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No evidence of functional co-adaptation between clustered microRNAs

View ORCID ProfileAntonio Marco
doi: https://doi.org/10.1101/274811
Antonio Marco
University of Essex
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Abstract

A significant fraction of microRNA loci are organized in genomic clusters. The origin and evolutionary dynamics of these clusters have been extensively studied, although different authors have come to different conclusions. In a recent paper, it has been suggested that microRNAs in the same clusters evolve to target overlapping sets of genes. The authors interpret this as functional co-adaptation between clustered microRNAs. Here I reanalyze their results and I show that the observed overlap is mostly due to two factors: similarity between two seed sequences of a pair of clustered microRNAs, and the expected high number of common targets between pairs of microRNAs that have a large number of targets each. After correcting for these factors, I observed that clustered microRNAs from different microRNA families do not share more targets than expected by chance. During an exchange of correspondence and manuscripts, the authors of the original report acknowledged that the permutation methods they performed was not the method they described in their original paper. Here I show that the new permutation test proposed is biased and leads to systematic errors of the first kind, which will explain why the p-values reported were extremely (and unrealistically) low. I also discuss how to investigate the evolutionary dynamics of clustered microRNAs and their targets. In conclusion, there is no evidence of widespread functional co-adaptation between clustered microRNAs.

Footnotes

  • In this revision I corrected a bug in one of the programs and updated the manuscript accordingly. The results remained unaltered. Additionally I added some discussion on a topic raised by other authors regarding non-conserved targets, which turned out to support the model I proposed earlier. NOTE FROM PREVIOUS REVISION: The previous version has a response in which the authors acknowledge that a different method was used in their original analysis. In this version I reproduce the new methodology and show why it leads to incorrect p-values.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 17, 2019.
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No evidence of functional co-adaptation between clustered microRNAs
Antonio Marco
bioRxiv 274811; doi: https://doi.org/10.1101/274811
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No evidence of functional co-adaptation between clustered microRNAs
Antonio Marco
bioRxiv 274811; doi: https://doi.org/10.1101/274811

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