Random sequences are an abundant source of bioactive RNAs or peptides

Abstract

It is generally assumed that new genes arise through duplication and/or recombination of existing genes. The probability that a new functional gene could arise out of random non-coding DNA is so far considered to be negligible, as it seems unlikely that such an RNA or protein sequence could have an initial function that influences the fitness of an organism. Here, we have tested this question systematically, by expressing clones with random sequences in Escherichia coli and subjecting them to competitive growth. Contrary to expectations, we find that random sequences with bioactivity are not rare. In our experiments we find that up to 25% of the evaluated clones enhance the growth rate of their cells and up to 52% inhibit growth. Testing of individual clones in competition assays confirms their activity and provides an indication that their activity could be exerted by either the transcribed RNA or the translated peptide. This suggests that transcribed and translated random parts of the genome could indeed have a high potential to become functional. The results also suggest that random sequences may become an effective new source of molecules for studying cellular functions, as well as for pharmacological activity screening.

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Figure 1: Induction of expression through IPTG drives changes in clone frequency over time.
Figure 2: Examples of four clones with significant changes in frequency over time.
Figure 3: Assessment of read depth on detection power.
Figure 4: Expression of peptides.
Figure 5: Growth competition experiment with three selected clones.

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Acknowledgements

We thank S. Künzel for sequencing and E. Özkurt for contributions during her rotation project. The project was financed through an ERC advanced grant to D.T. (NewGenes—322564).

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R.N. and D.T. designed the experiment, C.A. constructed the library, C.A., B.Y. and E.M. conducted the experiments, R.N. did the bioinformatic analysis, and R.N. and D.T. wrote the paper.

Corresponding author

Correspondence to Diethard Tautz.

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Competing interests

The work described in this publication is subject to patent application by the Max-Planck Society.

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Supplementary Table 1 (XLSX 116 kb)

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Neme, R., Amador, C., Yildirim, B. et al. Random sequences are an abundant source of bioactive RNAs or peptides. Nat Ecol Evol 1, 0127 (2017). https://doi.org/10.1038/s41559-017-0127

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