_1:40000-50000.
    Second, you should sample micromonas introner sequences in database and investigate their structure in RNA Mfold. I found them rather structured with compensatory pairs of mutations.
    I agree, these two points are not described in these terms in the reference Science paper, but the observation show that inaccurate points are given in this paper about these elements.
    Best regards
    Yves

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